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At least 343 records · Page 19Linked to original sources
PubMed2005

Molecular mechanisms in cancer: what should clinicians know?

Normal cells are influenced by a variety of environmental and host influences that can produce pro-carcinogenic mutations. Either a single or a series of mutations might result in cellular transformation. Like normal cells, most cancer cells use multiple redundant intracellular signaling pathways to ensure the maintenance and viability of functions critical to their survival. Thus, cellular pathways that are integral to cell function, survival, proliferation, and receptor expression are potential targets for therapeutic intervention. One example of this is the epidermal growth factor receptor signaling pathway. Other potential targets are molecules that mediate processes through which tumors produce angiogenic and invasion factors that stimulate host blood vessel growth into tumors and allow tumor growth and metastasis, such as the vascular endothelial growth factor. Targeting of downstream events that result in cellular apoptosis is another potential strategy. Continued investigations may result in the development of proteomic profiling databases through which a patient might be matched with molecular signatures in a library and upon which individualized cancer therapies might be selected. In this way, clinicians might recommend combinations of molecularly targeted agents and other therapies on the basis of an individual patient's proteomic profile.

Humans↗
PubMed2026

Decoding protein signatures and protein interactions in oral potentially malignant disorders: a systematic review and network analysis.

BACKGROUND: Proteomic profiling offers thorough insights into protein structure and function, as well as it acts as an essential approach for analyzing molecular changes at the tissue level. However, because of the proteome's diversity and dynamic nature, biomarker discovery remains challenging. By combining proteomics with bioinformatics, the level of understanding in relation to molecular interactions and disease processes can be improved. Through an integrative approach, few limitations can be addressed, thereby promoting proteomic profiling for the discovery of new therapeutic targets and novel biomarkers for a variety of disorders. AIM: To identify differentially expressed protein markers and their key molecular pathways associated with Oral Potentially Malignant Disorders. METHODS: Systematic Review was conducted following the PRISMA guidelines and the protocol registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the registration ID number CRD42024557545. A comprehensive literature review was performed using electronic databases, yielding 12,797, studies from which 15 eligible articles were selected. The Newcastle-Ottawa Scale was used to assess the risk of bias. Vote counting was performed to identify proteins reported in more than one study. A bipartite network was constructed using Cytoscape to identify shared and disease-specific protein markers. Lesion-wise protein-protein interaction networks were generated using STRING and analysed in Cytoscape to identify highly interconnected hub proteins, and pathway enrichment analysis for these hubs was performed using Reactome. RESULTS: A total of fifteen studies (Leukoplakia (LK) - n = 1, Proliferative Verrucous Leukoplakia (PVL) - n = 2, Oral Submucous Fibrosis (OSMF) - n = 7, and Oral Lichen Planus (OLP) - n = 5) were included. The Newcastle-Ottawa Scale was used to evaluate methodological quality and the quality of studies included in this systematic review was high for 4 articles and moderate in the remaining 11. The most commonly employed technique was mass spectrometry. A total of 318 candidate proteins (LK - 14, PVL - 82, OSMF - 172, and OLP - 50) were identified across the oral potentially malignant disorders. Key markers identified through vote counting included ERO1A, NUCB1, RHOA, and IL36A for PVL; LUM, KRT1, KRT9, ALB, and VIM for OSMF; and ALB, LYZ, HP, HBB, and AMY1A for OLP. The bipartite network showed that OSMF and OLP shared the highest number of proteins, indicating the strongest overlap among lesions. Network analysis further highlighted distinct hub proteins for each lesion: for LK- AMY1A, AMY1B and APOA1; for PVL- CFL1, RHOA and CDC42; for OSMF- HSP90AA1, ENO1 and SERPINA1; and for OLP- HP, B2M, and ORM1. Lesion-specific pathway enrichment revealed that LK was associated with epithelial differentiation, PVL with oncogenic signaling, OSMF with stress-driven fibrosis, and OLP with immune-mediated inflammation. CONCLUSIONS: Proteomic expression offers insights into disease pathogenesis by identifying important molecular changes across OPMDs. However, the majority of biomarkers are still in the exploratory stage due to the considerable variation in lesion types, sample sources, proteomic techniques, and reporting systems. In order to create reliable and clinically applicable biomarkers, future studies should concentrate on combining multi-omics techniques with large-scale, standardized cohorts.

Humans↗
PubMed2025

Multi-omic integration with human dorsal root ganglia proteomics highlights TNFα signalling as a relevant sexually dimorphic pathway.

The peripheral nervous system (PNS) plays a critical role in pathological conditions, including chronic pain disorders, that manifest differently in men and women. To investigate this sexual dimorphism at the molecular level, we integrated quantitative proteomic profiling of human dorsal root ganglia (hDRG) and peripheral nerve tissue into the expanding omics framework of the PNS. Using data-independent acquisition (DIA) mass spectrometry, we characterized a comprehensive proteomic profile, validating tissue-specific differences between the hDRG and peripheral nerve. Through multi-omic analyses and in vitro functional assays, we identified sex-specific molecular differences, with TNFα signalling emerging as a key sexually dimorphic pathway with higher prominence in men. Genetic evidence from genome-wide association studies further supports the functional relevance of TNFα signalling in the periphery, while clinical trial data and meta-analyses indicate a sex-dependent response to TNFα inhibitors. Collectively, these findings underscore a functionally sexual dimorphism in the PNS, with direct implications for sensory and pain-related clinical translation.

Humans↗
PubMed2007

A proteomic analysis of adult rat bone reveals the presence of cartilage/chondrocyte markers.

The non-mineral component of bone matrix consists of 90% collagenous, 10% non-collagenous proteins. These proteins regulate mineralization, growth, cell signaling and differentiation, and provide bone with its tensile strength. Expression of bone matrix proteins have historically been studied individually or in small numbers owing to limitations in analytical technologies. Current mass-spectrometric and separations technologies allow a global view of protein expression patterns in complex samples. To our knowledge, no proteome profile of bone matrix has yet been reported. Therefore, we have used mass spectrometry as a tool to generate a profile of proteins present in the extracellular matrix of adult rat bone. Overall, 108 and 25 proteins were identified with high confidence in the metaphysis and diaphysis, respectively, using a bottom up proteomic technique. Twenty-one of these proteins were present in both the metaphysis and diaphysis including the bone specific proteins, osteocalcin, type I collagen, osteopontin, osteoregulin, and bone sialoprotein. Interestingly, type II collagen, a protein thought to be exclusively expressed in cartilage, was identified in both the metaphysis and diaphysis. This observation was validated by Western blot. Additionally, the presence of aggrecan, another protein expressed in cartilage was identified in the bone matrix extracts by Western blot. The proteome profile generated using this technology represents an initial survey of the acid soluble proteins of bone matrix which provides a reference for the analysis of deviations from the normal composition due to perturbations or disease states.

Aggrecans↗
PubMed2002

The SELDI-TOF MS approach to proteomics: protein profiling and biomarker identification.

The need for methods to identify disease biomarkers is underscored by the survival-rate of patients diagnosed at early stages of cancer progression. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) is a novel approach to biomarker discovery that combines two powerful techniques: chromatography and mass spectrometry. One of the key features of SELDI-TOF MS is its ability to provide a rapid protein expression profile from a variety of biological and clinical samples. It has been used for biomarker identification as well as the study of protein-protein, and protein-DNA interaction. The versatility of SELDI-TOF MS has allowed its use in projects ranging from the identification of potential diagnostic markers for prostate, bladder, breast, and ovarian cancers and Alzheimer's disease, to the study of biomolecular interactions and the characterization of posttranslational modifications. In this minireview we discuss the application of SELDI-TOF MS to protein biomarker discovery and profiling.

Biomarkers, Tumor↗
PubMed2005

Novel molecular signaling and classification of human clinically nonfunctional pituitary adenomas identified by gene expression profiling and proteomic analyses.

Pituitary adenomas comprise 10% of intracranial tumors and occur in about 20% of the population. They cause significant morbidity by compression of regional structures or the inappropriate expression of pituitary hormones. Their molecular pathogenesis is unclear, and the current classification of clinically nonfunctional tumors does not reflect any molecular distinctions between the subtypes. To further elucidate the molecular changes that contribute to the development of these tumors and reclassify them according to the molecular basis, we investigated 11 nonfunctional pituitary adenomas and eight normal pituitary glands, using 33 oligonucleotide GeneChip microarrays. We validated microarray results with the reverse transcription real-time quantitative PCR, using a larger number of nonfunctional adenomas. We also used proteomic analysis to examine protein expression in these nonfunctional adenomas. Microarray analysis identified significant increases in the expression of 115 genes and decreases in 169 genes, whereas proteomic analysis identified 21 up-regulated and 29 down-regulated proteins. We observed changes in expression of SFRP1, TLE2, PITX2, NOTCH3, and DLK1, suggesting that the developmental Wnt and Notch pathways are activated and important for the progression of nonfunctional pituitary adenomas. We further analyzed gene expression profiles of all nonfunctional pituitary subtypes to each other and identified genes that were affected uniquely in each subtype. These results show distinct gene and protein expression patterns in adenomas, provide new insight into the pathogenesis and molecular classification of nonfunctional pituitary adenomas, and suggest that therapeutic targeting of the Notch pathway could be effective for these tumors.

Adenoma↗
PubMed2005

Multidimensional protein identification technology: current status and future prospects.

Protein profiling using high-throughput tandem mass spectrometry has become a powerful method for analyzing changes in global protein expression patterns in cells and tissues as a function of developmental, physiologic and disease processes. This review summarizes the utility and practical application of multidimensional protein identification technology as a platform for comprehensive proteomic profiling of complex biologic samples. The strengths and potential problems and limitations associated with this powerful technology are discussed, with an emphasis placed on one of the biggest challenges currently facing large-scale expression profiling projects -- namely, data analysis. Complementary bioinformatic computational data mining strategies, such as clustering, functional annotation and statistical inference, are also discussed as these are increasingly necessary for interpreting the results of global proteomic profiling studies.

Animals↗
PubMed2006

An integrated map of the murine hippocampal proteome based upon five mouse strains.

With the advent of proteomics technologies it is possible to simultaneously demonstrate the expression of hundreds of proteins. The information offered by proteomics provides context-based understanding of cellular protein networks and has been proven to be a valuable approach in neuroscience studies. The mouse hippocampus has been a major target of analysis in the search for molecular correlates to neuronal information storage. Although human and rat hippocampal samples have been successfully subjected to proteomic profiling, no elaborate analysis providing the fundamental experimental basis for protein-expression studies in the mouse hippocampus has been carried out as yet. This led us to construct a master map generated from the individual hippocampal proteomes of five different mouse strains. A proteomic approach, based upon 2-DE coupled to MS (MALDI-TOF/TOF) has been chosen in an attempt to establish a comprehensive reference database of proteins expressed in the mouse hippocampus. 469 individual proteins, represented by 1156 spots displaying various functional states of the respective gene products were identified. Proteomic profiling of the hippocampus, a brain region with a pivotal role for neuronal information processing and storage may provide insight into the characteristics of proteins serving this highly sophisticated function.

Animals↗
PubMed2025

Stage-dependent proteomic alterations in aqueous humor of diabetic retinopathy patients based on data-independent acquisition and parallel reaction monitoring.

BACKGROUND: Diabetic retinopathy (DR), a microvascular complication of diabetes mellitus (DM), represents the predominant cause of preventable vision loss in working-age populations globally. While the pathophysiological mechanisms underlying DR progression remain incompletely understood, our study employs comprehensive proteomic profiling of aqueous humor (AH) to identify stage-specific biomarkers and therapeutic targets in type 2 diabetes mellitus (T2DM) patients across DR progression. METHODS: Utilizing data-independent acquisition (DIA) mass spectrometry, we quantified AH proteomes in a discovery cohort comprising 24 subjects: 18 T2DM patients stratified by DR severity [6 non-DR, 6 non-proliferative DR (NPDR), 6 proliferative DR (PDR)] and 6 cataract controls without diabetes (non-DM). Validation cohort analysis (including 10 AH samples in each group) was performed using parallel reaction monitoring (PRM) strategy for verification of target proteins. Comprehensive bioinformatics analyses included gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) network construction, receiver operating characteristic (ROC) curve analysis, and ConnectivityMap (Cmap)-based drug prediction. RESULTS: Proteomic profiling identified 739 quantifiable AH proteins (62% extracellular) with clear separation among the four clinical stages in the discovery cohort. GSEA uncovered altered expression of proteins mainly related to complement and coagulation cascades, folate metabolism, and the selenium micronutrient network in patients with DR. WGCNA-derived protein modules yielded 83 PRM-validated targets, including 5 hub proteins differentiating NPDR from non-DR and 33 hub proteins showed significant upregulation in PDR versus NPDR comparison. Clinical correlation analysis identified F2, FGG, FGB, RBP4, AMBP, VTN, C8A, CPB2, and C2 associated with clinical traits. C6, FAM3C, SPP1, and JCHAIN levels were altered post-anti-VEGF treatment. Pharmacological prediction identified potential therapeutic compounds, including perindopril, triciribine, and XAV-939 for NPDR, and topiramate, triciribine, and vecuronium for PDR. CONCLUSION: This study established a comprehensive AH proteomic signature of DR progression, offering insights into the pathogenesis of DR and highlighting potential biomarkers and novel therapeutic targets.

Humans↗
PubMed2006

Identification of a plasma proteomic signature to distinguish pediatric osteosarcoma from benign osteochondroma.

Osteosarcoma (OS) is the most common malignant bone tumor in children. To identify a plasma proteomic signature that can detect OS, we used SELDI MS to perform proteomic profiling on plasma specimens from 29 OS and 20 age-matched osteochondroma (OC) patients. Nineteen statistically significant ion peaks that were differentially expressed in OS when compared with OC patients were identified (p < 0.001 and false discovery rate < 10%). Using the proteomic profiles, we constructed a multivariate 3-nearest neighbors classifier to distinguish OS from OC patients with a sensitivity of 97% and a specificity of 80% based on external leave-one-out crossvalidation. Permutation test showed that the classification result was statistically significant (p < 0.00005). One of the proteins (m/z 11 704) in the proteomic signature was identified as serum amyloid protein A (SAA) by PMF. The higher plasma level of SAA in OS patients was further validated by Western blotting when compared to that of osteochrondroma patients and normal subjects as reference. The classifier based on this plasma proteomic signature may be useful to differentiate malignant bone cancer from benign bone tumors and for early detection of OS in high-risk individuals.

Adolescent↗
PubMed2026

Cryopreservation-induced proteomic alterations in P&#xea;ga donkey (Equus asinus) spermatozoa.

Semen cryopreservation is a key tool for assisted reproduction and genetic conservation, but its efficiency remains limited in donkeys, compromising post-thaw sperm quality. This study aimed to characterize the proteomic profile of P&#xea;ga donkey spermatozoa and to investigate molecular mechanisms associated with cryopreservation-induced impairment of sperm function. Semen samples were collected from P&#xea;ga jacks and evaluated for sperm motility and vigor before and after cryopreservation. Quantitative proteomic analysis was performed by LC-MS/MS, followed by bioinformatic characterization of differentially abundant proteins. Cryopreservation markedly reduced sperm motility in all animals, whereas sperm vigor showed only a non-significant tendency toward reduction, suggesting sublethal cryoinjury primarily affecting flagellar efficiency. Proteomic profiling identified 554 proteins, of which 98 were differentially abundant between in natura and cryopreserved spermatozoa. Functional enrichment analyses showed that these proteins were mainly associated with energy metabolism, mitochondrial oxidative phosphorylation, glycolysis, cytoskeletal organization, signal transduction, proteostasis, and oxidative stress response. Notably, proteins involved in ATP production, mitochondrial function, and axonemal organization were significantly altered, supporting a mechanistic link between metabolic dysfunction, flagellar structural disorganization, and reduced post-thaw motility. Overall, cryopreservation induced coordinated and compartment-specific remodeling of the donkey sperm proteome, particularly affecting pathways essential for motility and functional competence. These findings provide new molecular insights into the cryobiological vulnerability of donkey spermatozoa and establish a mechanistic basis for the development of more effective, biology-driven cryopreservation strategies for this species.

Animals↗
PubMed2004

Preparation of planar retinal specimens: verification by histology, mRNA profiling, and proteome analysis.

PURPOSE: Elucidation of the transcriptome and proteome of the normal retina will be difficult since it is comprised of at least 55 different cell types. However the characteristic layered cellular anatomy of the retina makes it amenable to planar sectioning, enabling the generation of enriched retinal cell populations. The aim of this study was to validate a reproducible method for preparing enriched retinal layers from porcine retina. METHODS: The thicknesses of the retinal photoreceptor, inner nuclear and ganglion cell, and fiber layers were determined by routine histology of cross sections of fresh whole retina mounted on polyvinylidene difluoride (PVDF) membrane. Dissected retina (5 mm2) was placed on PVDF membrane and a series of planar cryosections corresponding to the photoreceptor and inner nuclear layer were removed leaving the ganglion cell and fiber layer which was subsequently detached from the membrane. The retinal specimens were stored at -80 degrees C. Representative planar tissue sections were sonicated in ice-chilled 40 mM ammonium bicarbonate pH 7.9 and aliquots removed for RNA extraction. Quantitative RT-PCR was used to analyze the mRNA expression of genes indicative of specific retinal layers. Ammonium bicarbonate protein extracts were centrifuged, lyophilized and prepared for direct liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using a Waters Q-Tof Ultima. RESULTS: Histological analysis established the parameters for planar cryosectioning: photoreceptor layer (69+/-1.8 microm), outer plexiform (11+/-0.6 microm), inner nuclear layer (28+/-0.5 microm), inner plexiform, ganglion cell and fiber layer (100+/-5.3 microm). Gene expression profiling provided an independent method for validating the respective retinal preparations. For example, glial fibrillary acidic protein (GFAP) was expressed up to 21 fold higher in the inner retinal "ganglion cell enriched" fraction than in the outer retinal "photoreceptor enriched" fraction. The pattern was reversed for blue cone opsin, which was expressed up to 24 fold higher in the "photoreceptor enriched" fraction. Endogenous protein fragments indicative of each layer were identified by mass spectrometry and de novo sequence data obtained. CONCLUSIONS: Combined histological and mRNA expression profiling has confirmed the development of a reproducible method for generating validated porcine retinal layers enriched for specific cell types. Direct proteome analysis detected endogenous peptide fragments of characteristic retinal proteins. Further analysis of these enriched retinal cell preparations will facilitate a more selective investigation of the retinal transcriptome and proteome than studies of the intact retina.

Anatomy, Cross-Sectional↗
PubMed2006

Proteomic analysis of suction blister fluid isolated from human skin.

The regulation of cutaneous immune responses in health and disease is mediated locally by proteins such as cytokines and chemokines. We used a novel approach involving proteomic profiling of fluid drawn from suction blisters to compare and contrast protein expression in normal skin with that in nonlesional skin from a patient with plaque psoriasis. We also examined the impact of exogenous interleukin-1beta, a proinflammatory cytokine, on protein expression in these tissues. Described here are the results of proteomic profiling of 670 proteins from blister fluid, and the identification by differential expression of nine proteins between one volunteer with psoriasis and one normal volunteer. Although the apparent disease association of these nine proteins will require validation using additional volunteers, the identification of candidate protein biomarkers through proteomic analyses of blister fluid represents a promising approach for monitoring the disease activity and efficacy of therapeutic intervention in human skin diseases.

Biomarkers↗
PubMed2005

Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells.

OBJECTIVES: Paclitaxel (Taxol), a potent drug of natural origin isolated from the bark of the Pacific yew, is widely used in the treatment of ovarian, lung and breast cancer. At present, there is little information regarding the anti-cancer mechanism of paclitaxel against cervical carcinoma cells. We thus tried to show the anti-cancer effect of paclitaxel on cervical carcinoma cell line carrying HPV by using a proteomic analysis and to investigate the mechanism of actions. METHODS: We treated paclitaxel to cervical carcinoma cells and then carried out MTT assay to observe the anti-proliferate activity. Using proteomics analysis including two-dimensional (2-DE) gel electrophoresis and MALDI-TOF-MS, we tried to find the anti-proliferate activity-related proteins. Among them, paclitaxel treatment suppressed the expression of the mitotic checkpoint protein BUB3. Functional proteomic analysis by small interfering RNA (siRNA) targeting was tried to illuminate a role of mitotic checkpoint protein BUB3 in cell cycle progression. RESULTS: The cytotoxicity effects of paclitaxel were determined in HPV-16 positive CaSki, HPV-18 positive HeLa and HPV-negative C33A cervical carcinoma cell lines. Using efficient proteomics methods including 2-DE/MALDI-TOF-MS, we identified several cellular proteins that are responsive to paclitaxel treatment in HeLa cells. Paclitaxel treatment elevated mainly apoptosis-related, immune response-related and cell cycle check point-related proteins. On the other hand, paclitaxel treatment diminished growth factor/oncogene-related proteins and transcription regulation-related proteins. Paclitaxel showed anti-proliferate activity through the membrane death receptor (DR)-mediated apoptotic pathway involving activation of caspase-8 with a TRAIL-dependent fashion as well as the mitochondrial-mediated pathway involving down-regulation of bcl-2 by cytochrome c release. Furthermore, we found siRNA-induced BUB3 knock down on cell cycle progression blocked by cell cycle arrest after paclitaxel treatment. CONCLUSIONS: The proteome profiling technique provided a broad-base and effective approach for the identification of protein changes induced by paclitaxel and showed anti-proliferate activity through the membrane death receptor-mediated apoptotic pathway, the mitochondrial-mediated pathway. This study shows the power of proteomic profiling with functional analysis using RNAi technology for the discovery of novel molecular targets and a better understanding of the actions of paclitaxel at the molecular level in cervical carcinoma cells.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Signal in noise: evaluating reported reproducibility of serum proteomic tests for ovarian cancer.

Proteomic profiling of serum initially appeared to be dramatically effective for diagnosis of early-stage ovarian cancer, but these results have proven difficult to reproduce. A recent publication reported good classification in one dataset using results from training on a much earlier dataset, but the authors have since reported that they did not perform the analysis as described. We examined the reproducibility of the proteomic patterns across datasets in more detail. Our analysis reveals that the pattern that enabled successful classification is biologically implausible and that the method, properly applied, does not classify the data accurately. We show that the method used in previously published studies does not establish reproducibility and performs no better than chance for classifying the second dataset, in part because the second dataset is easy to classify correctly. We conclude that the reproducibility of the proteomic profiling approach has yet to be established.

Female↗
PubMed2005

Significant differences in nipple aspirate fluid protein expression between healthy women and those with breast cancer demonstrated by time-of-flight mass spectrometry.

New approaches are needed for the early detection of breast cancer. Proteomic profiling technologies, such as surface-enhanced laser desorption ionization mass spectrometry (SELDI-MS), may be able to identify tumor markers in biological fluids. The objective of this study was to determine whether there are differences in protein expression patterns in nipple aspirate fluid (NAF) from the cancerous and noncancerous breasts of patients with unilateral breast cancer and the breasts of healthy volunteers. Paired NAF samples were obtained from 23 women with stage I or II unilateral invasive breast carcinoma and five healthy female volunteers. Aliquots of the samples were applied to SELDI Protein-chip arrays (WCX2 and IMAC3-Cu++), and protein expression was analyzed using time-of-flight MS. A total of 463 distinct peaks were detected and analyzed. In breast cancer patients, no differences in protein expression were identified between the breast with the intact primary carcinoma and the contralateral noncancerous breast. Seventeen peaks were overexpressed in cancer-bearing breasts compared to breasts of healthy volunteers (p < 0.0005). When spectra from the nontumor-bearing breasts of breast cancer patients were compared with spectra from breasts of healthy volunteers, two peaks that were overexpressed in breast cancer patients and one peak that was underexpressed in breast cancer patients were detected (p < 0.0027). SELDI-MS was able to identify differences in the phenotypic proteomic profile of NAF samples obtained from patients with early-stage breast cancer and healthy women. Proteomic screening techniques such as SELDI-MS analysis of NAF may be useful for breast cancer screening and diagnosis.

Biopsy, Needle↗
PubMed2024

Proteomic serum profiles before and after lipoprotein apheresis in patients with peripheral artery disease with ulceration.

INTRODUCTION: The efficacy of lipoprotein apheresis (LA) in peripheral arterial disease (PAD) has been primarily attributed to its anti-atherosclerotic effects through the adsorption of lipoproteins. However, the other potential effects of LA remain unknown. We evaluated changes in serum profiles before and after LA using a comprehensive analysis to explore the underlying mechanism. METHODS: Ten patients with leg ulcers were included from the LETS-PAD study, in which patients with lipoprotein-controlled PAD underwent LA. Serum samples collected at baseline and 1&#x2009;month after LA were analyzed for proteomic changes. RESULTS: Six patients exhibited ulcer epithelialization and skin perfusion pressure improvement. Proteomic analysis identified 2033 proteins. Fifty-five proteins showed significant differences. B-cell lymphoma protein-2 associated X (BAX) and C-X-C motif chemokine 10 (CXCL10) were downregulated. CONCLUSION: Serum BAX and CXCL10 levels significantly decreased after LA, which may be involved in the ulcer epithelialization mechanism of LA, which potentially acts through angiogenesis promotion.

Humans↗
PubMed2000

Comprehensive analyses of prostate gene expression: convergence of expressed sequence tag databases, transcript profiling and proteomics.

Several methods have been developed for the comprehensive analysis of gene expression in complex biological systems. Generally these procedures assess either a portion of the cellular transcriptome or a portion of the cellular proteome. Each approach has distinct conceptual and methodological advantages and disadvantages. We have investigated the application of both methods to characterize the gene expression pathway mediated by androgens and the androgen receptor in prostate cancer cells. This pathway is of critical importance for the development and progression of prostate cancer. Of clinical importance, modulation of androgens remains the mainstay of treatment for patients with advanced disease. To facilitate global gene expression studies we have first sought to define the prostate transcriptome by assembling and annotating prostate-derived expressed sequence tags (ESTs). A total of 55000 prostate ESTs were assembled into a set of 15953 clusters putatively representing 15953 distinct transcripts. These clusters were used to construct cDNA microarrays suitable for examining the androgen-response pathway at the level of transcription. The expression of 20 genes was found to be induced by androgens. This cohort included known androgen-regulated genes such as prostate-specific antigen (PSA) and several novel complementary DNAs (cDNAs). Protein expression profiles of androgen-stimulated prostate cancer cells were generated by two-dimensional electrophoresis (2-DE). Mass spectrometric analysis of androgen-regulated proteins in these cells identified the metastasis-suppressor gene NDKA/nm23, a finding that may explain a marked reduction in metastatic potential when these cells express a functional androgen receptor pathway.

DNA, Complementary↗