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At least 19 recordsLinked to original sources
PubMed2025

A SlEIN2-centered epigenetic network equilibrates fruit ripening and innate immunity in tomato.

Ethylene and DNA/RNA methylation serve as essential factors in controlling fruit ripening. In tomato, the mRNA N6-methyladenosine (m6A) demethylase SlALKBH2 regulates mRNA stability of the DNA 5-methylcytosine demethylase gene SlDML2 via modulating m6A modifications. However, the interplay between ethylene and these epigenetic marks remains unclear. Here, we show that SlDML2 expression is significantly inhibited in slein2 fruits, but remains unchanged in the high-order sleil mutant (sleil1 sleil2 sleil3/SlEIL3 sleil4 and sleil1 sleil2/SlEIL2 sleil3 sleil4) fruits, indicative of post-transcriptional regulation of SlDML2 expression by SlEIN2, a core ethylene signaling component acting upstream of the master transcription factors SlEILs. Interestingly, SlEIN2 preferentially regulates the asymmetric CHH methylation in promoters of several key ripening regulator genes. Mechanistically, SlEIN2 physically interacts with SlALKBH2, which promotes SlDML2 expression in a SlEIN2-dependent manner. Furthermore, SlAGO4A and SlAGO4B, components of the RNA-directed DNA methylation pathway, were upregulated in slein2 fruits. Silencing SlAGO4A/B in wild-type fruit caused precocious ripening with necrosis, indicative of hyperimmunity. Conversely, SlAGO4A/B silencing in slein2 markedly delayed this hyperimmunity. Taken together, our study reveals that ethylene, beyond transcriptional regulation, employs an elaborate epigenetic machinery mediated by the SlAGO4A/B-SlEIN2-SlALKBH2 module to balance fruit ripening and innate immunity.

Solanum lycopersicum↗
PubMed2006

Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage.

Methylating agents are ubiquitous in the environment, and central in cancer therapy. The 1-methyladenine and 3-methylcytosine lesions in DNA/RNA contribute to the cytotoxicity of such agents. These lesions are directly reversed by ABH3 (hABH3) in humans and AlkB in Escherichia coli. Here, we report the structure of the hABH3 catalytic core in complex with iron and 2-oxoglutarate (2OG) at 1.5 A resolution and analyse key site-directed mutants. The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. This experimentally establishes hABH3 as a structural member of the Fe(II)/2OG-dependent dioxygenase superfamily, which couples substrate oxidation to conversion of 2OG into succinate and CO2. A positively charged DNA/RNA binding groove indicates a distinct nucleic acid binding conformation different from that predicted in the AlkB structure with three nucleotides. These results uncover previously unassigned key catalytic residues, identify a flexible hairpin involved in nucleotide flipping and ss/ds-DNA discrimination, and reveal self-hydroxylation of an active site leucine that may protect against uncoupled generation of dangerous oxygen radicals.

AlkB Homolog 1, Histone H2a Dioxygenase↗
PubMed1994

Folate and cancer: a review of the literature.

Folate, a water-soluble vitamin, part of the vitamin B complex, plays an important role in methylation reactions and DNA/RNA synthesis. This review examines the experimental and epidemiological evidence for the association between folate status and risk of cancer. Data have accumulated indicating that low folate status may promote carcinogenesis. Low folate levels are associated with cytogenetic abnormalities in vivo and in vitro. Findings from animal studies are conflicting and suggest that the effect of folate on neoplasia depends on factors such as the animal and tumor model, the type, timing, dose, and length of application of carcinogen, the stage of carcinogenesis, and the level and form of folate administered. Epidemiological studies examined the association between folate and cancer of the cervix, colorectum, lung, esophagus, and brain and suggest that low folate status may play an important role early in the neoplastic process. The potential for inhibition of precursor lesions in the cervix and colorectum, namely, cervical intraepithelial neoplasia and adenomatous polyps, respectively, is of particular interest. Additional research designed to clarify the role of folate in carcinogenesis is warranted.

Animals↗
PubMed1999

DNA aptamers selected against the HIV-1 trans-activation-responsive RNA element form RNA-DNA kissing complexes.

In vitro selection was performed in a DNA library, made of oligonucleotides with a 30-nucleotide random sequence, to identify ligands of the human immunodeficiency virus type-1 trans-activation-responsive (TAR) RNA element. Aptamers, extracted after 15 rounds of selection-amplification, either from a classical library of sequences or from virtual combinatorial libraries, displayed an imperfect stem-loop structure and presented a consensus motif 5'ACTCCCAT in the apical loop. The six central bases of the consensus were complementary to the TAR apical region, giving rise to the formation of RNA-DNA kissing complexes, without disrupting the secondary structure of TAR. The RNA-DNA kissing complex was a poor substrate for Escherichia coli RNase H, likely due to steric and conformational constraints of the DNA/RNA heteroduplex. 2'-O-Methyl derivatives of a selected aptamer were binders of lower efficiency than the parent aptamer in contrast to regular sense/antisense hybrids, indicating that the RNA/DNA loop-loop region adopted a non-canonical heteroduplex structure. These results, which allowed the identification of a new type of complex, DNA-RNA kissing complex, demonstrate the interest of in vitro selection for identifying non-antisense oligonucleotide ligands of RNA structures that are of potential value for artificially modulating gene expression.

Base Sequence↗
PubMed2005

Bioinformatic mapping of AlkB homology domains in viruses.

BACKGROUND: AlkB-like proteins are members of the 2-oxoglutarate- and Fe(II)-dependent oxygenase superfamily. In Escherichia coli the protein protects RNA and DNA against damage from methylating agents. 1-methyladenine and 3-methylcytosine are repaired by oxidative demethylation and direct reversal of the methylated base back to its unmethylated form. Genes for AlkB homologues are widespread in nature, and Eukaryotes often have several genes coding for AlkB-like proteins. Similar domains have also been observed in certain plant viruses. The function of the viral domain is unknown, but it has been suggested that it may be involved in protecting the virus against the post-transcriptional gene silencing (PTGS) system found in plants. We wanted to do a phylogenomic mapping of viral AlkB-like domains as a basis for analysing functional aspects of these domains, because this could have some relevance for understanding possible alternative roles of AlkB homologues e.g. in Eukaryotes. RESULTS: Profile-based searches of protein sequence libraries showed that AlkB-like domains are found in at least 22 different single-stranded RNA positive-strand plant viruses, but mainly in a subgroup of the Flexiviridae family. Sequence analysis indicated that the AlkB domains probably are functionally conserved, and that they most likely have been integrated relatively recently into several viral genomes at geographically distinct locations. This pattern seems to be more consistent with increased environmental pressure, e.g. from methylating pesticides, than with interaction with the PTGS system. CONCLUSIONS: The AlkB domain found in viral genomes is most likely a conventional DNA/RNA repair domain that protects the viral RNA genome against methylating compounds from the environment.

Adenine↗
PubMed1990

Physiochemical characterization of substituted chromeno[4,3-b][1,5]benzodiazepine stereoisomers designed as cell membrane active antitumor agents.

As an alternative to naturally occurring pyrrolo[2,1-c][1,4]benzodiazepines (e.g., antramycin) which possess properties of DNA alkylation, we have designed several antileukemic chromeno[4,3-b][1,5]benzodiazepine derivatives with potential activity toward leukemia cell membranes and the cyclic nucleotide system. The cis and trans diastereoisomers were characterized by NMR. The absolute configurations of the enantiomers were established by X-ray diffraction and circular dichroism (CD) measurements. By means of absorption spectroscopy and determinations of fluorescence and fluorescence decay, it was found that the cancerostatically active compound (+)(6aR, 13aS)-3,4-dimethoxy-10,11-dimethyl-6,6a,7,8,13, 13a-hexahydrochromeno[4,3-b][1,5]benzodiazepine (ZIMET 54/79) and its biologically inactive (-) enantiomer (ZIMET 55/79) interact with liposomal membranes. At pH values of 6.0 and 7.3 the long-wave absorption bands of these agents showed weak bathochromic and hypochromic effects upon addition of neutral, and positively and negatively charged phosphatidylcholine and phosphatidylcholine/cholesterol liposomes. Such spectral changes are interpreted as resulting from the binding of both agents to phospholipid bilayers. Steady-state determinations using the membrane probe 1-anilino-8-naphthalenesulfonic acid (1,8-ANS) led to the observation of a small decrease in fluorescence intensity in the presence of either agent. Time-resolved measurements demonstrate that the mechanism of action of the agents occurs mainly through the partial displacement of probe molecules from regions of hydrophobic binding to areas of greater solvent accessibility. No significant differences in binding between the cancerostatically active and inactive enantiomers with liposomes (archiral systems) were detectable on the basis of spectrophotometric and fluorescence determinations. Cell membrane bound adenylate cyclase is stimulated by ZIMET 54/79, resulting in an increase of 103% in the level of cAMP in mouse L1210 leukemia cells. On examination of structure-activity relationships, it was found that the biological activity (leukemia L1210, P388, Lewis lung carcinoma, melanoma B16, increase in cAMP) is correlated with the particular configuration (6aR,13aS) and type of substituent at positions 3 and 4 of the benzo ring in the case of alkoxy groups and positions 10 and 11 for methyl groups. No activity was detected toward DNA/RNA using microbial test systems.

Animals↗
PubMed2005

A lipidomic study of the effects of N-methyl-N'-nitro-N-nitrosoguanidine on sphingomyelin metabolism.

Systems biology is a new and rapidly developing research area in which, by quantitatively describing the interaction among all the individual components of a cell, a systems-level understanding of a biological response can be achieved. Therefore, it requires high-throughput measurement technologies for biological molecules, such as genomic and proteomic approaches for DNA/RNA and protein, respectively. Recently, a new concept, lipidomics, which utilizes the mass spectrometry (MS) method for lipid analysis, has been proposed. Using this lipidomic approach, the effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on sphingomyelin metabolism, a major class of sphingolipids, were evaluated. Sphingomyelin molecules were extracted from cells and analyzed by matrix-assisted laser desorption ionization-time of flight MS. It was found that MNNG induced profound changes in sphingomyelin metabolism, including the appearance of some new sphingomyelin species and the disappearance of some others, and the concentrations of several sphingomyelin species also changed. This was accompanied by the redistribution of acid sphingomyelinase (ASM), a key player in sphingomyelin metabolism. On the other hand, imipramine, an inhibitor of ASM, caused the accumulation of sphingomyelin. It also prevented some of the effects of MNNG, as well as the redistribution of ASM. Taken together, these data suggested that the lipidomic approach is highly effective for the systematic analysis of cellular lipids metabolism.

Amnion↗
PubMed1989

Early events in methyl methanesulfonate enhancement of adenovirus transformation of cloned rat embryo fibroblast cells.

Pretreatment of a cloned rat embryo fibroblast (CREF) cell line with methyl methanesulfonate (MMS) prior to infection with a specific host-range and cold-sensitive type 5 adenovirus mutant (H5hr1), results in a unique carcinogen enhancement of transformation (CET) phenotype (Carcinogenesis 8:967, 1987). By using low-density clonal assays and in situ hybridization techniques with 32P-labeled type 5 adenovirus (Ad5) probes, we demonstrated that 5-10 d following infection the proportion of CREF colonies containing H5hr1 DNA and RNA is increased two- to threefold as a result of pretreatment with MMS. Twenty-five days following infection of CREF cells, Ad5 DNA assays showed that both solvent and MMS-pretreated CREF colonies no longer contained detectable levels of viral DNA or RNA. Analysis of free viral DNA by the Hirt procedure suggested that more free viral DNA persisted in MMS-pretreated H5hr1-infected CREF cells than in solvent-pretreated H5hr1-infected CREF cells. The relative amount of free viral DNA in both types of cultures was directly related to the multiplicity of H5hr1 infection and decreased with time following infection. As observed using in situ hybridization techniques, by 25 d after infection no free viral DNA was detected in either MMS- or solvent-pretreated H5hr1-infected CREF cells. By using a protein synthesis inhibitor (cycloheximide) and an RNA transcription inhibitor (actinomycin D), it was further demonstrated that the ability of MMS to induce a unique CET in CREF cells following infection with H5hr1 was dependent on the synthesis of new protein and RNA. In contrast, inhibition of protein and RNA synthesis did not alter the de novo rate of H5hr1 transformation of CREF cells. Temporal kinetic studies indicated that the ability of MMS to enhance H5hr1 transformation of CREF cells and to increase the percentage of CREF colonies containing Ad5 genetic information is regulated in a strict temporal manner. The results of the present investigation suggest that the ability of MMS to enhance H5hr1 transformation of CREF cells is dependent on the induction of new protein(s) in CREF cells, and enhancement is associated with an increase in the proportion of cells in the infected CREF cell population that initially contain Ad5 DNA/RNA.

Adenoviruses, Human↗
PubMed2006

Pharmacogenomics of the polyamine analog 3,8,13,18-tetraaza-10,11-[(E)-1,2-cyclopropyl]eicosane tetrahydrochloride, CGC-11093, in the colon adenocarcinoma cell line HCT1161.

Polyamine analogs are known to inhibit tumorigenesis at least in part by mimicking some of the regulatory roles of natural polyamines. To begin the identification of those signaling pathways that are involved in differential cellular responses to the synthetic conformationally restricted polyamine analog CGC-11093, we conducted gene expression profiling, proteomic, and genome-wide DNA methylation and histone acetylation analyses of the HCT116 colon adenocarcinoma cell line after treatment with this analog. Gene expression analysis was performed using Affymetrix GeneChip human genome U133 Plus 2.0 arrays. Changes in protein expression were evaluated using 2D polyacrylamide gels followed by LCMS/MS. DNA methylation was measured using 6,800 element CpG island microarrays. Treatment of cells with CGC-11093 at concentrations ranging from 0.1 to 10 microM caused inhibition of cell growth and metabolic activity, but only minimally affected cell viability. Gene expression analysis showed concentration-dependent effects of CGC-11093 on the DNA/RNA binding transcription factor, cell cycle, signaling, transport, cytoskeletal/structural, and serine protease genes. Functional gene analysis revealed distinct expression patterns related to inhibition of cell cycle control, TGF beta signaling, proteasome and RNA polymerase pathways, upregulation of the aminoacyl-tRNA synthesis pathway, and perturbations in the MAPK and Wnt signaling pathways. Microarray results were validated for selected genes with real time RT PCR. Proteomics analysis showed correlative changes in the expression of proteins involved in the regulation of proteasome function (proteasome subunit Y) and tRNA synthesis. CGC-11093 treatment did not produce any detectable changes in DNA methylation or histone acetylation in cells. This study validates specific target pathways for a specific conformationally restricted polyamine analog and suggests the utility of combined gene and DNA methylation microarrays along with proteomic analyses as a useful approach to the evaluation of the mechanisms of action of anticancer drugs.

Acetylation↗
PubMed1991

Synthesis and antiviral and cytostatic properties of 3'-deoxy-3'-fluoro- and 2'-azido-3'-fluoro-2',3'-dideoxy-D-ribofuranosides of natural heterocyclic bases.

A series of 3'-deoxy-3'-fluoro- and 2'-azido-2',3'-dideoxy-3'-fluoro-D-ribofuranosides of natural heterocyclic bases have been synthesized with the use of universal carbohydrate precursors, viz., 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-D-ribofuranose and methyl 2-azido-5-O-benzoyl-2,3-dideoxy-3-fluoro-beta-D-ribofuranoside, respectively. The cytostatic and antiviral activity of the compounds was evaluated against a variety of tumor cell lines and DNA/RNA viruses, respectively. As the most active compound, from both a cytostatic and antiviral activity viewpoint, emerged 3'-deoxy-3'-fluoroadenosine. It inhibited the proliferation of some tumor cell lines (i.e. murine leukemia L1210 and human T-lymphocyte MT-4) at a concentration of 0.2-2 micrograms/mL, and proved inhibitory to the replication of positive-stranded RNA viruses (i.e. polio, Coxsackie, Sindbis, Semliki forest), double-stranded RNA viruses (i.e. reo), and some DNA viruses (i.e. vaccinia) at a concentration of 1-4 micrograms/mL, which is well below the cytotoxicity threshold (40 micrograms/mL).

Animals↗
PubMed2006

Polyelectrolyte functionalized magnetic emulsion for specific isolation of nucleic acids.

A magnetic oil in water (o/w) emulsion was cationized by adsorption of poly(ethyleneimine) (PEI). In a subsequent step, the cationic particles were derivatized with partially hydrolyzed poly(maleic anhydride-alt-methyl vinyl ether) copolymer (PMAMVE) to lead negatively charged colloids. The experimental conditions for the covalent grafting of the PMAMVE were selected on the basis of colloidal stability, charge inversion and absence of inhibition of the enzymatic DNA/RNA amplification reactions. Once the experimental conditions were selected, oligonucleotides (ODN) bearing particles were obtained according to the sequential process: (i) grafting of single stranded ODNs onto PMAMVE; (ii) grafting of the PMAMVE-ODN conjugates onto the cationic particles according to the conditions defined above. In this strategy, both steps could be independently controlled. The ODN-PMAMVE-particles conjugates were very stable with time, did not inhibit RT-PCR and were capable of hybridizing specifically with the complementary target.

Emulsions↗
PubMedDate not supplied

Predicted roles for hypothetical proteins in the low-temperature expressed proteome of the Antarctic archaeon Methanococcoides burtonii.

Using liquid chromatography-mass spectrometry, 528 proteins were identified that are expressed during growth at 4 degrees C in the cold adapted archaeon, Methanococcoides burtonii. Of those, 135 were annotated previously as unique or conserved hypothetical proteins. We have performed a comprehensive, integrated analysis of the latter proteins using threading, InterProScan, predicted subcellular localization and visualization of conserved gene context across multiple prokaryotic genomes. Functional information was obtained for 55 proteins, providing new insight into the physiology of M. burtonii. Many of the proteins were predicted to be involved in DNA/RNA binding or modification and cell signaling, suggesting a complex, uncharacterized regulatory network controlling cellular processes during growth at low-temperature. Novel enzymatic functions were predicted for several proteins, including a putative candidate gene for the posttranslational modification of the key methanogenesis enzyme coenzyme M methyl reductase. A bacterial-like CRISPR locus was identified as a strong candidate for archaeal-bacterial lateral gene transfer. Gene context analysis proved a valuable augmentation to the other predictive methods in several cases, by revealing conserved gene associations and annotations in other microbial genomes. Our results underscore the importance of addressing the "hypothetical protein problem" for a complete understanding of cell physiology.

Adaptation, Physiological↗
PubMed2004

Aberrant activity of the DNA repair enzyme AlkB.

Escherichia coli AlkB is a DNA/RNA repair enzyme containing a mononuclear Fe(II) site that couples the oxidative decomposition of alpha-ketoglutarate (alphaKG) to the hydroxylation of 1-methyladenine or 3-methylcytosine lesions in DNA or RNA, resulting in release of formaldehyde and restoration of the normal bases. In the presence of Fe(II), alphaKG, and oxygen, but the absence of methylated DNA, AlkB was found to catalyze an aberrant reaction that generates a blue chromophore. The color is proposed to derive from Fe(III) coordinated by a hydroxytryptophan at position 178 as revealed by mass spectrometric analysis. Protein structural modeling confirms that Trp 178 is reasonably positioned to react with the Fe(IV)-oxo intermediate proposed to form at the active site.

5-Hydroxytryptophan↗
PubMed1992

Photochemically obtained N-demethyl derivatives of anthracyclines.

New N-monodemethyl and N-didemethyl derivatives were obtained from seven N-dimethylamino sugar (rhodosamine)-containing anthracyclines by photochemical reaction and their in vitro bioactivities against L1210 cell culture were compared with those of their N-dimethyl parent compounds. N-Demethyl derivatives obtained from betaclamycin T (7-O-rhodosaminyl-beta-rhodomycinone) were much more cytotoxic while those from the other six antibiotics were rather less active as compared with their parent compounds. The N-demethylation also gave a considerably greater decrease in the inhibitory activity on RNA synthesis as compared to DNA synthesis, so that the N-demethyl derivatives showed smaller IC50 ratios on DNA/RNA than their parent compounds.

Animals↗
PubMed2004

Substrate specificities of bacterial and human AlkB proteins.

Methylating agents introduce cytotoxic 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) residues into nucleic acids, and it was recently demonstrated that the Escherichia coli AlkB protein and two human homologues, hABH2 and hABH3, can remove these lesions from DNA by oxidative demethylation. Moreover, AlkB and hABH3 were also found to remove 1-meA and 3-meC from RNA, suggesting that cellular RNA repair can occur. We have here studied the preference of AlkB, hABH2 and hABH3 for single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA), and show that AlkB and hABH3 prefer ssDNA, while hABH2 prefers dsDNA. This was consistently observed with three different oligonucleotide substrates, implying that the specificity for single-stranded versus double-stranded DNA is sequence independent. The dsDNA preference of hABH2 was observed only in the presence of magnesium. The activity of the enzymes on single-stranded RNA (ssRNA), double-stranded RNA (dsRNA) and DNA/RNA hybrids was also investigated, and the results generally confirm the notion that while AlkB and hABH3 tend to prefer single-stranded nucleic acids, hABH2 is more active on double-stranded substrates. These results may contribute to identifying the main substrates of bacterial and human AlkB proteins in vivo.

AlkB Homolog 1, Histone H2a Dioxygenase↗
PubMed1992

Minimum ribonucleotide requirement for catalysis by the RNA hammerhead domain.

Several mixed DNA/RNA and 2'-O-methylribonucleotide/RNA analogues derived from the "hammerhead" domain of RNA catalysis have been prepared to study the minimum ribonucleotide requirement for catalytic activity. Oligodeoxyribonucleotides containing from seven to as few as four ribonucleotides are active in cleaving a substrate RNA. Predominantly deoxyribonucleotide-containing analogues have kcat values 20-300 and kcat/KM values approximately 100-2000 times lower than those of all-RNA ribozyme. In the case of predominantly 2'-O-methyl analogues, at least five ribonucleotides are needed to assure catalytic activity. In addition, both predominantly deoxyribonucleotide and 2'-O-methyl oligomers are at least 3 orders of magnitude more stable than an all-RNA ribozyme in incubations with RNase A and a yeast extract. These results suggest that the ribophosphate backbone is not a strict requirement for ribozyme-type catalysis. The identification of the four required ribonucleotides in the hammerhead catalytic domain provides valuable information for the rational design of chemical species having ribonuclease activities.

Base Sequence↗
PubMed2005

Synthesis of antisense oligonucleotides containing a photocleavable protecting group on a guanine base and their photoinduced duplex formation.

An oligonucleotide containing a photocleavable protecting group at a guanine base was synthesized to induce the duplex formation by photo-irradiation. Alpha-methyl-2-nitropiperonyl (MeNP) group was used for the photocleavable protecting group at O6 position of deoxyguanosine. The oligonucleotide containing MeNP group (MeNP-ODN:5'-dTTCTG(MeNP)TCTGT-3') was synthesized by phosphoramidite method. The MeNP group was found to be removable by UV irradiation at wavelength of 365 nm for 5 min in 98% yield. UV-melting temperature (Tm value) analysis indicated that the duplex of MeNP-ODN with the complementary RNA was significantly unstable compared with the unmodified DNA/RNA duplex (deltaTm = -25 degrees C). After UV irradiation at 365 nm, the Tm value of the mixture increased to the same as that of the unmodified duplex. These results suggest that the RNA binding ability of the MeNP-ODN can be induced by photocleavage of the MeNP group.

Benzodioxoles↗
PubMed2004

Circulating nucleic acids and proteomics of plasma/serum: clinical utility.

Circulating tumor-specific nucleic acids have been identified in plasma, serum, and other body fluids from cancer patients with tumors originating in almost any organ site. Polymerase chain reaction provides a highly sensitive and specific technique for the detection of these genetic changes in a limited amount of tissue/fluid. The presence of elevated levels of free DNA/RNA in many medical conditions, malignancy, and infectious processes is being investigated for screening, diagnosis, prognosis, surveillance for occult disease progression, identifying potential therapeutic targets, and monitoring treatment response. Additionally, elevated fetal DNA/RNA in maternal blood is being used to determine gender identity, assess chromosomal abnormalities, and monitor pregnancy-associated complications. Questions remain on the etiology, characteristics, stability, and potential pathologic consequences of cell-free DNA/RNA in the circulation. Nevertheless, nucleic acid-based assays that monitor plasma, serum, and body fluids provide a noninvasive, facile, and practical method for assessing patients. Proteomic profiling may prove complementary to a total functionality approach in providing a comprehensive evaluation of the patient's disease.

Biomarkers, Tumor↗