Kegg Pathway: Biotin metabolism

Arch Ophthalmol. 2009 Nov; 127(11): 1475-80
Yang L, Kim JH, Kovacs KD, Arroyo JG, Chen DF

OBJECTIVE: To determine whether systemic minocycline can protect photoreceptors in experimental retinal detachment (RD). METHODS: Retinal detachment was induced in mice by subretinal injection of sodium hyaluronate, 1.4%. In 1 experiment, mice received daily injections of minocycline (group 1) or saline (group 2). In a second experiment, mice were treated with minocycline or saline beginning 24 hours prior, immediately after, or 24 hours after experimental RD. In both experiments, photoreceptor cell survival and apoptosis were assessed by immunohistochemistry with primary antibodies against photoreceptor cell markers, rod rhodopsin, and cone opsin, and by terminal deoxynucleotidyl transferase-mediated dUTP-Biotin end labeling. RESULTS: Photoreceptor cell apoptosis was detected at day 1 after experimental RD, with apoptotic cells peaking in number at day 3 and dropping by day 7. Treatment with minocycline significantly reduced the number of apoptotic photoreceptor cells associated with RD when given 24 hours before or even 24 hours after RD. CONCLUSIONS: Our data suggest that minocycline may be useful in the treatment of photoreceptor degeneration associated with RD, even when given up to 24 hours after RD. CLINICAL RELEVANCE: Use of minocycline in patients with macula-off RD may prevent photoreceptor apoptosis and glial cell proliferation, improving final visual outcomes.

Biochem Biophys Res Commun. 2009 Nov 11;
Cho YS, Lee JI, Shin D, Kim HT, Jung HY, Lee TG, Kang LW, Ahn YJ, Cho HS, Heo YS

Acetyl-CoA carboxylases (ACCs) have been highlighted as therapeutic targets for obesity and diabetes, as they play crucial roles in fatty acid metabolism. ACC activity is regulated through the short-term mechanism of inactivation by reversible phosphorylation. Here, we report the crystal structures of the Biotin carboxylase (BC) domain of human ACC2 phosphorylated by AMP-activated protein kinase (AMPK). The phosphorylated Ser222 binds to the putative dimer interface of BC, disrupting polymerization and providing the molecular mechanism of inactivation by AMPK. We also determined the structure of the human BC domain in complex with soraphen A, a macrocyclic polyketide natural product. This structure shows that the compound binds to the binding site of phosphorylated Ser222, implying that its inhibition mechanism is the same as that of phosphorylation by AMPK.

J Am Chem Soc. 2009 Nov 18; 131(45): 16430-8
Puthenveetil S, Liu DS, White KA, Thompson S, Ting AY

Escherichia coli lipoic acid ligase (LplA) catalyzes ATP-dependent covalent ligation of lipoic acid onto specific lysine side chains of three acceptor proteins involved in oxidative metabolism. Our lab has shown that LplA and engineered mutants can ligate useful small-molecule probes such as alkyl azides ( Nat. Biotechnol. 2007 , 25 , 1483 - 1487 ) and photo-cross-linkers ( Angew. Chem., Int. Ed. 2008 , 47 , 7018 - 7021 ) in place of lipoic acid, facilitating imaging and proteomic studies. Both to further our understanding of lipoic acid metabolism, and to improve LplA's utility as a biotechnological platform, we have engineered a novel 13-amino acid peptide substrate for LplA. LplA's natural protein substrates have a conserved beta-hairpin structure, a conformation that is difficult to recapitulate in a peptide, and thus we performed in vitro evolution to engineer the LplA peptide substrate, called "LplA Acceptor Peptide" (LAP). A approximately 10(7) library of LAP variants was displayed on the surface of yeast cells, labeled by LplA with either lipoic acid or bromoalkanoic acid, and the most efficiently labeled LAP clones were isolated by fluorescence activated cell sorting. Four rounds of evolution followed by additional rational mutagenesis produced a "LAP2" sequence with a k(cat)/K(m) of 0.99 muM(-1) min(-1), >70-fold better than our previous rationally designed 22-amino acid LAP1 sequence (Nat. Biotechnol. 2007, 25, 1483-1487), and only 8-fold worse than the k(cat)/K(m) values of natural lipoate and Biotin acceptor proteins. The kinetic improvement over LAP1 allowed us to rapidly label cell surface peptide-fused receptors with quantum dots.

Ren Fail. 2009; 31(7): 562-6
Kuloglu T, Dabak DO

BACKGROUNDS/AIMS: Ghrelin, a recently discovered hormone, is released largely from stomach and might affect insulin secretion and glucose metabolism. The aim of this study was to determine the immunohistochemical localization of ghrelin in streptozotocin-induced diabetic rat kidneys. METHODS: Fifty-four adult male Wistar rats were used in this study. All rats were divided into nine groups according to three time points of the study (2, 4, and 6 weeks) as control group, control group given 0.1 M phosphate-citrate, and diabetic group given 50 mg/kg streptozotocin intraperitoneally. The rats in all groups were decapitated at the end of 2, 4, and 6 weeks of the study. The kidneys of the rats were removed, and tissue samples were processed by using routine paraffin techniques. The samples were immunohistochemically stained using avidin-Biotin-peroxidase method for ghrelin immunoreactivity. RESULTS: There were no differences of ghrelin immunoreactivity between the control groups. Ghrelin immunoreactivity was observed in both distal tubulus and collecting ducts in the diabetic groups, while it was detected only in distal tubules of the control groups. The intensity of ghrelin immunoreactivity was increased at 4 and 6 weeks of the study in the diabetic groups. CONCLUSION: Increased ghrelin immunoreactivity in the diabetic rat kidney tissues suggests that ghrelin may contribute to the pathophysiological mechanism of diabetic nephropathy.

Biochemistry. 2009 Nov 17; 48(45): 10782-92
Reyda MR, Fugate CJ, Jarrett JT

Biotin synthase (BioB) is an iron-sulfur enzyme that catalyzes the last step in Biotin biosynthesis, the insertion of sulfur between the C6 and C9 atoms of dethioBiotin to complete the thiophane ring of Biotin. Recent in vitro experiments suggest that the sulfur is derived from a [2Fe-2S](2+) cluster within BioB, and that the remnants of this cluster dissociate from the enzyme following each turnover. For BioB to catalyze multiple rounds of Biotin synthesis, the [2Fe-2S](2+) cluster in BioB must be reassembled, a process that could be conducted in vivo by the ISC or SUF iron-sulfur cluster assembly systems. The bacterial ISC system includes HscA, an Hsp70 class molecular chaperone, whose yeast homologue has been shown to play an important but nonessential role in assembly of mitochondrial FeS clusters in Saccharomyces cerevisiae. In this work, we show that in Escherichia coli, HscA significantly improves the efficiency of the in vivo assembly of the [2Fe-2S](2+) cluster on BioB under conditions of low to moderate iron. In vitro, we show that HscA binds with increased affinity to BioB missing one or both FeS clusters, with a maximum of two HscA molecules per BioB dimer. BioB binds to HscA in an ATP/ADP-independent manner, and a high-affinity complex is also formed with a truncated form of HscA that lacks the nucleotide binding domain. Further, the BioB-HscA complex binds the FeS cluster scaffold protein IscU in a noncompetitive manner, generating a complex that contains all three proteins. We propose that HscA plays a role in facilitating the transfer of FeS clusters from IscU into the appropriate target apoproteins such as Biotin synthase, perhaps by enhancing or prolonging the requisite protein-protein interaction.

Zhongguo Gu Shang. 2009 Sep; 22(9): 692-3
Ma LJ, Zhang JJ, Wu HT

OBJECTIVE: To investigate the effect of high dose methylprednisolone (MP) on cell apoptosis and Bcl-2 expression after acute spinal cord injury (ASCI). METHODS: The 48 female rats were randomly divided into two groups:control group and experimental group. The spinal cord of rats were wounded at the level of T9,10 in moderate degree for each group. Thirty minutes after ASCI, the subjects in experimental group received MP injection through intraperitoneal with dosage of 30 mg/kg. Then a dosage of 5.4 mg/kg of MP was given through intraperitoneal injection every hour in 24 hours. The subjects in the control group received Normal Saline instead of MP with the same method. The impaired spinal cords were harvested on 4 h, 8 h, 1 d, 3 d, 7 d and 14 d after injury,and at each time point 4 rats were sacrificed in each group. The terminal deoxynucleotidal transferase-mediated DUTP-Biotin nick end labeling (TUNEL) and immunohistochemical measurement were used to observe neural apoptosis and Bcl-2 expression. RESULTS: Apoptosis cells were noted primarily at 4 h after injury, with a maximum presence in lesion center at 8 h. The apoptotic index of MP-treated group had distinctly less than that of control group in 8 h, 1 d and 3 d after trauma. The Bcl-2 increased in the experimental group. CONCLUSION: The administration of the high dose methylprednisolone (MP) can inhibite the apoptosis after acute spinal cord injury in rats and increase the expression of Bcl-2.

J Nutr. 2009 Oct 7;
Ho E, Zempleni J

The American Society for Nutrition hosted a symposium entitled Nutrients and Epigenetic Regulation of Gene Expression at the Experimental Biology meeting on April 20, 2009, in New Orleans, LA. The symposium was cochaired by Emily Ho from Oregon State University and the Linus Pauling Institute, and Janos Zempleni from the University of Nebraska at Lincoln. The goal of this symposium was to highlight the interactions among nutrients, epigenetics, and disease susceptibility. The symposium featured 4 speakers, each presenting novel insights into mechanisms by which nutrients participate in gene regulation. Janos Zempleni elucidated mechanisms by which the covalent binding of Biotin to histones represses transposable elements, thereby enhancing genome stability. Emily Ho shared valuable insights into bioactive food compounds that inhibit histone deacetylases. James Kirkland from the University of Guelph in Canada talked about a niacin-dependent poly(ADP-ribosylation) of histones, an epigenetic mark that is not currently being given full consideration in nutrition. Patrick Stover from Cornell University described the interrelationships among 1-carbon metabolism, DNA methylation, gene silencing, and their influence in the etiology of folate-related pathologies. All 4 presentations were videotaped and can be viewed online (www.nutrition.org).

J Chem Inf Model. 2009 Aug; 49(8): 1944-51
Fukunishi Y, Mitomo D, Nakamura H

We developed a new molecular dynamics simulation method for protein-ligand binding free energy calculation in an explicit water model. This method consists of three steps: (1) generation of a compound dissociation path starting from a stable protein-compound complex structure, (2) calculation of the free energy surface along the dissociation path, and (3) calculation of the free energy surface of a small area around the protein-compound complex structure, which is a free energy minimum. The protein-compound binding free energy is estimated from the information obtained by the above three steps. This method was applied to a small system, a 18-crown-6 ether with its ligand ion, and a realistic system consisting of a target protein with its inhibitor. This approximation worked well; the protein-inhibitor dissociation was successfully performed, and the binding free energies were calculated.

Pak J Biol Sci. 2009 May 15; 12(10): 750-7
Sohrabi M, Kalati FA, Vatansever S, Abbasi MM, Roshangar L, Khaki AA, Tuglu IM, Aydemir I, Dustar Y, Javadzadeh BY, Rad JS

The aim of the study is to determine the effect of Celecoxib administration, dietary or topical, on expression of Ki-67, c-erb-B2, bcl-2 and bax genes in rat tongue by the immunohistochemistry methods and also tdt-mediated dupt-Biotin nick end labeling assay in order to explore their role in malignant transformation and the proliferation rate, apoptosis rate in tongue squamous cell carcinoma. Effects of celecoxib on tongue carcinogenesis were investigated in 40 adult male Sprague Dawley 3-3.5 months rats initiated with 30 ppm 4-nitroquinoline-1-oxide. The immunohistochemical expression of Ki-67, bcl2, bax and c-erb-B2 were also examined for analysis of the effects of Celecoxib on tongue carcinogenesis. Differences among groups were statistically analyzed with one-way analysis of variance (SPSS-13, p < 0.05). At week 8, the incidence of tongue precancer lesions was reduced by Celecoxib and there were significant differences in the average expression of Ki-67 (p = 0.00), c-erb-B2 (p = 0.01), bax (p = 0.02), bcl2 (p = 0.02) and also in TUNEL assay (p = 0.00). The results suggest probably that the level of c-erb-B2, bcl-2 and bax expression could show behavior of squamous cell carcinoma in initiation phase of developing carcinoma.

Proc Natl Acad Sci U S A. 2009 Sep 15; 106(37): 15599-603
Wu C, Mino K, Akimoto H, Kawabata M, Nakamura K, Ozaki M, Ohmiya Y

We aimed to develop a far-red luminescence imaging technology for visualization of disease specific antigens on cell surfaces in a living body. First, we conjugated a far-red fluorescent indocyanine derivative to Biotinylated Cypridina luciferase. This conjugate produced a bimodal spectrum that has long-wavelength bioluminescence emission in the far-red region as a result of bioluminescence resonance energy transfer. To generate a far-red luminescent probe with targeting and imaging capabilities of tumors, we then linked this conjugate to an anti-human Dlk-1 monoclonal antibody via the Biotin-avidin interaction. This far-red luminescent probe enabled us to obtain high-resolution microscopic images of live, Dlk-1-expressing Huh-7 cells without an external light source, and to monitor the accumulation of this probe in tumor-bearing mice. Thus this far-red luminescent probe is a convenient analytical tool for the evaluations of monoclonal antibody localization in a living body.

Proc Natl Acad Sci U S A. 2009 Oct 13; 106(41): 17395-400
Tran JH, Chen CJ, Emr S, Schekman R

Genetic studies have identified a number of proteins required for the internalization of biosynthetic and endocytic cargo proteins transported to the multivesicular body (MVB). We have developed a cell-free reaction that recapitulates the internalization of a yeast biosynthetic membrane cargo protein, carboxypeptidase S (CPS), into the interior of an endosome. A recombinant form of CPS containing a Biotinylation site from an Escherichia coli protein is accumulated in a vps27 yeast mutant blocked in the MVB internalization event. Endosomes isolated from the vps27 mutant are exposed to E. coli Biotin ligase, which acts on only those CPS molecules with a cytosol-exposed N-terminal domain. Internalization of Biotin-tagged CPS is measured by the detection of trypsin-inaccessible, membrane-protected species. Biotinylated CPS internalization requires ATP and functional forms of Vps27p and Vps4p and depends on the availability of an exposed lysine residue critical for CPS ubiquitylation.

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2009 Feb; 23(1): 65-7
Zhan SB, Zhong JM, Mai ZP, Ye SQ, Zhou L, Zeng Y, Liao J

OBJECTIVE: To improve the existing serological early diagnosis method of nasopharyngeal carcinoma by improve the detection sensitivity. METHODS: The samples of 294 serum specimen from the prevention and treatment of nasopharyngeal cancer model base, involving 106 serum specimen from the patients suffering from nasopharyngeal cancer and 188 from the healthy testers. IgA/VCA antibody and IgA/EA antibody of the serums are tested by Streptavidin-Biotin-antibody immunoenzymatic test and normal traditional enzyme methods, SPSS statistical software is used to analyse the test results with chi2 test and t test. RESULTS: Referring to 106 patients, the sera antibody positive rate tested by Streptavidin-Biotin-antibody immunoenzymatic test method is obviously higher than that tested by traditional method; and the t test result of the GMT has significant difference in the two method. CONCLUSION: The modified method can improve the sensitivity of serology testing, ensure the specificity of test results, at the same time, improve the detection rate of nasopharyngeal carcinoma, so it can be applied to the early screen work of nasopharyngeal carcinoma.

Life Sci. 2009 Nov 4; 85(19-20): 685-92
Wang FS, Ko JY, Weng LH, Yeh DW, Ke HJ, Wu SL

AIMS: Long-term glucocorticoid administration is known to induce bone deterioration. Glycogen synthase kinase-3beta (GSK-3beta) signaling reportedly participates in bone remodeling. This study investigated whether GSK-3beta inhibitor could regulate glucocorticoid-induced inhibition of osteoblast differentiation in vitro or bone mass in vivo. MAIN METHODS: MC3T3-E1 osteoblasts were treated with kinase-inactive GSK-3beta mutant and 6-bromoindirubin-3'-oxim (BIO) and then exposed to 1microM dexamethasone. Survival and osteoblast differentiation of cell cultures were assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-Biotin nick end-labeling, quantitative RT-PCR, and von Kossa staining. Mineral density, biomechanical properties and microenvironments of BIO- and glucocorticoid-treated rat bone tissues were analyzed using dual-energy X-ray absorptiometry, material testing, and histomorphometry, respectively. KEY FINDINGS: Glucocorticoid decreased levels of phosphorylated Ser9-GSK-3beta and beta-catenin in osteoblast cultures. Kinase-inactive GSK-3beta mutant and BIO treatments attenuated dexamethasone-induced inhibition of beta-catenin, Runx2 abundance, and osteoblast differentiation but suppressed glucocorticoid-induced apoptosis of cell cultures. Exogenous BIO treatment alleviated methylprednisolone-induced impairment of mineral density, biomechanical strength, trabecular bone volume, osteoblast surface, and bone formation rate of rat bone tissue. BIO treatment also attenuated glucocorticoid-induced promotion of osteoclast surface and marrow adipocyte volume in bone tissue. Bone cells adjacent to glucocorticoid-stressed bone tissue displayed strong phosphorylated Ser9-GSK-3beta and beta-catenin immunostaining following BIO treatment. SIGNIFICANCE: Inhibition of GSK-3beta abrogated glucocorticoid-induced bone loss by increasing beta-catenin- and Runx2-mediated osteoblast differentiation. Controlling GSK-3beta signaling in bone cells may be a strategy for preventing glucocorticoid-induced osteopenia.

J Mol Biol. 2009 Nov 27; 394(2): 219-25
Zhou Y, Nie Y, Kaback HR

X-ray crystal structures of LacY (lactose permease of Escherichia coli) exhibit a large cytoplasmic cavity containing the residues involved in sugar binding and H(+) translocation at the apex and a tightly packed side facing the periplasm. However, biochemical and biophysical evidence provide a strong indication that a hydrophilic pathway opens on the external surface of LacY with closing of the cytoplasmic side upon sugar binding. Thus, an alternating-access mechanism in which sugar- and H(+)-binding sites at the approximate middle of the molecule are alternatively exposed to either side of the membrane is likely to underlie LacY-catalyzed sugar/H(+) symport. To further investigate periplasmic opening, we replaced paired residues on the tightly packed periplasmic side of LacY with Cys, and the effect of cross-linking was studied by testing the accessibility/reactivity of Cys148 with the elongated ( approximately 29 A), impermeant hydrophilic reagent maleimide-PEG2-Biotin. When the paired-Cys mutant Ile40-->Cys/Asn245-->Cys containing native Cys148 is oxidized to form a disulfide bond, the reactivity of Cys148 is markedly inhibited. Moreover, the reactivity of Cys148 in this mutant increases with the length of the cross-linking agent. In contrast, maleimide-PEG2-Biotin reactivity of Cys148 is unaffected by oxidation of two other paired-Cys mutants at the mouth of the periplasmic cavity. The data indicate that residues Ile40 and Asn245 play a primary role in gating the periplasmic cavity and provide further support for the alternating-access model.

J Microbiol. 2009 Aug; 47(4): 473-8
Demirev AV, Lee JS, Sedai BR, Ivanov IG, Nam DH

The gene locus for acetyl-CoA carboxylase (ACC) involved in the primary metabolism was identified from the genomic library of Streptomyces toxytricini which produces a lipase inhibitor lipstatin. The 7.4 kb cloned gene was comprised of 5 ORFs including accD1, accA1, hmgL, fadST1, and stsF. In order to confirm the biochemical characteristics of AccA1, the gene was overexpressed in Escherichia coli cells, and the recombinant protein was purified through Ni2+ affinity chromatography. Because most of the expressed AccAl was Biotinylated by host E. coli BirA in the presence of D-Biotin, the non-Biotinylated apo-AccA1 was purified after gene induction without D-Biotin, followed by exclusion of holo-AccA1 using streptavidin beads. The separated apo-AccA1 was post-translationally Biotinylated by S. toxytricini Biotin apo-protein ligase (BPL) in a time- and enzyme-dependent manner. This result supports that this gene cluster of S. toxytricini encodes the functional ACC enzyme subunits to be Biotinylated.

Anesth Analg. 2009 Oct; 109(4): 1318-22
Fukuda T, Hisano S, Tanaka M

BACKGROUND: Nociceptive behaviors might attenuate pain sensation. Phosphorylation of extracellular signal-regulated kinase (pERK) was recently reported to be induced by noxious stimuli in dorsal horn neurons. We investigated, in a formalin test, whether pERK of the dorsal horn is affected by licking. METHODS: Twenty-four adult male rats were divided into four groups: control, formalin test, restricted control, and restricted formalin test. Ten percent formalin was injected subcutaneously into the left rear paw of the formalin test and restricted formalin test groups. The control and formalin test group rats were kept in a clear plastic chamber, whereas the restricted control and restricted formalin test group rats were kept in a modified-restraint, pipe-shaped chamber. All rats were killed after 25 min. Twelve sections of the lumbar spinal cord were processed for p-ERK immunohistochemistry using the avidin-Biotin peroxidase method. RESULTS: The number of p-ERK positive cells in the restricted formalin test group was significantly higher than in the other three groups in the ipsilateral-side superficial dorsal horn (P < 0.05). However, there was no significant difference between the formalin test group and the two control groups in pERK expression. CONCLUSION: Licking decreased pERK of the spinal cord of the formalin test group. The findings suggested that licking attenuated the pain of the formalin test.

Hepatogastroenterology. 2009 Jul-Aug; 56(93): 1163-8
Liu F, Wang X, Yang L, Jiang B

BACKGROUND/AIMS: To develop an optimized formula for more stable and effective coupling of albumin microbubbles (MBs) to monoclonal antibodies (mAbs) using a Biotin-avidin system. METHODOLOGY: Biotin modified albumin MBs were first linked with avidin (Av) followed by treatment with Biotinylated mAbs. Each step was monitored using flow cytometry, and the results were summarized with an optimized formula. A hepatocellular carcinoma (HCC) and a normal human hepatocyte cell line were used to examine the effectiveness of this novel linkage strategy. RESULTS: The present experiments resulted in 96.05% of MBs bound to their microbubble shells. Av-Bio-MBs were conjugated to mAbs specific for the Hab18G/CD147 cell line. In vitro, CD147-specific MBs were found to bind to HCC cells, but not normal human hepatocyte cells. After exposure to Hab18G rosette-blocking mAb solution, few targeted MBs bound to HCC cells. CONCLUSIONS: Conjugation of MBs with Biotinylated mAbs forming an Av-Bio-MB system is a novel and attractive tool for HCC-targeting and molecular imaging.

J Am Chem Soc. 2009 Oct 14; 131(40): 14237-9
Koyfman AY, Braun GB, Reich NO

We present two strategies for attaching self-assembled DNA arrays to the surfaces of cells. Our first approach uses Biotin-streptavidin interactions to bind DNA architectures to Biotinylated cells. The second approach takes advantage of specific antibody-cell surface interactions, conjugated arrays and the subsequent binding to native epidermal growth factor receptors expressed on cancer cells. DNA array-cell surface interactions were visualized by fluorescence, confocal microscopy, and scanning electron microscopy. This novel application of DNA nanoarrays provides strategies to specifically label cell surfaces with micrometer-sized patches, bind cells onto a designed functionalized DNA scaffold, engineer cell/cell networks into microtissues, and deliver materials to cell surfaces.

Ann Diagn Pathol. 2009 Oct; 13(5): 313-21
Zyada MM, Grawish ME, Elsabaa HM

The expression of cyclooxygenase 2 (COX-2) is induced by growth factors, tumor promoters, and cytokines. It is correlated with carcinogenesis and apoptosis inhibition. This study was designed to investigate the expression of COX-2 and BCl-2 and to correlate their expressions with the clinicopathologic features in the mucoepidermoid carcinoma (MEC). The expression of COX-2 and BCl-2 proteins was investigated in 16 archival tumor tissues of MEC using the streptavidin-Biotin complex technique. Clinical information was obtained through the computerized retrospective database from the tumor registry between 2001 and 2007. It revealed that grading system of MEC did not correlate with the presence or absence of node metastasis. The expression of COX-2 and BCl-2 was variably expressed in all the examined specimens. COX-2 and BCl-2 immunoreactivity was observed mainly in the cytoplasm of neoplastic cells. As regard the clinicopathologic parameters, there was no significant difference in expression rates of COX-2 in patients among age, sex, and MEC grades (P > .05). However, the expression of COX-2 in node-positive tumors was significantly higher than that of node-negative tumors (P = .001). For BCL-2 expression, there was no significant difference in expression rates of BCl-2 in patients among age, sex, site, clinical stage, and lymph node metastasis (P > .05), whereas a high significant difference was observed between BCl-2 staining index and MEC grades (P = .027). Moreover, there is a positive correlation between COX-2 expression and BCL-2 staining index (P = .000). COX-2 is a good predictor for lymph node metastasis as well as ideal therapeutic target for the prevention or treatment of MEC. BCl-2 and COX-2 are potentially useful prognostic markers for MEC.

Ann Diagn Pathol. 2009 Oct; 13(5): 308-12
de Sousa FA, Paradella TC, Carvalho YR, Rosa LE

Several epidemiologic studies have shown the malignant transformation potential of oral lichen planus; however, this potential is subject of much controversy. To evaluate the expression of proteins related to the cell proliferation and apoptosis processes in oral lichen planus, we compared oral lichen planus with oral squamous cell carcinoma. Twenty-four cases of each lesion were submitted according to streptavidin-Biotin technique to evaluate the immunohistochemical expression of proliferating cell nuclear antigen, p53, bax, and bcl-2 proteins. chi(2) test showed no statistically significant differences between the expression of p53, bax, and bcl-2 in oral lichen planus and oral squamous cell carcinoma (P > .05). However, the expression of proliferating cell nuclear antigen was significantly lower in oral lichen planus than in oral squamous cell carcinoma (P < .05). No statistically significant differences between the expression of p53, bax, and bcl-2 in oral lichen planus and oral squamous cell carcinoma were observed, which may be an evidence of the potential of malignant transformation of oral lichen planus.