A series of novel conjugates of aspirin with natural phenolic acid antioxidants connected through a diol linker were designed and synthesized as potential bifunctional agents combining antioxidant and anti-inflammatory activity for reducing gastrointestinal toxicity. In general, the conjugates were found to be efficient antioxidants and many of them demonstrated much more potent anti-inflammatory activity than aspirin. Among them, 5a and 5b which bear the best anti-inflammatory activity exhibited significantly reduced ulcerogenic potency and toxicity compared to aspirin. However, it is evident that the anti-inflammatory activity of these dual-acting molecules in vivo, was not simply consistent with their antioxidant ability in vitro.

Human small C-terminal domain phosphatase 1 (Scp1) modulates the phosphorylation state of the C-terminal domain (CTD) of eukaryotic RNA polymerase II (RNAP II), with preference for phosphorylated Ser5 in the tandem heptad repeats of the CTD. Additionally, Scp1 was identified as a conserved regulator of neuronal stem cell development. Scp1 is a member of haloacid dehalogenase (HAD) superfamily, whose catalysis depends on a Mg(2+) ion and a DXDX(T/V) motif. The first Asp of the motif is identified as the nucleophile that is subject to phosphorylation leading to a phosphoryl-aspartate intermediate. This high-energy mixed anhydride intermediate is subsequently hydrolyzed to regenerate the enzyme. In the present study, we successfully captured the phosphoryl-aspartate intermediate in the crystal structure of an Scp1D206A mutant soaked with para-nitrophenyl phosphate (pNPP), providing strong evidence for the proposed mechanism. Furthermore, steady-state kinetic analysis of a variety of Scp1 mutants revealed the importance of Asp206 in Mg(2+) coordination mediated by a water molecule. Overall, we captured the snapshots of the phosphoryl transfer reaction at each stage of Scp1-mediated catalysis. Through structural based sequence alignment, we show that the spatial position of the D206 side chain is strictly conserved throughout HAD family. Our results strongly suggest that Asp206 and its equivalent residues in other HAD family members play important structural and possible mechanistic roles.

Positive behavioral responses to attractive faces have led neuroscientists to investigate underlying neural mechanisms in a "reward circuit" that includes brain regions innervated by dopamine pathways. Using male faces ranging from attractive to extremely unattractive, disfigured ones, this study is the first to demonstrate heightened responses to both rewarding and aversive faces in numerous areas of this putative reward circuit. Parametric analyses employing orthogonal linear and nonlinear regressors revealed positive nonlinear effects in anterior cingulate cortex, lateral orbital frontal cortex (LOFC), striatum (nucleus accumbens, caudate, putamen), and ventral tegmental area, in addition to replicating previously documented linear effects in medial orbital frontal cortex (MOFC) and LOFC and nonlinear effects in amygdala and MOFC. The widespread nonlinear responses are consistent with single cell recordings in animals showing responses to both rewarding and aversive stimuli, and with some human fMRI investigations of non-face stimuli. They indicate that the reward circuit does not process face valence with any simple dissociation of function across structures. Perceiver gender modulated some responses to our male faces: Women showed stronger linear effects, and men showed stronger nonlinear effects, which may have functional implications. Our discovery of nonlinear responses to attractiveness throughout the reward circuit echoes the history of amygdala research: Early work indicated a linear response to threatening stimuli, including faces; later work also revealed a nonlinear response with heightened activation to affectively salient stimuli regardless of valence. The challenge remains to determine how such dual coding influences feelings, such as pleasure and pain, and guides goal-related behavioral responses, such as approach and avoidance.

Although dwarf genes have been widely used to improve lodging resistance and enhance harvest index in cereal crops, lodging is still a serious problem in rapeseed (Brassica napus) production. A semi-dwarf B. napus mutant, ds-1, was identified through EMS mutagenesis of a microspore-cultured DH line. The mutant had a significant reduction in height due to a lower first branch position and shorter internodes when compared with wild-type cultivars. This dwarfism was inherited as a single semi-dominant gene, ds-1. DS-1 locus was mapped to chromosome A6, and co-segregated with a microsatellite marker BnEMS1125 derived from the gene BnRGA. BnRGA encodes a DELLA protein that functions as a GA signaling repressor. The expression of a mutant BnRGA allele from ds-1, Bnrga-ds, caused dwarf phenotypes in Arabidopsis. Comparative sequencing of RGA open-reading frames (ORFs) of ds-1 and wild-type cultivars revealed a single proline (P)-to-leucine (L) substitution that may lead to a gain-of-function mutation in GA signaling. The expression of the Arabidopsis homolog, Atrga-ds, bearing this site-directed mutation also rendered dwarf phenotypes in Arabidopsis, which demonstrated that the P-to-L mutation in the VHYNP motif of Bnrga-ds is responsible for the dwarfism. A yeast two-hybrid assay confirmed that this mutation inhibited the interaction between Bnrga-ds/Atrga-ds and the GA receptor, AtGID1A, in the presence of GA(3), suggesting that the conserved proline residue in the VHYNP motif of DELLA protein directly participates in DELLA-GID1 interaction. Identification and characterization of the dwarf gene ds-1 will facilitate its utilization in improving lodging resistance in Brassica breeding.

Drug-induced malfunction of nucleus accumbens (NAc) neurons underlies a key pathophysiology of drug addiction. Drug-induced changes in intrinsic membrane excitability of NAc neurons are thought to be critical for producing behavioral alterations. Previous studies demonstrate that, after short-term (2 d) or long-term (21 d) withdrawal from noncontingent cocaine injection, the intrinsic membrane excitability of NAc shell (NAcSh) neurons is decreased, and decreased membrane excitability of NAcSh neurons increases the acute locomotor response to cocaine. However, animals exhibit distinct cellular and behavioral alterations at different stages of cocaine exposure, suggesting that the decreased membrane excitability of NAc neurons may not be a persistent change. Here, we demonstrate that the membrane excitability of NAcSh neurons is differentially regulated depending on whether cocaine is administered contingently or noncontingently. Specifically, the membrane excitability of NAcSh medium spiny neurons (MSNs) was decreased at 2 d after withdrawal from either 5 d intraperitoneal injections (15 mg/kg) or cocaine self-administration (SA). At 21 d of withdrawal, the membrane excitability of NAcSh MSNs, which remained low in intraperitoneally pretreated rats, returned to a normal level in SA-pretreated rats. Furthermore, after a reexposure to cocaine after long-term withdrawal, the membrane excitability of NAcSh MSNs instantly returned to a normal level in intraperitoneally pretreated rats. Conversely, in SA-pretreated rats, the reexposure elevated the membrane excitability of NAcSh MSMs beyond the normal level. These results suggest that the dynamic alterations in membrane excitability of NAcSh MSNs, together with the dynamic changes in synaptic input, contribute differentially to the behavioral consequences of contingent and noncontingent cocaine administration.

BACKGROUND: The aberrant expression of microRNAs (miRNAs) is associated with a variety of diseases including cancers. In the present study, the miRNA expression profile was examined in astrocytoma, a malignant and prevalent intracranial tumour in adults. METHODS: We screened the expression profile of 200 miRNAs in a training sample set consisting of 84 astrocytoma samples and 20 normal adjacent tissue (NAT) samples using the method of stem-loop quantitative RT-PCR. The significantly altered miRNAs were validated in another independent sample set consisting of 40 astrocytoma samples and 40 NAT samples. The correlation of the miRNA levels with survival in astrocytoma samples was estimated by performing Kaplan-Meier survival analysis and univariate/multivariate Cox proportional hazard regression analysis. RESULTS: After a two-phase selection and validation process, seven miRNAs were found to have a significantly different expression profile in astrocytoma samples upon comparison to the NAT samples. Unsupervised clustering analysis further revealed the great potential of the 7-miRNA profile to differentiate between tumours and normal brain tissues. The down-regulation of hsa-miR-137 in astrocytomas was shown to be associated with advanced clinical stages of this disease. Using Kaplan-Meier survival analysis we showed that low expression of hsa-miR-181b or hsa-miR-106a, or high expression of hsa-miR-21 was significantly associated with poor patient survival. Moreover, Cox proportional hazard regression analysis revealed that this prognostic impact was independent of other clinicopathological factors. CONCLUSIONS: Our results suggest a great potential for the use of miRNA profiling as a powerful diagnostic and prognostic marker in defining the signature of astrocytomas and in predicting the post-surgical outcome.

Chiral compounds usually behave enantioselectively in phyto-biochemical processes. Imidazolinones are a class of chiral herbicides that are widely used. They inhibit branched-chain amino acid biosynthesis in plants by targeting acetolactate synthase (ALS). It has been reported that the imidazolinone enantiomers show different inhibiting activities to maize (Zea mays L.) seedlings and ALS. However, to date, the mechanism of enantioselective inhibition of imazethapyr (IM) on ALS activity has not been well studied. In this study, pure enantiomers of IM were used for characterizing their differences in activity to ALS. Computational molecular docking was performed to discover the molecular interaction between IM enantiomers and ALS at the first time. Results showed that the IM enantiomers enantioselectively suppressed the in vitro and in vivo ALS activity of maize leaves. R-(-)-IM was more active than S-(+)-IM. The in vivo ALS activity study showed only a 2-fold difference between R-(-)-IM and S-(+)-IM. Quite different from the in vivo study, the in vitro study showed that the difference in inhibition between the enantiomers fell sharply as concentration increased. At the lowest concentration of 40 mug L(-1), R-(-)-IM appeared 25 times more active than S-(+)-IM, but only 7 times at 200 mug L(-1). At the highest concentration of 25 mg L(-1), in vitro ALS activity was almost completely inhibited by S-(+)-, R-(-)-IM and (+/-)-IM, there was only 1.1 times differences between S-(+)- and R-(-)-IM. Molecular modeling results provide the rational structural basis to understand the mechanism of enantioselective inhibition of IM on ALS activity.

Nucleotide binding site (NBS)-leucine-rich repeat (LRR) genes belong to the largest class of disease-resistance gene super groups in plants, and their intra- or interspecies nucleotide variations have been studied extensively to understand their evolution and function. However, little is known about the evolutionary patterns of their copy numbers in related species. Here, 129, 245, 239 and 508 NBSs were identified in maize, sorghum, brachypodium and rice, respectively, suggesting considerable variations of these genes. Based on phylogenetic relationships from a total of 496 ancestral branches of grass NBS families, three gene number variation patterns were categorized: conserved, sharing two or more species, and species-specific. Notably, the species-specific NBS branches are dominant (71.6%), while there is only a small percentage (3.83%) of conserved families. In contrast, the conserved families are dominant in 51 randomly selected house-keeping genes (96.1%). The opposite patterns between NBS and the other gene groups suggest that natural selection is responsible for the drastic number variation of NBS genes. The rapid expansion and/or contraction may be a fundamentally important strategy for a species to adapt to the quickly changing species-specific pathogen spectrum. In addition, the small proportion of conserved NBSs suggests that the loss of NBSs may be a general tendency in grass species.

The macromonomer of 2-hydroxyethyl methyacrylate-caprolactone (HPCL) was synthesized by the ring-opening polymerization (ROP) of epsilon-caprolactone, which was initiated by 2-hydroxyethyl methyacrylate (HEMA). Then, the graft terpolymers of NIPAAm-co-AAc-co-HEMA-g-PCL (PHNA-CL) with varying mole ratios were subsequently synthesized by free radical polymerization of HEMA-PCL, N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc). PHNA-CL was further self-assembled in different types of solvent. All the as-prepared copolymers were characterized by (1)H NMR, FT-IR and GPC. Micellization behaviors of micelles were studied by TEM and DLS. The micelles exhibited a phase transition temperature which can be readily adjusted by changing pH value of the micellization system. Micelle loaded with doxorubicin (DOX) was used to evaluate the drug release behavior. The release of DOX from micelles could be controlled by changing pH value and temperature in buffer solutions. The micelles are potentially to be used as a new anticancer drug carrier for intracellular delivery.

BACKGROUND: It remains to be established whether spinal cord ischemic tolerance can be induced by limb remote ischemic preconditioning (RIPC), and the mechanisms underlying the neuroprotective effects of RIPC on the spinal cord need to be clarified. METHODS: Spinal cord ischemia was studied in New Zealand White rabbits. In experiment 1, all rabbits were subjected to 20-min spinal cord ischemia by aortic occlusion. Thirty minutes before ischemia, rabbits were subjected to sham intervention or RIPC achieved by bilateral femoral artery occlusion (10 min ischemia/10 min reperfusion, two cycles). Dimethylthiourea (500 mg/kg, intravenously), a hydroxyl radical scavenger, or vehicle was given 1 h before RIPC. Antioxidant enzyme activity was measured along with spinal cord histology and neurologic function. In experiment 2, rabbits were subjected to spinal cord ischemia, with or without RIPC. In addition, rabbits were pretreated with various doses of hexamethonium. RESULTS: RIPC improved neurologic function and reduced histologic damage. This was associated with increased endogenous antioxidant activity. Dimethylthiourea inhibited the protective effects of RIPC. In contrast, there was no effect of hexamethonium on the protective effect of RIPC. CONCLUSIONS: An initial oxidative stress acts as a trigger to upregulate antioxidant enzyme activity, rather than the neural pathway, and plays an important role in the formation of the tolerance against spinal cord ischemia by limb RIPC.

BACKGROUND: Neuromuscular blocking agents are an integral component of general anesthesia. In addition to their intended pharmacologic target on skeletal muscle nicotinic receptors, undesirable airway effects (i.e., bronchoconstriction) can result from neuromuscular blocking agents'; affinity for airway muscarinic receptors. We questioned whether two new members of a bisquaternary nondepolarizing muscle relaxant family, gantacurium and CW002, demonstrated detrimental effects of airway muscarinic receptors using an in vivo model in guinea pig airways. METHODS: Urethane-anesthetized male guinea pigs were ventilated through a tracheostomy with continuous digital recordings of pulmonary inflation pressure and heart rate. The dose for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium was defined in the guinea pig. Transient and reproducible changes in pulmonary inflation pressure and heart rate were recorded after vagal nerve stimulation or intravenous injection of acetylcholine before and after pretreatment with cumulatively increasing concentrations of gantacurium, CW002, cisatracurium or a single concentration of rapacuronium. RESULTS: The doses for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium were 0.064 +/- 0.006, 0.012 +/- 0.0006, 0.10 +/- 0.003, and 0.31 +/- 0.05 mg/kg, respectively. Gantacurium, CW002, and cisatracurium were without effects on baseline pulmonary inflation pressures and were devoid of significant interactions with M2 and M3 muscarinic receptors in vivo. CONCLUSION: These findings suggest that gantacurium and CW002 are devoid of significant effects at airway muscarinic receptors particularly M3 receptors on bronchial smooth musculature at doses several fold higher than those required for functional muscle paralysis.

Pertussis continues to circulate in Chinese communities and older children, adolescents and adults are sources of infection for unprotected infants. Two studies conducted in Jiangsu Province in the People's Republic of China assessed the immunogenicity, reactogenicity and safety of Boostrix(), a combined reduced antigen content diphtheria-tetanus-acellular pertussis vaccine (dTpa) when administered as a booster dose to children 6 to 8 years of age. Immunogenicity was assessed before and one month after vaccination in a subset. Reactogenicity was assessed over a 4-day follow-up using diary cards. A total of 690 Chinese subjects were enrolled. Boostrix() was well tolerated. One month after the booster dose, 100% of dTpa recipients had seroprotective antibody concentrations against diphtheria and tetanus. The percentage of subjects with a response against pertussis antigens (using locally defined cut-offs) was 91.9% for pertussis toxoid, 98.8% for filamentous hemagglutinin, and 100% for pertactin. The exploratory analysis showed no statistically significant differences between dTpa or diphtheria-tetanus vaccine in terms of the percentage of subjects with seroprotective antibodies against diphtheria or tetanus. These studies demonstrate that Boostrix() is well tolerated and immunogenic when administered as a booster dose to 6 to 8 year old Chinese children previously immunized with a combined diphtheria-tetanus-pertussis vaccine. Introduction of dTpa into the routine Chinese immunization schedule would provide booster vaccination against pertussis without the addition of further injections into the Chinese vaccination schedule and is likely to promote improved pertussis control in older children.

Recognition of the AUG start codon on mRNAs during translation initiation in eukaryotes occurs in a pre-initiation complex that includes small ribosomal subunits and multiple translation initiation factors. The complexity of this process and the lack of appropriate tools have prevented its genetic study in multi-cellular organisms. Here we describe a genetic system in the nematode C. elegans to study how the AUG start codon is selected. We have generated a sensitive reporter assay that allows for the isolation of mutants with reduced fidelity to recognize the AUG start codon. Two mutants were identified to have dominant missense mutations in iftb-1 which encodes the beta subunit of eIF2 (eIF2beta). Both mutations occur in a conserved region located outside of the C2-C2 zinc finger domain where yeast SUI3 mutations are localized in S. cerevisiae eIF2beta. C. elegans iftb-1, as well as mutant eIF2betas carrying the equivalent SUI3 mutations, are able to initiate translation at non-AUG codons that retain two potential base-pairing interactions with the anticodon of the initiator methionyl tRNA. These analyses further support the critical role of eIF2beta in start codon selection, and two functional domains within eIF2beta are likely involved, one defined by our C. elegans mutants and the other by the yeast SUI3 mutants.

This work studied the role of cyclic AMP responsive element binding protein (CREB) in the up-regulation of M(1) muscarinic acetylcholine receptor (M(1) receptor) density by sarsasapogenin in CHO cells transfected with M(1) receptor gene (CHOm1 cells). During cell aging, sarsasapogenin elevated M(1) receptor density as well as CREB and phosphor-CREB (pCREB) levels. CREB peaked earliest, followed by pCREB and M(1) receptor density peaked last. When CREB synthesis was blocked by antisense oligonucleotides, the elevation effect of sarsasapogenin on M(1) receptor density was abolished. These results suggest that sarsasapogenin up-regulates M(1) receptor density in aged cells by promoting CREB production and phosphorylation. Furthermore, the results support the hypothesis that pCREB regulates M(1) receptor gene expression through heterodimer formation.

OBJECTIVE: To observe the therapeutic effect of tranquilizing and allaying excitement needling method on insomnia of heart and spleen deficiency and the effect of brain blood flow. METHODS: Sixty cases were randomly divided into a tranquilizing and allaying excitement needling method group (observation group) and an eight confluence points selected group (control group), 30 cases in each group. The observation group was treated by acupuncture at Sishencong (EX-HN 1), Shenmen (HT 7), and Sanyinjiao (SP 6) with tranquilizing and allaying excitement needling method. The control group was treated by acupuncture at Shenmai (BL 62) and Zhaohai (KI 6). Their therapeutic effects and changes of brain blood flow were observed. RESULTS: The total effective rate was 93.3% (28/30) in the observation group which was better than 83.3% (25/30) in the control group (P < 0.05). After treatment, the peak velocity of systolic (Vp) and diastolic blood flow velocity (Vd) of middle cerebral artery, basilar artery and vertebral artery were increased in the both groups (P < 0.01, P < 0.05), with more obvious increase in the observation group (P < 0.01, P < 0.05), except the Vd of left vertebral artery. CONCLUSION: Both the tranquilizing and allaying excitement needling method and the eight confluence points selected needling method can improve the clinical signs and symptoms. Meanwhile, the therapeutic effect of acupuncture is related with improvement of brain blood flow. However, the tranquilizing and allaying excitement needling method has better therapeutic effect on insomnia of heart and spleen deficiency.

CARM1/PRMT4 is a member of the protein arginine methyltransferase (PRMT) family. CARM1 as a transcriptional coactivator plays an active role on mammalian genes. Here, we show that CARM1 can be recruited to the promoter of myogenin gene to enhance its transcriptional activation via PCAF at the early stage of TPA-induced RD cell differentiation. By adding adenosine dialdehyde, AdOx, to inhibit the PRMT in RD cells, the TPA-induced recruiting of p300, PCAF and the Brg1 at the myogenin promoter is abolished and myogenic differentiation is blocked. More specifically, the expression of PCAF and its nucleation are prohibited when CARM1 is knockdown by its specific siRNA. We suggest that the physical interaction of CARM1 and PCAF is likely pivotal for the activation of PCAF in the downstream of CARM1 pathway for inducing myogenin under TPA-induced differentiation. The findings shed lights on novel therapeutic targets in the treatment of rhabdomyosarcoma patients. J. Cell. Biochem. (c) 2010 Wiley-Liss, Inc.

Proteins encoded by the NAC gene family constitute one of the largest plant-specific transcription factors, which have been identified to play many important roles in both abiotic and biotic stress adaptation, as well as in plant development regulation. In the current paper, a full-length cDNA sequence of a novel wheat NAC gene, designated as TaNAC4, was isolated using in silico cloning and the reverse transcription PCR (RT-PCR) methods. TaNAC4 sharing high homology with rice OsNAC4 gene was predicted to encode a protein of 308 amino acid residues, which contained a plant-specific NAC domain in the N-terminus. Transient expression analysis indicated that the deduced TaNAC4 protein was localized in the nucleus of onion epidemical cells. Yeast one-hybrid assay revealed that the C-terminal region of the TaNAC4 protein had transcriptional activity. The expression of TaNAC4 was largely higher in the wheat seedling roots, than that in leaves and stems. TaNAC4 transcript in wheat leaves was induced by the infection of strip rust pathogen, and also by exogenous applied methyl jasmonate (MeJA), ABA and ethylene. However, salicylic acid (SA) had no obvious effect on TaNAC4 expression. Environmental stimuli, including high salinity, wounding, and low-temperature also induced TaNAC4 expression. These results indicate that this novel TaNAC4 gene functions as a transcriptional activator involved in wheat response to biotic and abiotic stresses.

Human CMTM is a novel gene family consisting of CKLF and CMTM1-8. CMTM4 is the most conserved gene and has three RNA splicing forms designated as CMTM4-v1, -v2 and -v3, but in many types of tissue and cell lines, only CMTM4-v1 and -v2 could be detected. CMTM4-v2 is the full length cDNA product, which has been highly conserved during e volution. CMTM4-v1 and - v2 a re b roadly expressed in normal types of tissue. They are distributed on the cell membrane and across the cytoplasm in a speckled pattern. Overexpression of CMTM4-v1 and -v2 can inhibit HeLa cell growth via G2/M phase accumulation without inducing apoptosis. Therefore, CMTM4 might be an important gene involved in cell growth and cell cycle regulation.

Surgical treatment of complex severe spinal deformity, involving a scoliosis Cobb angle of more than 90 degrees and kyphosis or vertebral and rib deformity, is challenging. Preoperative two-dimensional images resulting from plain film radiography, computed tomography (CT) and magnetic resonance imaging provide limited morphometric information. Although the three-dimensional (3D) reconstruction CT with special software can view the stereo and rotate the spinal image on the screen, it cannot show the full-scale spine and cannot directly be used on the operation table. This study was conducted to investigate the application of computer-designed polystyrene models in the treatment of complex severe spinal deformity. The study involved 16 cases of complex severe spinal deformity treated in our hospital between 1 May 2004 and 31 December 2007; the mean +/- SD preoperative scoliosis Cobb angle was 118 degrees +/- 27 degrees . The CT scanning digital imaging and communication in medicine (DICOM) data sets of the affected spinal segments were collected for 3D digital reconstruction and rapid prototyping to prepare computer-designed polystyrene models, which were applied in the treatment of these cases. The computer-designed polystyrene models allowed 3D observation and measurement of the deformities directly, which helped the surgeon to perform morphological assessment and communicate with the patient and colleagues. Furthermore, the models also guided the choice and placement of pedicle screws. Moreover, the models were used to aid in virtual surgery and guide the actual surgical procedure. The mean +/- SD postoperative scoliosis Cobb angle was 42 degrees +/- 32 degrees , and no serious complications such as spinal cord or major vascular injury occurred. The use of computer-designed polystyrene models could provide more accurate morphometric information and facilitate surgical correction of complex severe spinal deformity.

HAb18G is a recently identified hepatoma-associated antigen and its association with tumor growth, invasion, and angiogenesis has been studied in a variety of tumors. However, its role in the tumor progression of breast cancer has not been explored. HAb18G expression was examined by immunohistochemistry in pathological sections of 1,637 breast tissue samples and by in situ hybridization in 41 cases of invasive breast carcinomas (BC). While not detected in any cases of tumor-like conditions or benign tumors of breast, and only rarely in normal tissue (4.4%), HAb18G expression was gradually up-regulated from atypical ductal hyperplasia (27.3%), to ductal carcinoma-in situ (59.8%), and to BC (61.4%) (P < 0.01). Its expression in BC was correlated positively with C-erbB-2 expression and histologic grade (P < 0.001), and negatively with the expression of estrogen and progesterone receptors (P < 0.001). Significant differences of expression were also identified among the subgroups of BC examined: in decreasing order from invasive micropapillary carcinoma, ductal carcinoma, lobular carcinoma, papillary carcinoma, medullary carcinoma, to mucinous adenocarcinoma (P = 0.001), corresponding to their known clinical aggressiveness. In an expanded group of 186 BC patients with proper follow up, our previous findings were confirmed: HAb18G expression was significantly associated with local recurrence, distant metastasis and tumor mortality (P < 0.01). We also demonstrated that up-regulated tumor expression of HAb18G was a significant predictor of reduced disease progression-free survival rate and a shorter overall survival, independent of systemic therapies. In conclusion, this study suggests that HAb18G expression is associated with BC progression and prognosis. Further evaluation of this new marker in breast cancer is indicated.