Prognostic significance of preoperative albumin-to-globulin ratio in patients with cholangiocarcinoma.

BACKGROUND: This study aimed to assess the prognostic value of the serum albumin to globulin ratio (AGR) in cholangiocarcinoma patients after surgery. METHODS: We retrospectively enrolled 123 cholangiocarcinoma patients who underwent surgical treatment between June 2003 and September2014 at the Third Affiliated Hospital of Sun Yat-sen University. Univariate and multivariate analyses using the Cox regression model were performed to determine the prognostic value of AGR. RESULTS: Univariate analysis suggested that AGR was a predictive factor for (overall survival) OS but not for recurrence free survival (RFS). After adjustment for other risk factors, multivariate analysis showed that AGR remained independently associated with OS. The optimal cut-off point for AGR was determined to be 1.44. Kaplan-Meier curves showed that there was a significantly lower mean survival time in the low AGR group compared to the high AGR group. A low AGR was found to be significantly associated with high alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin levels and an advanced American Joint Committee on Cancer TNM stage, but a low hemoglobin level. CONCLUSION: In summary, patients with higher AGRs have better outcomes than those with lower AGRs. Preoperative AGR can be a reliable marker for evaluating the prognosis of cholangiocarcinoma patients.

Prophylactic inhalation of L-alanyl-L-glutamine enhances heat shock protein 72 and attenuates endotoxin-induced lung injury in rats.

Studies have demonstrated that heat shock protein 70 (HSP70) plays an important role in the protection of stressed organisms. The development of strategies for enhancing HSPs expression may provide novel means of minimizing inflammatory lung conditions, such as acute lung injury. This study aimed to examine the effect of L-alanyl-L-glutamine (GLN) inhalation in enhancing pulmonary HSP72 (inducible HSP70) expression and attenuating lung damage in a model of acute lung injury induced by lipopolysaccharide (LPS) inhalation. The experimental rats were randomly assigned to one of four experimental groups: (1) NS: saline inhalation; (2) NS-LPS: pretreatment by saline inhalation 12 h before LPS inhalation; (3) GLN: glutamine inhalation; (4) GLN-LPS: pretreatment by glutamine inhalation 12 h before LPS inhalation. The results show that GLN compared with saline administration, led to significant increase in lung HSP72 both in non LPS-treated rats and LPS-treated rats. In LPS-treated rats, pretreatment by GLN inhalation produced less lung injury as evidenced by the decrease in lung injury score and dramatic decrease in lactate dehydrogenase (LDH) activity and polymorphonuclear leukocyte cell differentiation counts (PMN %) in the bronchoalveolar lavage fluid. The study indicates that prophylactic glutamine inhalation associated with the enhancement of HSP72 synthesis attenuates tissue damage in experimental lung injury.

Angiomotin decreases lung cancer progression by sequestering oncogenic YAP/TAZ and decreasing Cyr61 expression.

Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic Yes-associated protein/transcriptional co-activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential role in tumor progression. However, the functional role of AMOT in lung cancer remains unknown. This study aimed to identify the patho-physiological characteristics of AMOT in lung cancer progression. Results revealed that AMOT expression was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial-mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreased cytoplasmic sequestration and increased nuclear translocation of oncogenic co-activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61. Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent. Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma in vivo. These findings suggest that AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer.

MTAP is an independent prognosis marker and the concordant loss of MTAP and p16 expression predicts short survival in non-small cell lung cancer patients.

OBJECTIVES: Methylthioadenosine phosphorylase (MTAP), a ubiquitously expressed protein, plays important roles in purine biosynthesis. Locating near to each other on chromosome 9p21-22, codeletion of the MTAP and p16(Ink4A) genes have been reported in non-small cell lung cancer (NSCLC). The aim of this study is to determine the respective prognostic value of MTAP and p16 by considering their correlation in NSCLC patients. MATERIALS AND METHODS: We analyzed MTAP and p16 protein expression by immunohistochemical staining on 99 NSCLC tissue microarray samples. The association between MTAP and p16 expression levels and prognosis were analyzed using the Kaplan-Meier method and Cox proportional hazards model for prognosis. RESULTS: Patients with a low MTAP expression level had poor overall survival (P = 0.010) and disease-free survival (P = 0.002). Low p16 expression indicated a trend toward poor overall survival (P = 0.138) and disease-free survival (P = 0.199). There was a significant positive correlation between MTAP and p16 expression levels (Spearman's ρ = 0.402, P < 0.001). By multivariate analyses, the MTAP expression level retained its independent prognostic power and p16 expression loss of the correlation with prognosis. Concordant loss of MTAP and p16 expression was observed in 24 out of 99 patients (24.2%). Patients with concordant loss of MTAP and p16 expression had the worst prognosis compared to patients with high expression of both markers. CONCLUSION: MTAP expression is an independent prognostic factor and has greater prognostic significance than p16 expression in NSCLC. Concordant loss of MTAP and p16 expression indicates poor outcomes in lung cancer patients.

Endoplasmic reticulum ribosome-binding protein 1 (RRBP1) overexpression is frequently found in lung cancer patients and alleviates intracellular stress-induced apoptosis through the enhancement of GRP78.

Lung cancer is the leading cause of cancer deaths and is the most occurring malignancy worldwide. Unraveling the molecular mechanisms involved in lung tumorigenesis will greatly improve therapy. During early tumorigenesis, rapid proliferating tumor cells require increased activity of endoplasmic reticulum (ER) for protein synthesis, folding and secretion, thereby are subjected to ER stress. Ribosome-binding protein 1 (RRBP1) was originally identified as a ribosome-binding protein located on the rough ER and associated with unfolding protein response (UPR). In this report, we investigated the role of RRBP1 in lung cancer. RRBP1 was highly expressed in lung cancer tissue, as compared with adjacent normal tissues as assessed by immunohistochemistry (IHC) using lung cancer tissue array (n=87). Knockdown of RRBP1 by short-hairpin RNAs caused ER stress and significantly reduced cell viability and tumorigenicity. This effect was associated with a significant reduction in the expression of glucose-regulated protein 78 (GRP78). UPR regulator GRP78, an anti-apoptotic protein that is widely upregulated in cancer, has a critical role in chemotherapy resistance in some cancers. According to our results, cells with a higher level of RRBP1 were more resistant to ER stress. Ectopic expression of RRBP1 alleviated apoptosis that was induced by the ER-stress agent tunicamycin, 2-deoxy-D-glucose (2DG) or doxorubicin via enhancing GRP78 protein expression. A strong correlation was observed between the expression of RRBP1 and GRP78 in tumor biopsies using the database GSE10072. Our results also indicated that RRBP1 may involve in the regulation of mRNA stability of UPR components including ATF6 and GRP78. Taken together, RRBP1 could alleviate ER stress and help cancer cell survive. RRBP1 is critical for tumor cell survival, which may make it a useful target in lung cancer treatment and a candidate for the development of new targeted therapeutics.

TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer.

We integrated four gene expression profile data sets, namely two different pair-matched stage I lung adenocarcinoma data sets, secondary metastatic tumors vs benign tumors and lung tumor metastasizes to the brain, and we identified one kinase, T-LAK Cell-Originated Protein Kinase (TOPK), as a putative gene that promotes metastasis. To delineate the role of TOPK in lung cancer, we showed that overexpression of TOPK, but not a catalytically inactive form of TOPK, can enhance the migration and invasion of lung fibroblasts or cells with low TOPK expression. In addition, TOPK-induced cell migration was shown to be a PI3K/AKT-dependent event. TOPK concurrently promoted AKT phosphorylation at Ser(473) and decreased the phosphatase and tensin homolog (PTEN) levels, whereas TOPK knockdown had the reverse effects. LY294002, a PI3K inhibitor, did not inhibit the TOPK-induced decrease in PTEN, and co-expression of PTEN significantly reduced TOPK-induced AKT phosphorylation in a dose-dependent manner; these results indicate that the TOPK-mediated PTEN decrease has an upstream role in regulating PI3K/AKT-stimulated migration. Using immunohistochemical analysis of lung cancer tissue samples, we showed that a high TOPK expression level correlates strongly with reduced overall and disease-free survivals. Moreover, an inverse correlation between TOPK and PTEN expression was present and is consistent with the biochemical findings. Finally, a combination of high TOPK and low PTEN expression was inversely correlated with overall and disease-free survivals, independent of other pathologic staging factors. Our results suggest that TOPK is a potential therapeutic target in lung cancer that promotes cell migration by modulating a PI3K/PTEN/AKT-dependent signaling pathway; they also suggest that high TOPK expression, either alone or in combination with a low level of PTEN, may serve as a prognostic marker for lung cancer.

The mode of reproductive-derived Spink (serine protease inhibitor Kazal-type) action in the modulation of mammalian sperm activity.

The reproductive-derived serine protease inhibitor Kazal-type (Spink) has been identified in seminal plasma, and Spink-spermatozoa binding has been illustrated in many mammalian species including human. We used mice as experimental animal to study the mode of Spink action in the modulation of mammalian sperm activity. A Spink3-binding zone was cytochemically stained on the sperm head at apical hook separated from intact acrosome, whether the cells were capacitated or not. The Spink3-spermatozoa binding neither changed the population of cells in the uncapacitated, capacitated and acrosome-reacted status nor affected the capacitation-related protein phosphorylation and cell motility enhancement. Despite that, the Spink-spermatozoa interaction resulted in decreasing the intracellular calcium concentration ([Ca(2+)](i)) of the cell head and suppressing both the acrosome reaction induced by Ca(+2) ionophore A23187 and the cell fertility. Furthermore, Spink3 seen on the head of spermatozoa in the uterine cavity after coitus could be removed by the trypsin-like activity in the uterine fluid of oestrous females, and free Spink3 in the uterine cavity suppressed the protease activity. We integrated our data to shed light on the molecular mechanism of how Spink and its inhibiting protease are interplayed to modulate the activity of mammalian spermatozoa during their transit in the reproductive tract.

Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells.

This study is the first to analyse the soluble factors secreted by the bronchial epithelium after exposure to isophorone diisocyanate (IPDI) that are responsible for increasing migration and proliferation of primary normal human bronchial smooth muscle cells (BSMCs). We treated immortalised, nontumorigenic human bronchial epithelial cells (cell line BEAS-2B) and primary normal human bronchial epithelial cells (HBEC) with IPDI, and then collected the conditioned culture media (IPDI-BEAS-2B-CM and IPDI-HBEC-CM, respectively), which was added to BSMCs. Exposure of BEAS-2B cells and HBECs to IPDI increased interleukin (IL)-8 production. Culture of BSMCs with IPDI-BEAS-2B-CM and IPDI-HBEC-CM increased BSMC proliferation and migration, which are major features in asthma-related airway remodelling. Induction of BSMC proliferation and migration by IPDI-BEAS-2B-CM and IPDI-HBEC-CM was associated with increased focal adhesion kinase (FAK), Src, extracellular signal-regulated kinase (ERK)1/2 and AKT activation. Blocking FAK with a specific inhibitor significantly decreased BSMC migration and proliferation by inhibiting ERK1/2 activation. FAK and ERK1/2 inhibitor also decreased IPDI-BEAS-2B-CM-, IPDI-HBEC-CM- and recombinant human IL-8-mediated BSMC proliferation and migration, whereas blocking Rnd3 using small interfering RNA failed to affect BSMC proliferation, suggesting that Rnd3 was only involved in the regulation of BSMC migration. Our study suggests that inhibition of IL-8 or IL-8-mediated FAK/ERK/Rnd3 signalling is an attractive therapeutic target for IPDI-mediated asthma.

Hepatic migration of a catheter fragment followed by disconnection of a totally implantable venous access port.

Totally implantable venous access ports (TIVAPs) are frequently used in oncology patients who require long-term courses of chemotherapy. We report a silent, but potentially hazardous complication of catheter fracture and hepatic migration in a 64-year-old male. The patient presented with a painful, rapid swelling of subcutaneous tissue around the port area during a saline flush. A chest radiograph showed that the disconnected catheter had separated from the port and was no longer in its original location. A chest CT scan revealed that the disconnected catheter was found to be embolized to the right atrium, inferior vena cava and right hepatic vein. The patient was treated successfully with percutaneous transfemoral retrieval of the catheter under fluoroscopic guidance. To our knowledge, there have been no previous reports of migration of the fractured catheter of a TIVAP into the right hepatic vein. This case highlights that the integrity of TIVAPs should be ascertained before chemotherapeutic drugs are administered.

The impact of age on the demographic, clinical, radiographic characteristics and treatment outcomes of pulmonary tuberculosis patients in Taiwan.

BACKGROUND: The characteristics of pulmonary tuberculosis (TB) in the elderly are different from young patients. This leads to delay in diagnosis and higher mortality from TB in the aged population. The aim of this study was to investigate the impact of age on the demographic, clinical, radiographic characteristics, and treatment outcomes of pulmonary TB patients in Taiwan. MATERIALS AND METHODS: We performed a retrospective analysis of the medical charts and chest radiographs of 83 elderly (> or =60 years old) and 74 young (< 60 years old) culture-proven pulmonary TB patients from 1 August 2003 to 31 July 2006. RESULTS: Elderly patients showed lower frequencies of infectious TB contact history, alcoholism, cavity, and positive acid-fast bacilli sputum smears. In contrast, the elderly population had higher frequencies of chronic obstructive lung disease, heart failure, stroke, dyspnea, lower lung field involvement, pleural effusion and mortality. There were no differences between these two groups regarding sex, initial body weight, previous TB disease, hospital admission, diabetes mellitus, end-stage renal disease, neoplasm, liver cirrhosis, upper lung field involvement, cure, and treatment completion. Furthermore, age of 60 and older, lower initial body weight less than 50 kg, coexisting medical diseases, and extensive radiographic disease were factors independently associated with unfavorable outcomes. CONCLUSIONS: Elderly patients with pulmonary TB are more likely to present with negative sputum smears, cavity-negative lesions, lower lung field involvement and pleural effusion on chest radiographs. The prognosis is poor for the elderly pulmonary TB patients with lower body weight, coexisting medical diseases, and extensive radiographic disease.

Cancer aggregation and complex segregation analysis of families with female non-smoking lung cancer probands in Taiwan.

Previous studies have found that having a first-degree blood relative with lung cancer was a possible predictor of lung cancer risk, but some studies have indicated that the association is non-significant or only significant for a subset of the studied population. To determine the familial aggregation and whether there is any evidence for a gene controlling the susceptibility to developing lung cancer in female non-smokers, multiple logistic regression methods for estimating covariate effects and maximum likelihood segregation analyses were performed using data from 216 female non-smoking lung cancer probands (2328 individuals) in a population-based case-control study. Having a family history of lung cancer was found to be a significant predictor of lung cancer for non-smoking females (Adjusted Odds Ratio (OR)=5.7, 95% Confidence Interval (CI)=1.9-16.9). Having a female relative with lung cancer (adjusted OR=14.4, 95% CI=2.7-75.5) was more strongly associated with the lung cancer risk than was having a male relative with lung cancer. This association was stronger for probands aged less than 60 years at onset (adjusted OR=11.2, 95% CI=2.2-56.9). All of the Mendelian models fitted the data significantly better than the sporadic (no major type) model or the environmental model (P<0.00l). The Mendelian codominant models provided the best fit of the data for the early onset probands and showed a stronger effect for a major susceptibility locus for non-smoking lung cancer probands. The results of this study provide evidence that a rare autosomal codominant gene may influence the risk lung cancer in non-smoker and is responsible for the familial aggregation observed in non-smoking lung cancer patients.

Comparisons of tumor suppressor p53, p21, and p16 gene therapy effects on glioblastoma tumorigenicity in situ.

The mutation and/or deletion of tumor suppressor genes have been postulated to play a major role in the genesis and the progression of gliomas. In this study, the functional expression and efficacy in tumor suppression of 3 tumor suppressor genes (p53, p21, and p16) were tested and compared in a rat GBM cell line (RT-2) after retrovirus mediated gene delivery in vitro and in vivo. Significant reductions in tumor cell growth rate were found in p16 and p21 infected cells (60 +/- 12% vs 66 +/- 15%) compared to p53 (35 +/- 9%). In vitro colony formation assay also showed significant reductions after p16 and p21 gene delivery (98 +/- 5% vs 91 +/- 10%) compared to p53 (50 +/- 18%). In addition, the tumor suppression efficacy were investigated and compared in vivo. Retroviral mediated p16 and p21 gene deliveries in glioblastomas resulted in more than 90% reductions in tumor growth (92 +/- 26% vs 90 +/- 22%) compared to p53 (62 +/- 18%). Tumor suppressor gene insertions in situ further prolonged animal survival. Overall p16 and p21 genes showed more powerful tumor suppressor effects than p53. The results were not surprising, as p16 and p21 are more downstream in the cell cycle regulatory pathway compared to p53. Moreover, the mechanism involved in each of their suppressor effects is different. This study demonstrates the feasibility of using tumor suppressor genes in regulating the growth of glioma in vitro and in situ.

The heterogeneity in risk factors of lung cancer and the difference of histologic distribution between genders in Taiwan.

OBJECTIVE: The difference in histologic patterns of lung cancer between men and women in Taiwan may be associated with the heterogeneity in causal factors of lung cancer between the sexes. A sex- and age-matched case-control study was designed to investigate such a relationship. METHODS: Cases consisted of 236 male and 291 female incident cases with newly diagnosed and histologically confirmed primary carcinoma of the lung, and were compared to one or two individually matched controls. RESULTS: Cigarette smoking, occupations, and previous tuberculosis history were found to independently correlate with an elevated risk of squamous/small cell carcinoma and adenocarcinoma for male patients. However, there was little difference in the effect of these risk factors except smoking. The use of fume extractors in the kitchen, and the habit of waiting to fry after the fumes were emitted, separately explained the majority of the attributable fraction of female squamous/small cell carcinoma (28.2%) and adenocarcinoma (47.7%). With the exception of a kitchen with fume extractors and a clinical history of tuberculosis, the environmental causal factors of lung cancer were heterogeneous between these two histologic cell groups. CONCLUSIONS: Our results suggested that the causal factors of lung cancer might be specific for the type of tumor concerned. The gender-specific risk factors of lung cancer could partly explain the difference in cell-type distribution between men and women.

Hemodynamic response of modified fluid gelatin compared with lactated ringer's solution for volume expansion in emergency resuscitation of hypovolemic shock patients: preliminary report of a prospective, randomized trial.

The objective of this study was to compare the cardiac and hemodynamic responses to a rapid infusion of 1000 ml of modified fluid gelatin (group A) or 1000 ml of lactated Ringer's solution (group B) in emergency room patients suffering from shock. This prospective, randomized, open, noncrossover study was performed at a medical center university hospital in a surgical resuscitation room in the emergency department. The subjects were 34 patients with either hypovolemic or neurogenic shock who were admitted to the emergency room. A resuscitation protocol according to Advanced Trauma Life Support (ATLS) with an additional central venous line or Swan-Ganz catheters for hemodynamic monitoring was used. Physical parameters and hemodynamic variables were measured at baseline and 15 minutes, 30 minutes, and 1 hour after the infusion of each fluid. In both groups the mean arterial blood pressure (MAP), systolic and diastolic pressure, central venous pressure (CVP), and pulmonary artery occlusion pressure (PAOP) increased significantly. The CVP and PAOP increased significantly more in the modified fluid gelatin resuscitation group. In patients with traumatic or neurogenic shock due to acute volume deficiency, there was significantly better hemodynamic improvement, judged by CVP and PAOP measurements using the modified fluid gelatin for volume replacement than with lactated Ringer's solution during the first hour of resuscitation.

Epithelial maturation and extracellular matrix in reduced enamel epithelium.

OBJECTIVE: To evaluate epithelial-mesenchymal interactions in morphological homeostasis through histologically orientated observations on the reduced enamel in epithelium. STUDY DESIGN: Specimens were taken from impacted molar sites in 20 patients using the surgery. These were processed using standard histological, pathological and biochemical techniques. Slides were observed with a Nikon Eclipse E-600, Plan Apo piece, Microscopy, and photography was done using a Nikon Coolpix 990 digital camera. RESULTS: Radiolucent lesions displayed the supporting fibrous connective tissue wall with stratified squamous epithelium lining mostly. None of the specimens displayed prominent CAM 5.2, and anti-human K7 reacuvity, and PAS positive staining. CONCLUSION: While the results of this study suggest that the reduced enamel epithelium showed a lower tendency in cell cycle, it does indicate that a histologically oriented study of reduced enamel epithelium is needed for the understanding of epithelial-mesenchymal interactions in morphogenesis.

Lifetime environmental exposure to tobacco smoke and primary lung cancer of non-smoking Taiwanese women.

BACKGROUND: For a female population with a high lung cancer mortality rate, such as Taiwanese women, who smoke relatively rarely, but live in an environment with high male smoking prevalence, the risk and population burden of lung cancer due to environmental tobacco smoke (ETS) are relatively important. METHODS: An age-matched case-control study was designed to investigate the effects of cumulative environmental exposure to tobacco smoke during childhood and adult life on lung cancer risk among non-smoking women in Taiwan. Information on passive smoking from all possible sources and life periods were obtained from interviews with 268 and 445 lifetime non-smoking cases and controls. Conditional logistic regression and synergism 'S' index were applied to the data to assess the independent and joint effects of passive smoking in different life stages while controlling for possible confounding variables. RESULTS: Risks of contracting lung cancer among women near-distantly exposed to the highest level of ETS in childhood (>20 smoker-years) and in adult life (>40 smoker-years) were 1.8-fold (95% CI: 1.2-2.9) and 2.2-fold (95% CI: 1.4-3.7) higher than that among women being never exposed to ETS, and the two variables accounted for about 37% of tumours in this non-smoking female population. Children were found to be more susceptible to ETS than adults and such early exposure was found to modify the effect of subsequent tobacco smoke exposure in adult life based on an additive interaction model. CONCLUSIONS: Environmental tobacco smoke exposure occurring in childhood potentiates the effect of high doses of exposure in adult life in determining the development of lung cancer. Smoking prohibition would be expected to protect about 37% of non-smoking Taiwanese women against lung cancer.

Expression and regulation of macrophage inflammatory protein-2 gene by vanadium in mouse macrophages.

Environmental and occupational exposure to vanadium (V) dusts results in inflammation mainly confined to the respiratory tract. Macrophages apparently play an important role in mediating the inflammation via the production of many chemokines. In the current study, we investigated whether vanadium can regulate the gene expression of a CXC chemokine macrophage inflammatory protein-2 (MIP-2), and to determine the molecular mechanisms controlling MIP-2 gene expression. A mouse macrophage cell line RAW 264.7 was treated with sodium metavanadate (NaVO3) at the dose of 0.5, 5, or 10 microg/mi V. Northern blot analysis showed that induction of MIP-2 mRNA expression was in a dose-dependent manner. To define the time course of the inflammatory response, RAW 264.7 cells were exposed to 5 microg/ml V, MIP-2 mRNA in macrophages increased markedly as early as 1 h after treatment, maximally induced at 4 h and reduced to 2-fold above control levels by 6 and 8 h. The protein levels of MIP-2 in conditioned media, measured by enzyme-linked immunosorbent assay (ELISA), was well correlated with the levels of MIP-2 mRNA following all of the treatments in the study. In addition, the increase in MIP-2 mRNA expression by vanadium was attenuated by co-treatment with the antioxidant N-acetylcysteine (NAC), at the doses of 10 and 20 mM, suggesting that the induction of MIP-2 mRNA is mediated via the generation of reactive oxygen species (ROS). To further investigate transcriptional regulation of the MIP-2 gene expression by vanadium, we performed RNA decay assay by measuring the half-life of MIP-2 mRNA. Co-treatment of macrophages with the transcriptional inhibitor actinomycin D at 5 microg/ml following exposure to 5 microg/ml V for 4 h revealed complete stabilization of vanadium-induced MIP-2 mRNA and no sign of mRNA degradation, at least, for 6 h, in comparison to the half-life of MIP-2 mRNA was approximately 2.5 h by bacterial lipopolysaccharide (LPS) treatment, supporting post-transcriptional stabilization as the predominant role of MIP-2 gene expression. In conclusion, these observations demonstrate that in vitro vanadium can induce MIP-2 mRNA expression, mediating, at least in part, via the production of ROS. In addition, the increase in MIP-2 mRNA level involves, most likely, post-transcriptional control via increased mRNA stability.