Does ambient ozone air pollution trigger suicide attempts? A case cross-over analysis in Taipei.

Epidemiologic studies indicated that exposure to ambient air pollutants was associated with increased mortality rates attributed to suicide. The objective of this study was to investigate the potential relationship between ambient ozone (O3) levels and daily number of hospital admissions for suicide attempts in Taipei for the period 2008-2012 using a time-stratified case-crossover analysis. In the single-pollutant model (without adjustment for other pollutants), the risk of committing a suicide attempt increased by 9% on warm days and 27% on cool days for each interquartile range (IQR) rise in O3 levels, respectively. The concentration of O3 was thus significantly associated with daily number of suicide attempts both on warm and cool days. In the two-pollutant models, O3 levels remained significant after the inclusion of other air pollutants (particulate matter (PM10), PM2.5, sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO)) on cool days. However, on warm days, no significant correlation was found between O3 levels and reported daily number of suicide attempts. The relationship between O3 and suicide attempts appeared to be dependent upon temperature; however, the basis for these observations requires further investigation.

Bisphosphonate use and the risk of breast cancer: a meta-analysis of observational studies.

PURPOSE: To summarize current evidence of the association of bisphosphonate use with breast cancer risk, we used a systematic review and meta-analysis of observational studies to explore this issue. METHODS: A comprehensive search was conducted on PubMed, EMBASE, and the Cochrane Library. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random effects model. RESULTS: Bisphosphonate use was associated with a 16% lower breast cancer risk (pool RR0.84, 95%CI 0.77-0.90, n = 8). A protective effect of bisphosphonate was found in cohort studies (RR 0.85, 95%CI 0.80-0.90, n = 4) and case-control studies (RR 0.78, 95%CI 0.64-0.96, n = 4).We also found that the use of bisphosphonate resulted in a statistically significant reduction in all breast cancer risk (RR 0.87, 95%CI 0.81-0.93) and greater reduction in invasive breast cancer risk (RR 0.78, 95%CI 0.68-0.91) and contralateral breast cancer risk (RR, 0.41; 95% CI, 0.20-0.84).With respect to the type of bisphosphonate, we found that alendronate and etidronate resulted significant reduction in breast cancer risk. The short-term use of bisphosphonate (<1 y) led to nonsignificant change (RR 0.93, 95%CI 0.86-1.00), but a significant 26% reduction of breast cancer risk was noted with long-term use (>1 y) (RR 0.74, 95%CI 0.66-0.83). CONCLUSIONS: Our results supported bisphosphonate as being effective in preventing breast cancer, including invasive and contralateral breast cancer. Furthermore, the long-term use (>1 y) of bisphosphonate was more significant in lowering breast cancer risk.

Short-term effects of fine particulate air pollution on hospital admissions for hypertension: A time-stratified case-crossover study in Taipei.

This study was undertaken to determine whether there was a correlation between fine particle (PM2.5) levels and hospital admissions for hypertension in Taipei, Taiwan. Hospital admissions for hypertension and ambient air pollution data for Taipei were obtained for the period from 2009 to 2013. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single pollutant model (without adjustment for other pollutants), the risk of hospital admissions for hypertension was estimated to increase by 12% on warm days (>23°C) and 2% on cool days (<23°C), respectively. There was no indication of an association between levels of PM2.5 and risk of hospital admissions for hypertension. In two-pollutant model, PM2.5 remained nonsignificant after inclusion of any of the other air pollutants (SO2, NO2, CO, or O3) both on warm and cool days, but a numerically greater response was seen on warm days. Data thus indicate that in Taipei, hospital admissions for hypertension occur as a consequence of factors not related to ambient air exposure.

Short-term effects of ozone air pollution on hospital admissions for myocardial infarction: A time-stratified case-crossover study in Taipei.

This study was undertaken to determine whether there was a correlation between ambient ozone (O3) levels and number of hospital admissions for myocardial infarction (MI) in Taipei, Taiwan. Hospital admissions for MI and ambient air pollution data for Taipei were obtained for the period from 2006 to 2010. The relative risk (RR) of hospital admissions for MI was estimated using a time-stratified case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased RR for a number of MI admissions was significantly associated with higher O3 levels both on warm days (>23°C) and on cool days (<23°C). This observation was accompanied by an interquartile range elevation correlated with a 7% (95% CI = 2%-12%) and 17% (95% CI = 11%-25%) rise in number of MI admissions, respectively. In the two-pollutant models, no significant associations between ambient O3 concentrations and number of MI admissions were observed on warm days. However, on cool days, correlation between ambient O3 after inclusion of each of the other five pollutants, particulate matter (PM10 or PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2) or carbon monoxide (CO), and number of MI admissions remained significant. This study provides evidence that higher levels of ambient O3 increase the RR of number of hospital admissions for MI.

Aqueous Extracts of Toona sinensis Leaves Inhibit Renal Carcinoma Cell Growth and Migration Through JAK2/stat3, Akt, MEK/ERK, and mTOR/HIF-2α Pathways.

Toona sinensis (TS) is a type of deciduous tree, which is distributed widely in Asia and used as a traditional herb medicine. Previously, we demonstrated that aqueous extracts of TS leaves (TSL-1) induce apoptosis in two clear types of human renal carcinoma cells (ccRCC) via mitochondria-dependent pathway. In this study, we further investigated the more detailed mechanism of TSL-1-induced antitumor effects on ccRCCs. TSL-1 treatment arrested ccRCC cells in G0/G1 phase through the decrease of cyclin D1, cyclin-dependent kinase (CDK)2, and CDK4 as well as induction of p53 and FOXO3a protein expressions. On the other hand, the inhibitory effects of TSL-1 on migration were also observed in 786-O and A-498 cells. Mechanically, we presented that TSL-1 could suppress cell cycle progression and motility via inhibiting the phosphorylation of JAK2/stat3, Akt, MEK/ERK, and mTOR in a concentration- and time-dependent manner. Moreover, we found that TSL-1 inhibited p21, HIF-2α, c-Myc, VEGF, and MMP9 protein expressions in both cell lines. In conclusion, these findings suggested that TS-induced apoptosis and its antimigration activity in ccRCC cells were accompanied by inactivation of several oncogenic pathways.

Bisphosphonate use and the risk of endometrial cancer: a meta-analysis of observational studies.

BACKGROUND: The association of bisphosphonate use and the risk of endometrial cancer is still unclear. No meta-analysis was conducted to review the evidence concerning this topic. METHODS: Relevant studies were identified through PubMed and EMBASE and the Cochrane Library databases. The adjusted relative risk (RR) or odds ratios were determined using a fixed effects or random effects model, depending on the overall heterogeneity. RESULTS: Seven studies, including four cohort studies and three case-control studies, met the method criteria and were included. The random effects model showed a significant reduction in the risk association between bisphosphonate use and endometrial cancer incidence (RR 0.75, 95%CI 0.60-0.94, p = 0.064, I2 = 49.6%). A significantly protective effect was observed with the use of bisphosphonate for more than 1 year, and we found a statistically significant risk reduction with the use of bisphosphonate for more than 1 to 3 years (RR 0.58, 95%CI 0.47-0.72) and for more than 3 years (RR 0.44, 95%CI 0.28-0.70). However, with the use of bisphosphonate for less than 1 year (RR 0.92, 95%CI 0.64-1.34), we found no protective effect against endometrial cancer. CONCLUSIONS: We found that the use of bisphosphonate was significantly associated with a 25% risk reduction in the incidence of endometrial cancer in the overall analysis. Furthermore, the use of bisphosphonate for more than 1 year but not less than 1 year may have a more beneficial effect on endometrial cancer risk. Copyright © 2016 John Wiley & Sons, Ltd.

Air pollution exposure and daily clinical visits for allergic rhinitis in a subtropical city: Taipei, Taiwan.

This study was undertaken to determine whether there was an association between air pollutant level exposure and daily clinic visits for allergic rhinitis (AR) in Taipei, Taiwan. Daily clinic visits for AR and ambient air pollution data for Taipei were obtained for the period of 2006-2011. The relative risk for clinic visits for AR was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single-pollutant models, on warm days (>23ºC) significant positive associations were found for increased rate of AR occurrence and ambient levels of particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). On cool days (<23ºC), all air pollutants were significantly associated with elevated number of AR visits except SO2. For the two-pollutant models, PM10, O3, and NO2 were significantly associated with higher rate of AR visits in combination with each of the other four pollutants on cool days. On warm days, CO levels remained significantly related with increased AR visits in all two-pollutant models. This study provides evidence that higher levels of ambient air contaminants enhance the risk of elevated frequency of clinic visits for AR.

Engineered xylose utilization enhances bio-products productivity in the cyanobacterium Synechocystis sp. PCC 6803.

Hydrolysis of plant biomass generates a mixture of simple sugars that is particularly rich in glucose and xylose. Fermentation of the released sugars emits CO2 as byproduct due to metabolic inefficiencies. Therefore, the ability of a microbe to simultaneously convert biomass sugars and photosynthetically fix CO2 into target products is very desirable. In this work, the cyanobacterium, Synechocystis 6803, was engineered to grow on xylose in addition to glucose. Both the xylA (xylose isomerase) and xylB (xylulokinase) genes from Escherichia coli were required to confer xylose utilization, but a xylose-specific transporter was not required. Introduction of xylAB into an ethylene-producing strain increased the rate of ethylene production in the presence of xylose. Additionally, introduction of xylAB into a glycogen-synthesis mutant enhanced production of keto acids. Isotopic tracer studies found that nearly half of the carbon in the excreted keto acids was derived from the engineered xylose metabolism, while the remainder was derived from CO2 fixation.

Air pollution and daily clinic visits for migraine in a subtropical city: Taipei, Taiwan.

This study was undertaken to determine whether there was an association between air pollutant levels and daily clinic visits for migraine in Taipei, Taiwan. Daily clinic visits for migraine and ambient air pollution data for Taipei were obtained for the period 2006-2011. The relative risk of clinic visits for migraine was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single-pollutant models, on warm days (>23°C) statistically significant positive associations were found for increased rate of migraine occurrence and levels of particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). On cool days (<23°C), all pollutants were significantly associated with increased migraine visits except CO and SO2. For the two-pollutant models, O3 and NO2 were significant for higher rate of migraine visits in combination with each of the other four pollutants on cool days. On warm days, CO remained statistically significant in all two-pollutant models. This study provides evidence that higher levels of ambient air pollutants enhance the risk of clinic visits for migraine.

Fine particulate air pollution and outpatient department visits for headache in Taipei, Taiwan.

This study was undertaken to determine whether there was an association between fine particle matter (PM(2.5)) levels and daily outpatient department visits (OPD) for headaches in Taipei, Taiwan. Daily OPD visits for headaches and ambient air pollution data for Taipei were obtained for the period 2006-2011. The relative risk of visits for OPD headaches was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased OPD visits for headaches were significantly associated with levels of PM(2.5) both on warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 12% (95% CI = 10-14%) and 3% (95% CI = 1-5%) elevation in OPD visits for headaches, respectively. In the two-pollutant models, PM(2.5) remained significant after inclusion of sulfur dioxide (SO2) or ozone (O3) on both warm and cool days. This study provides evidence that higher levels of PM(2.5) increase the risk of OPD visits for headaches in Taipei, Taiwan.

Relationship between hemorrhagic stroke hospitalization and exposure to fine particulate air pollution in Taipei, Taiwan.

This study was undertaken to determine whether there was a correlation between fine particle (PM2.5) levels and hospital admissions for hemorrhagic stroke (HS) in Taipei, Taiwan. Hospital admissions for HS and ambient air pollution data for Taipei were obtained for the period 2006-2010. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased HS admissions were significantly associated with PM2.5 levels both on warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 12% (95% CI = 7-18%) and 4% (95% CI = 0-8%) elevation in admissions for HS, respectively. In the two-pollutant models, PM2.5 remained significantly high after inclusion of SO2 or O3 on both warm and cool days. This study provides evidence that higher levels of PM2.5 increase the risk of hospital admissions for HS.

Fine particulate air pollution and hospital admissions for asthma: a case-crossover study in Taipei.

This study was undertaken to determine whether there was a correlation between fine particles (PM2.5) levels and hospital admissions for asthma in Taipei, Taiwan. Hospital admissions for asthma and ambient air pollution data for Taipei were obtained for the period of 2006-2010. The relative risk of hospital admissions for asthma was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased asthma admissions were significantly associated with PM2.5 levels both on warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 12% (95% CI = 6-18%) and 3% (95% CI = 0-8%) elevation in admissions for asthma, respectively. In the two-pollutant models, PM2.5 levels remained significant for increased asthma admissions after inclusion of SO2 or O3 both on warm and cool days. This study provides evidence that higher levels of PM2.5 elevate the risk of hospital admissions for asthma in Taiwan.

Short-term effects of fine particulate air pollution on hospital admissions for respiratory diseases: a case-crossover study in a tropical city.

This study was undertaken to determine whether there was a correlation between fine particles (PM2.5) levels and hospital admissions for respiratory diseases in Kaohsiung, Taiwan. Hospital admissions for respiratory diseases including pneumonia, asthma, and chronic obstructive pulmonary disease (COPD) and ambient air pollution data for Kaohsiung were obtained for the period 2006-2010. The relative risk (RR) of hospital admissions for respiratory diseases was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and chronic time trends. For the single-pollutant model (without adjustment for other pollutants), increased number of admissions for respiratory diseases were significantly associated with higher PM2.5 levels only on cool days (<25°C), with an interquartile range rise associated with a 50 (95% CI% = 45-55%), 40% (95% CI = 25-58%), and 46% (95% CI = 36-57%) elevation in frequency of admissions for pneumonia, asthma, and COPD, respectively. In the two-pollutant models, PM2.5 levels remained significant even controlling for sulfur dioxide, nitrogen dioxide, carbon monoxide, or ozone on cool days. This study provides evidence that higher levels of PM2.5 increase the risk of hospital admissions for respiratory diseases in Taiwan.

Parity, age at first birth and risk of death from kidney cancer: a population-based cohort study in Taiwan.

BACKGROUND: This study was undertaken to examine whether there is an association between parity and age at first birth and risk of kidney cancer. METHODS: The study cohort consisted of 1 292 462 women who had a first and singleton childbirth between 1 January 1978 and 31 December 1987. We tracked each woman from the time of her first childbirth to 31 December 2009, and their vital status was ascertained by linking records with the computerized mortality database. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of death from kidney cancer associated with parity and age at first birth. RESULTS: There were 95 kidney cancer deaths during 34,980,246 person-years of follow-up. The mortality rate of kidney cancer was 0.27 cases per 100,000 person-years. The adjusted HR was 1.88 [95% confidence interval (CI) 1.10-3.19] for women who gave birth between 24 and 26 years of age and 2.52 (95% CI 1.44-4.40) for women who gave birth after 26 years of age, when compared with women who gave birth when <23 years of age. A trend of increasing risk of kidney cancer was seen with increasing age at first birth. The adjusted HR was 0.88 (95% CI 0.49-1.59) for women who had two children and 0.89 (95% CI 0.47-1.67) for women with three or more births, when compared with women who had given birth to only one child. CONCLUSION: This study is the first to suggest that early age at first birth may confer a protective effect on the risk of kidney cancer.

Herpes zoster and subsequent risk of cancer: a population-based study.

BACKGROUND: In this cohort study, we investigated whether a diagnosis of herpes zoster (HZ) was associated with a higher risk of subsequent cancer as compared with the Taiwanese general population. METHODS: Data were obtained from the Taiwan National Health Insurance Research Database. In total, 38 743 patients who were aged 50 years or older and had received ambulatory care for HZ between 1997 and 2006 were identified as the study cohort; 116 229 age- and sex-matched patients without HZ were included as the comparison cohort. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) for subsequent cancer, after controlling for potential confounders. RESULTS: The HR for subsequent cancer varied according to time since HZ diagnosis. The HR was 1.58 (95% CI, 1.38-1.80) within the first year, 1.30 (95% CI, 1.15-1.46) between 1 and 2 years, 1.10 (95% CI, 0.98-1.24) between 2 and 3 years, 1.02 (95% CI, 0.91-1.15) between 3 and 4 years, and 1.08 (95% CI, 0.96-1.21) between 4 and 5 years. The risk of subsequent cancer, particularly lung cancer, was significantly higher during the first 2 years after initial diagnosis of HZ. CONCLUSIONS: Our findings suggest that an HZ diagnosis is a marker of occult malignancy, particularly in lung cancer. The HRs for cancer decreased gradually over time and were no longer significant after 2 years of follow-up, which indicates that the association between HZ and cancer is likely due to detection bias.

Short-term effects of fine particulate air pollution on ischemic stroke occurrence: a case-crossover study.

This study was undertaken to determine whether there was a correlation between fine particles (PM2.5) levels and hospital admissions for ischemic stroke (IS) in Taipei, Taiwan. Hospital admissions for IS and ambient air pollution data for Taipei were obtained for the period from 2006-2010. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased admissions for IS were significantly associated with higher levels of PM2.5 on both warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 11% (95% CI = 8-14%) and 4% (95% CI = 2-7%) elevation in admissions for IS, respectively. In the two-pollutant models, PM2.5 remained significantly increased after inclusion of sulfur dioxide (SO2) or ozone (O3) on both warm and cool days. This study provides evidence that higher levels of PM2.5 enhance the risk of hospital admissions for IS.

Trihalomethanes in drinking water and the risk of death from esophageal cancer: does hardness in drinking water matter?

The objectives of this study were to (1) examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of esophageal cancer occurrence and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water modify the effects of TTHM on risk to develop esophageal cancer. A matched case-control study was used to investigate the relationship between the risk of death attributed to esophageal cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All esophageal cancer deaths in the 53 municipalities from 2006 through 2010 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from Taiwan Environmental Protection Administration. Information on the levels of Ca and Mg in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM, Ca, and Mg exposure via drinking water. Relative to individuals whose TTHM exposure level <4.9 ppb, the adjusted odds ratio (OR) with 95% confidence interval (CI) for esophageal cancer was 1.02 (0.84-1.23) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. There was evidence of an interaction between drinking-water TTHM levels and low Ca and Mg intake. Our findings showed that the correlation between TTHM exposure and risk of esophageal cancer development was influenced by Ca and Mg levels in drinking water. This is the first study to report effect modification by Ca and Mg intake from drinking water on the correlation between TTHM exposure and risk of esophageal cancer occurrence. Increased knowledge of the interaction between Ca, Mg, and TTHM in reducing risk of esophageal cancer development will aid in public policymaking and standard setting for drinking water.

Magnesium in drinking water modifies the association between nitrate ingestion and risk of death from esophageal cancer.

The objective of this study was to explore whether magnesium (Mg) levels in drinking water modified the effects of nitrate on esophageal cancer risk occurrence. A matched cancer case-control study was used to investigate the relationship between the risk of death from esophageal cancer and exposure to nitrate in drinking water in Taiwan. All esophageal cancer deaths of Taiwan residents from 2006 through 2010 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO(3)-N) and Mg in drinking water were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO(3)-N and Mg exposure via drinking water. Evidence of an interaction was noted between drinking water NO(3)-N and Mg intake. This is the first study to report effect modification by Mg intake originating from drinking water on an association between NO(3)-N exposure and increased risk mortality attributed to esophageal cancer.

Short-term effects of fine particulate air pollution on emergency room visits for cardiac arrhythmias: a case-crossover study in Taipei.

This study was undertaken to determine whether there was an association between fine particles (PM2.5) levels and number of emergency room (ER) visits for cardiac arrhythmias in Taipei, Taiwan. ER visits for cardiac arrhythmias and ambient air pollution data for Taipei were obtained for the period 2006-2010. The relative risk (RR) of ER visits was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased numbers of ER cardiac arrhythmia visits were significantly associated with PM2.5 on both warm days (>23°C) and cool days (< 23°C), with an interquartile range rise associated with a 10% (95% CI = -15%) and 4% (95% CI = 0-8%) elevation in number of ER visits for cardiac arrhythmias, respectively. In the two-pollutant models, PM2.5 levels remained significant after inclusion of sulfur dioxide (SO2) or ozone (O3) on both warm and cool days. This study provides evidence that higher levels of PM2.5 increase the risk of number of ER visits for cardiac arrhythmias.

Activation of HGF/c-Met signaling by ultrafine carbon particles and its contribution to alveolar type II cell proliferation.

Hepatocyte growth factor (HGF) is a potent mitogen and motogen for various epithelial cells. The present study aimed to explore the role of HGF and c-Met receptor in ultrafine carbon particle-induced alveolar type II epithelial (type II) cell proliferation. ICR mice were intratracheally instilled with 100 µg ultrafine carbon black (ufCB) and killed at 21, 48, and 72 days postexposure to examine type II cell proliferation, HGF release, and c-Met activation. In vivo and in vitro applications of neutralizing anti-HGF antibody were used to investigate the causal role of HGF in cell proliferation. The Met kinase inhibitor SU11274 and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 were used to delineate the involvement of c-Met/ERK1/2 in rat L2 pulmonary epithelial cell proliferation. The results demonstrated that in vivo exposure to 100 µg ufCB caused increased HGF in bronchoalveolar lavage fluid, as well as increased HGF production, c-Met phosphorylation, and cell proliferation in type II cells. In vitro study revealed that ufCB caused a dose-dependent increase in HGF release, c-Met phosphorylation, and cell proliferation. Importantly, treatment with the neutralizing anti-HGF antibody significantly blocked ufCB-induced in vivo and in vitro type II cell proliferation. Moreover, SU11274 and PD98059 significantly reduced ufCB-increased L2 cell proliferation. Results from Western blotting demonstrated that SU11274 successfully suppressed ufCB-induced phosphorylation of c-Met and ERK1/2. In summary, the activation of HGF/c-Met signaling is a major pathway involved in ufCB-induced type II cell proliferation.