Tumor M2-PK: A novel urine marker of bladder cancer.

PURPOSE: Bladder cancer is a "Warburg-like" tumor characterized by a reliance on aerobic glycolysis and expression of pyruvate kinase M2 (PKM2). PKM2 oscillates between an active tetramer and an inactive dimer. We aim to further characterize PKM2, in particular PKM2 dimer, as a urinary biomarker of bladder cancer and a potential target for treatment. METHODS: HTB-9, HTB-5, and UM-UC3 bladder cancer cells were assessed for proliferation under differential glucose levels using the hexosaminidase assay. Western blot and Blue-native analysis was performed for protein expression of PKM2. Shikonin, an herb that is known to bind and inhibit PKM2, was utilized to determine if PKM2 has a role in glucose usage and cellular proliferation in bladder cancer cells by caspase activity assay. Institutional review board approval was obtained to collect healthy control and bladder cancer patient urine samples. The ScheBo M2-PK EDTA Plasma Test was performed on urine samples to assess urine Tumor M2-PK values. RESULTS: The three bladder cancer cell lines tested all demonstrate statistically significant increases in proliferation when exposed to higher level of glucose (200mg/dL). Similarly, low doses of glucose (25mg/dL) result in reduced proliferation. Increased cell growth in higher glucose concentration correlated with up-regulation of PKM2 protein expression. Shikonin, a PKM2 inhibitor, reduced cell proliferation and switched PKM2 isoforms from the dimer to tetramer. Lastly, dimer PKM2 (Tumor-M2PK) levels were assessed in the urine samples from bladder cancer (Bca) patients and healthy controls. Tumor M2-PK significantly correlated with the presence of BCa in our subjects. CONCLUSIONS: Our studies demonstrate the potential of PKM2, specifically the dimer (Tumor-M2PK) as a target of drug therapy and as a urinary marker for bladder cancer.

The relationship between iodine nutrition and thyroid disease in lactating women with different iodine intakes.

Areas with low, adequate and excessive I content in water co-exist in China. Limited data are currently available on I nutrition and thyroid disease in lactating women and their breast-fed infants with different I intakes. This study aimed to evaluate I nutrition in both lactating women and their infants and the prevalence of thyroid disease in areas with different levels of I in water. From January to June 2014, a total of 343 healthy lactating women (excluding those taking anti-thyroid drugs or I supplements within a year of the study, consuming seafood at the time of the study or those diagnosed with congenital thyroid disease) from Beihai in Guangxi province and Jiajiazhuang, Yangcheng, Jicun and Pingyao townships in Shanxi province were selected. Compared with the I-sufficient group, median urinary I concentrations in both lactating women and infants as well as breast milk I levels were significantly lower in the I-deficient group (P<0·001). The prevalence of thyroid disease in lactating women, particularly subclinical hypothyroidism, was higher in the I-excess group than in the I-sufficient group (P<0·05). In areas with excessive water I content, high thyroid peroxidase antibody and high thyroglobulin levels were risk factors for abnormal thyroid-stimulating hormone levels. Our data collectively suggest that excessive I intake potentially causes subclinical hypothyroidism in lactating women. Moreover, enhanced monitoring of I status is important to avoid adverse effects of I deficiency or excess, particularly in susceptible populations such as pregnant or lactating women and infants.

Neonatal thyroid status in an area of iodine sufficiency.

BACKGROUND: Iodine deficiency constitutes a public health problem in many countries worldwide. Fetal neurodevelopment is affected by maternal iodine intake. The aim of present study was to assess urinary iodine excretion (UIE) in the 3 trimesters of pregnancy and evaluate its association with newborn thyroid function in Tehran, an area of iodine sufficiency. METHODS: Based on median urinary iodine in 3 trimesters, 138 pregnant women were divided into 2 groups with UIE<150 (group I) and UIE ≥ 150 µg/l (group II). Cord blood samples of their newborns were evaluated for serum concentrations of TSH, T3, T4, free T4 (FT4), and thyroglobolin. Quartiles of UIE were also determined. Correlations between mothers' UIE and newborns' thyroid function in both groups were investigated. RESULTS: Fifty-two pregnant women (38%) had median UIE<150 µg/l and 86 had (62%) UIE ≥ 150 µg/l. Median UIE in groups I and II in the 1st, 2nd, and 3rd trimesters were 125 and 212 µg/l, 97 and 213 µg/l, 93 and 227 µg/l, respectively. No significant difference was seen in thyroid function of newborns in the 2 groups. Mean concentrations of T4, T3, FT4, and TSH of newborn did not show significant difference in median UIE of mothers in various quartiles. CONCLUSION: This study shows that newborns, irrespective of mothers' UIE, in an area with a sustained iodine supplementation program, may not be at risk of alterations in thyroid functions.

Selenium status and cardiovascular risk profile in healthy adult Saudi males.

The purpose of this research was to investigate the relationship between selenium levels, thyroid function and other coronary risk factors in 140 Saudi subjects without overt coronary heart disease stratified by age. Demographic data and serum fasting lipid profile, glucose, thyroid function tests, selenium status and dietary intake was assessed. The relationships between selenium status, thyroid function and cardiovascular risk factors were assessed by univariate and multivariate analysis. The results showed that thyroid hormone levels did not differ with age. Erythrocyte glutathione peroxidase (GPx) levels were significantly higher in the youngest vs. oldest tertile (p<0.0001). Selenium and iodine intake did not differ significantly with age tertile, but the average intake for the population sample was below the estimated average requirements for both elements. Serum lipoprotein (a) concentrations correlated with selenium (r = 0.417, p<0.0001) and TSH (r = 0.172, p<0.05). After adjustment for confounding variables; serum fT(4) and erythrocytes GPx remained significant determinants of serum TSH levels, whilst serum selenium and TSH were determinants of serum fT(4) levels. Serum Lp(a), a coronary risk factor, was strongly related to measures of selenium status. A significant relationship between measures of selenium status and thyroid function was found. Serum Lp(a) a known risk factor for cardiovascular disease was also related to selenium status in our population.

The use of sugar as a vehicle for iodine fortification in endemic iodine deficiency.

The use of sugar as a vehicle for iodine supplementation was explored in a study of iodine deficiency in the Sudan. A survey of sugar consumption was conducted and established a widespread and uniform intake of sugar in all ages with no differences among socio-economic groups. The daily intake among adults varied from 48 g to 78 g as examined in five different geographical areas in the country. Iodinated sugar was produced by addition to sugar solution prior to crystallisation in an evapocrystallizer or sprayed on the conveyor of cured sugar before it entered the dryers. Subsequently, the iodinated sugar was given to members of 18 and 60 families in a mildly (urinary iodine < 5.1 micrograms/dl) and moderately (urinary iodine < 3 micrograms/dl) iodine deficient areas, respectively, over a 1-month and a 6-month period, respectively. In both tests, improvements were recorded, i.e. the rates of goitre decreased, urinary iodine levels increased significantly (from 5.1 to 14.4 micrograms/dl and from 3 to 9.8 micrograms/dl, respectively) and thyroid hormones values rose. No side effects were noted. The results indicate that fortification of sugar with iodine may serve as a new alternative approach in attempts to eradicate iodine deficiency related disorders in endemic areas.