Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TAM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
PubMed2005

In vitro and in vivo effects of combination of Trastuzumab (Herceptin) and Tamoxifen in breast cancer.

Extensive interactions between estrogen receptor alpha (ERalpha) and HER2 signaling pathways have been described. Using BT-474 human breast cancer cells, we have previously shown that the combination of tamoxifen (TAM) and Herceptin results in strong synergistic growth inhibition, enhancement of G(0)-G(1) cell cycle accumulation, inhibition of HER2 activity and a cytostatic effect without cell death. To further examine the underlying mechanism of synergy, we investigated the effect of this drug combination on ERalpha function and growth factor downstream signaling. TAM caused a small increase in ERalpha levels while Herceptin had no effect, and both drugs caused an increase in the level of Ser118-phosphorylated ERalpha. However, both TAM and Herceptin individually inhibited ERalpha transcriptional activity, although the combination did not have a greater effect than either single agent. Herceptin inhibited MAPK and Akt activity, while TAM had no effect on these either as a single agent or when added to Herceptin. Using a BALB/c athymic BT-474 in vivo xenograft model, the drug combination (Herceptin 0.3 mg/kg i.p. twice weekly, TAM 1.0 mg/mouse i.p. three times per week) showed a greater inhibition of tumor growth compared to either single agent. Tumor extracts and fixed sections were examined at the end of the treatment period for treatment-specific alterations: we noted a paradoxical proliferation-inducing effect of TAM that was reversed by the addition of Herceptin. Our results indicate that combined targeting of both peptide growth factor receptors and ERalpha represents a promising breast cancer treatment strategy.

Animals↗
PubMed2006

Pharmacoeconomic analysis of adjuvant therapy with exemestane, anastrozole, letrozole or tamoxifen in postmenopausal women with operable and estrogen receptor-positive breast cancer.

OBJECTIVE: To compare the efficiency of adjuvant therapy with aromatase inhibitors or with tamoxifen in postmenopausal women with operable breast cancer and positive estrogen receptors. MATERIAL AND METHODS: A cost-utility analysis was performed based on a Markov model, from the Spanish National Health Care System perspective, comparing the treatment with exemestane (EXE: 25 mg/day) or tamoxifen (TAM: 20 mg/day) after 2-3 years of monotherapy with TAM; anastrozole (ANA, 1 mg/day) or TAM (20 mg/day) without previous TAM therapy; and letrozole (LET: 2.5 mg/day) or placebo after 5 years of monotherapy with TAM. The follow-up of a hypothetical cohort of women starting treatment at 63 years of age was simulated during 10 and 20 years. The probabilities of transition between health states and quality adjusted life years (QALYs) were obtained from the literature, and the unit costs (euro corresponding to 2004) from a Spanish database. RESULTS: After 10 and 20 years of follow-up, more QALYs per patient would be gained with the EXE scheme (0.230-0.286 and 0.566-0.708, respectively) than with ANA (0.114 and 0.285) and LET (0.176 and 0.474). The cost of gaining one QALY was lower with the EXE scheme (50,801-62,522 euro and 28,849- 35,371 euro, respectively) than with ANA (104,272 euro and 62,477 euro) and LET (91,210 euro and 49,460 euro). The result was stable for the cost per life-year gained (LYG) and in the sensitivity analysis. CONCLUSIONS: The EXE scheme after TAM is more cost-effective than the ANA and LET schemes.

Anastrozole↗
PubMed1995

Tamoxifen and its active metabolite inhibit growth of estrogen receptor-negative MDA-MB-435 cells.

Tamoxifen (TAM), the non-steroidal anti-estrogen most widely administered to breast cancer patients, acts, at least in part, by competing with estrogen receptors (ER). However, the existence of an alternative mechanism of action for this drug is supported by the clinical observations that: (a) 30% of patients with ER-negative cancer cells respond to TAM, and (b) 30% of patients with ER-positive cancer cells are not sensitive to this anti-estrogen. In this study, we observed that growth of the human ER-negative breast cancer cell line MDA-MB-435 was inhibited by TAM and 4-hydroxytamoxifen (4OH-TAM) in a concentration-dependent fashion. Both monoclonal enzymoimmunoassay and Dextran Charcoal Coated Scatchard radioimmunoassay analysis demonstrated that this MDA-MB-435 cell line does not express ER. The absence of ER in MDA-MB-435 cells was also demonstrated at the mRNA level by both northern blot hybridization and reverse transcription-polymerase chain reaction techniques. MDA-MB-435 cell proliferation was not affected by 17 beta-estradiol or by the pure anti-estrogen ICI 164384, further demonstrating that the observed effects of TAM and its active metabolite on the proliferation of MDA-MB-435 cells were due to an ER-independent mechanism, yet to be identified. MDA-MB-435 thus appears to be a promising original model for the study of the alternative ER-independent mechanisms of action of TAM.

Breast Neoplasms↗
PubMed1994

Tamoxifen and hydroxytamoxifen as intramembraneous inhibitors of lipid peroxidation. Evidence for peroxyl radical scavenging activity.

Tamoxifen (TAM) is the antiestrogen most widely used in the chemotherapy and chemoprevention of breast cancer. It has been reported that TAM and its more active metabolite 4-hydroxytamoxifen (OHTAM) induce multiple cellular effects, including antioxidant actions. Here sarcoplasmic reticulum membranes (SR) were used as a simple model of oxidation to clarify the antioxidant action type and mechanisms of these anticancer drugs on lipid peroxidation induced by Fe2+/ascorbate and peroxyl radicals generated by the water-soluble 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) and by the lipid-soluble 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN). Peroxidation was monitored by different assay systems, namely cis-parinaric acid (PnA) fluorescence quenching, production of thiobarbituric acid-reactive substances, polyunsaturated fatty acids (PUFA) degradation and oxygen consumption. TAM and OHTAM are efficient inhibitors of lipid peroxidation induced by Fe2+/ascorbate and strong intramembraneous scavengers of peroxyl radicals generated either in the water or lipid phases by AAPH and AMVN, respectively. However, these drugs are not typical chain-breaking antioxidant compounds as compared with vitamin E. Additionally, their antioxidant effectiveness enhances the protective capacity of vitamin E against lipid peroxidation induced by AMVN. OHTAM is a more powerful intramembraneous inhibitor of lipid peroxidation as compared with TAM; this effectiveness not correlating with alterations on membrane fluidity may be due to the presence of a hydrogen-donating HO-group in the OHTAM molecule and its preferential location in the outer bilayer regions where it can donate the hydrogen atom to quench free radicals capable of initiating the membrane oxidative degradation. The stronger OHTAM intramembraneous scavenger capacity over TAM also correlates with its higher partition in biomembranes. Therefore, the strong peroxyl radical scavenger activity of OHTAM in the hydrophobic membrane phase may putatively contribute to the mechanisms of cytostatic and chemopreventive action of its promoter TAM on development of breast cancer.

Amidines↗
PubMed1994

Tamoxifen stimulates phospholipase D activity by an estrogen receptor-independent mechanism.

The effects of tamoxifen (TAM), a widely used agent in the treatment of breast cancer, were examined on phospholipase D (PLD)-mediated phospholipid hydrolysis. In drug-sensitive MCF-7 human breast carcinoma cells TAM, similar to several well-established activators of PLD, had no effect on phospholipid hydrolysis. In an estrogen receptor-deficient multidrug-resistant subline of MCF-7 cells, TAM preferentially stimulated the hydrolysis of phosphatidylethanolamine; two-fold stimulation required 2.5 or 5 microM TAM in the absence or presence of serum, respectively. In NIH 3T3 fibroblasts significant (4- to 4.8-fold) stimulation of phosphatidylethanolamine and phosphatidylcholine hydrolysis in the presence of serum required 10 microM TAM. These data establish that TAM can stimulate PLD activity by an estrogen receptor-independent mechanism.

3T3 Cells↗
PubMed1990

Blockade of lordosis by androst-1,4,6-triene-3,17-dione (ATD) and tamoxifen in female hamsters primed with testosterone propionate.

Normal female hamsters display lordosis after testosterone propionate (TP) plus progesterone (P) treatments. Such effect is probably mediated through aromatization of testosterone (T) into estradiol. If so, then an aromatase inhibitor (ATD) or an estrogen antagonist (tamoxifen, TAM) should be able to block the activational effect of T on lordosis. To test this hypothesis, 48 ovariectomized female hamsters were assigned into six groups which, according to treatments received, were ATD + TP, TAM + TP, OIL + TP, ATD + EB (estradiol benzoate), TAM + EB, and OIL + EB groups. The groups received assigned treatments for 2 days and were injected with P on the third day. Five minutes of behavior test was conducted 4 hr after P injection. The OIL + TP, OIL + EB, and ATD + EB groups all had averaged total lordosis duration (TLD) longer than 200 sec. The TLD of the TAM + EB group was only 117 sec. The ATD + TP and TAM + TP groups showed almost no lordosis. The results showed that the estrogen antagonist (TAM) impaired lordosis no matter whether the animals were primed with TP or EB, but the aromatase inhibitor (ATD) blocked lordosis only in TP primed females. It is concluded that the aromatization of T to estrogen is required for testosterone activation of lordosis in female hamsters.

Androstatrienes↗
PubMed1990

In vitro and in vivo binding of toremifene and its metabolites in rat uterus.

The in vitro binding affinities of toremifene (TOR), 4-hydroxy toremifene (4-OH-TOR) and several other metabolites for the rat uterine cytosolic estrogen receptor were compared with those of tamoxifen (TAM) and 4-hydroxy tamoxifen (4-OH-TAM). Only small differences were observed and the binding affinities of both 4-hydroxy metabolites were similar to that of estradiol (E2). Uterine uptake and subcellular distribution of [3H]TOR and [3H]TAM were then compared at 1, 8 and 72 h after administration to castrated rats. The uptake and retention of both antiestrogens were similar at all times. In each case the amount of nuclear bound radioactivity declined to low levels at 8 and 72 h but the ratios of 4-OH-TAM/TAM and 4-OH-TOR/TOR determined by HPLC analysis increased dramatically at 72 h. The level of radioactivity in both plasma and uterine cytosol at 72 h was significantly higher following [3H]TAM administration. However, most of the radioactivity appeared to be in a conjugated form since it was not extractable with solvent. Finally, the ability of prior administration of each antiestrogen (100 mg/kg) to block uterine [3H]estradiol uptake was examined at 3 and 7 days. It was found that uterine wet weights were higher than control one week after administration of both compounds. Prior administration of TOR increased nuclear uptake of [3H]E2 whereas TAM had no effect. The results of these experiments suggest that toremifene and tamoxifen have very similar in vitro and in vivo binding properties but differences in metabolism exist that may be important.

Animals↗
PubMed1990

Establishment and characterization of UM-EC-2, a tamoxifen-sensitive, estrogen receptor-negative human endometrial carcinoma cell line.

UM-EC-2 was established from a patient with poorly differentiated stage IB endometrial carcinoma. This cell line produces tumors in nude mice that have the same histological features as the patient's tumor. UM-EC-2 cells express b2-microglobulin, the epidermal growth factor receptor (EGF), and the H blood group antigen. This membrane antigen phenotype is consistent with cells of human endometrial origin. The karyotype of UM-EC-2 is fairly complex, with rearrangements affecting all chromosomes except 3, 10, 14, 19, and 20. There were two populations of cells, a hyperdiploid population with a modal number of 53-55 and a hypertetraploid population with a modal number of 109. A postulated sequence of events before and after tetraploidization is suggested based on the number of copies of individual chromosomes and rearrangements. Comparison of the UM-EC-2 karyotype to that of UM-EC-1 (a previously described line from a different patient with endometrial carcinoma) revealed that the two lines share eight very similar chromosome changes, which include loss of most of chromosome 4, breakpoints affecting proximal bands on 8p, loss of most of 9q, a breakpoint at 12q22, loss of 13q, breakpoints in proximal bands on 18q, and a breakpoint at 22p11. These changes may represent nonrandom chromosome abnormalities in poorly differentiated endometrial cancer. Estrogen (ER) and progesterone (PgR) receptors were not detected in either the primary tumor or the cell line. Nevertheless, UM-EC-2 cells were very sensitive to growth inhibition by tamoxifen (TAM) in vitro. One micromolar TAM caused 50% inhibition of cell growth, 2.5 microM caused cytostasis, and 5 microM TAM was cytotoxic, killing all cells after 5-7 days of exposure to the drug. Paradoxically, 100 nM estradiol (E2) caused a moderate increase in the growth of the cells but it did not prevent or reverse growth inhibitory effects of TAM. These findings support the concept that in some tumors TAM causes growth inhibition by an ER-independent mechanism. UM-EC-2 cells were also sensitive to growth regulation by EGF. Thus, these cells provide a new in vitro model of human endometrial cancer in which the roles of both TAM and EGF as growth regulatory substances can be investigated.

Antigens, Neoplasm↗
PubMed1989

Differential responses of pituitary kallikrein and prolactin to tamoxifen and chlorotrianisene.

Glandular kallikrein, a trypsin-like serine protease, and prolactin (PRL) are both estrogen-induced proteins in rat anterior pituitary lactotrophs. The estrogen agonist and antagonist effects of tamoxifen (TAM, a triphenylethylene antiestrogen) and chlorotrianisene (TACE, a triphenylethylene estrogen) on anterior pituitary glandular kallikrein and PRL were examined to see if TAM and TACE differentially affect these estrogen response of lactotrophs after in vivo dosing of rats. TAM and TACE acted as partial agonists on PRL and uterine weight induction. In contrast, on glandular kallikrein induction TAM acted as a pure estrogen antagonist and TACE acted as an almost pure antagonist. The results document that both TAM and TACE exhibit protein-specific estrogen agonist and antagonist efficacies in lactotrophs, with the estrogen induction of glandular kallikrein being particularly sensitive to antagonism by TAM in vivo. The marked antiestrogen character of TACE was surprising since TACE has been classified and clinically used as an estrogen.

Animals↗
PubMed1993

Chemopreventive effects of tamoxifen in ethyl methanesulphonate-induced rat mammary carcinogenesis.

Ethyl methanesulphonate (EMS), an alkylating agent and a potent mutagen, has been shown to be an effective carcinogen for the induction of mammary carcinoma in female Wistar King A rats. We therefore utilized this new system to assess the effects of tamoxifen (TAM) on mammary carcinogenesis. In Group A rats, given EMS orally for a period of 12 weeks, mammary carcinomas were first detected at the 13th week and were found in all surviving rats at the 20th week. The concomitant administration of TAM for 4 weeks, in Group B rats, retarded the development of the tumors significantly. There was a significant reduction in the incidence of estrogen receptor (ER)-positive tumors in the rats previously exposed to TAM; 100% in Group A versus 50% in Group B. Neither the progesterone receptor (PgR) nor androgen receptor (AR) status of the tumors were significantly different between these two groups. The inhibitory effects of TAM on tumor induction was also observed when TAM treatment started after EMS administration, though the intensity was smaller than that in Group B. These findings suggest the preventive action of TAM on EMS-induced mammary carcinogenesis, and indicate that this tumor system may provide a feasible model for research on chemoprevention and hormone therapy using an antiestrogen for human mammary carcinoma.

Animals↗
PubMed1990

Tamoxifen blocks both proliferation and voltage-dependent K+ channels of neuroblastoma cells.

The effects of tamoxifen (TAM) on cell proliferation and voltage-dependent K+ channels were studied on the mouse neuroblastoma cells NG 108-15. TAM inhibited cell proliferation with an effective dose inducing a half maximum effect (ED50) of 2 microM and was cytotoxic from and beyond 2.5 microM. TAM accelerated the apparent inactivation of the whole cell K+ current with an apparent dissociation constant of 0.46 microM, and shifted the peak K+ conductance-voltage curve towards negative voltages with an apparent dissociation constant of 1.07 microM. The K+ flux at the resting potential, calculated from the time integral of the K+ current recorded during depolarizations, was decreased by TAM. The effect of TAM on the cell proliferation was perfectly correlated with the effect of TAM on the resting K+ flux. The results suggest that cell mitosis is, in some way, controlled by the functioning of K+ channels and that the antitumour action of tamoxifen could be due to its interaction with K+ channels.

Animals↗
PubMed1995

Contrasting effects of tamoxifen and ICI 182 780 on estrogen-induced calbindin-D 9k gene expression in the uterus and in primary culture of myometrial cells.

Antiestrogens have a large range of tissue- and promoter-specific actions, many of which still remain unclear, particularly in the uterus. Thus, we have analyzed the effects of two antiestrogens, tamoxifen (TAM) and ICI 182 780 (ICI) on the uterine estrogen-responsive gene calbindin-D9k (CaBP9k), in the ovariectomized rat uterus, and in primary cultures of myometrial cells. In the ovariectomized rat uterus, estradiol (E2) or E2 plus TAM induced CaBP9k mRNA to the same levels in 6h. Rats given TAM alone had the same mRNA concentration, but maximal induction was obtained later, 12h after injection. ICI alone did not induce CaBP9k gene expression. Rats given E2 plus ICI had low uterine CaBP9k mRNA levels at 6-12h that became undetectable at 24h. Thus ICI has a full antagonistic effect on E2-induced CaBP9k gene. Estradiol receptor (ER) assays showed that TAM had a partial antagonist effect, while ICI had a full antagonist effect on the ER. We also analyzed the effect of TAM and ICI on CaBP9k gene expression in primary cultures of myometrial cells. The effects were similar to those observed in whole uterus. Thus, TAM has mixed effects, being an agonist for CaBP9k gene induction, and an antagonist for ER. ICI antagonizes the effects of E2 on the CaBP9k gene in myometrial cells and in the intact uterus, but in a way that does not involve a decrease in the cellular content of ER. Instead, it interferes with at least one of the events leading to transcriptional activation.

Animals↗
PubMed2004

Protection of tamoxifen against oxidation of mitochondrial thiols and NAD(P)H underlying the permeability transition induced by prooxidants.

The effects of tamoxifen (TAM) were studied on the mitochondrial permeability transition (MPT) induced by the prooxidant tert-butyl hydroperoxide (t-BuOOH) or the thiol cross-linker phenylarsine oxide (PhAsO), in the presence of Ca2+, in order to clarify the mechanisms involved in the MPT inhibition by this drug. The combination of Ca2+ with t-BuOOH or PhAsO induces mitochondrial swelling and depolarization of membrane potential (deltapsi). These events are inhibited by cyclosporine A (CyA), suggesting the inhibition of the MPT. The pre-incubation of mitochondria with TAM also prevents those events and induces a time-dependent reversal of deltapsi depolarization following MPT induction, similarly to CyA. Moreover, TAM inhibits the Ca2+ release and the oxidation of NAD(P)H and protein thiol (-SH) groups promoted by t-BuOOH plus Ca2+. On the other hand, the MPT induced by PhAsO plus Ca2+ does not induce -SH groups oxidation, supporting the notion that MPT induction by this compound is not mediated by the oxidation of specific membrane proteins groups. However, TAM also inhibits the PhAsO induced MPT, suggesting that this drug may inhibit this phenomenon by inhibiting PhAsO binding to -SH vicinal groups, implicated in the MPT induction. These data indicate that the MPT inhibition by TAM may be related to its antioxidant capacity in preventing the oxidation of NAD(P)H and -SH groups or by blocking these groups, since the oxidation of these groups increases the sensitivity of mitochondria to the MPT induction. Additionally, they suggest an MPT-independent pathway for TAM-induced apoptosis and a potential ER-independent mechanism for the effectiveness of this drug in the cancer therapy and prevention.

Animals↗
PubMed2003

Application of a trityl-based radical probe for measuring superoxide.

The use of triarylmethyl (trityl) free radical, TAM OX063, for detection of superoxide in aqueous solutions by electron paramagnetic resonance (EPR) spectroscopy was investigated. TAM is paramagnetic (EPR active), highly soluble in water and exhibits a single sharp EPR peak in aqueous media. It is also highly stable in presence of many oxidoreductants such as ascorbate and glutathione that are present in the biological systems. TAM reacts with superoxide with an apparent second order rate constant of 3.1 x 10(3) M(-1) s(-1). The specific reactivity of TAM with superoxide, which leads to loss of EPR signal, was utilized to detect the generation of superoxide in various chemical (light/riboflavin/electron/donor), enzymatic (xanthine/xanthine oxidase), and cellular (stimulated neutrophils) model systems. The changes in the EPR line-width, induced by molecular oxygen, were utilized in the simultaneous determination of consumption of oxygen in the model systems. The effects of flux of superoxide and concentration of TAM on the efficiency of detection of superoxide were studied. The use of TAM for detection of superoxide offers unique advantages namely, (i) the utilization of very low concentration of the probe, (ii) its stability to bioreduction, and (iii) its use in the simultaneous determination of concentrations of superoxide and oxygen.

Electron Spin Resonance Spectroscopy↗
PubMed2005

Co-expression of steroid hormone receptors (estrogen receptor alpha and/or progesterone receptors) and Her2/neu (c-erbB-2) in breast cancer: clinical outcome following tamoxifen-based adjuvant therapy.

In breast cancer patients, the expression of steroid hormone receptors (HR:ERalpha/PR) appears inversely correlated with Her2/neu (not all reports agree on this negative correlation). Moreover, some but not all studies suggest that HR+/Her2/neu+ patients have a poor response to endocrine therapy, making this special group a matter of debate. In this prospective study we have analyzed the clinical outcome of our HR+/Her2/neu+ patients (n=51) selected from 516 consecutive stages I-II cases, with a follow-up 5-10 years (mean 7.3), treated with standard adjuvant therapy with tamoxifen (TAM) (TAM alone or TAM after chemotherapy). This group was compared with the HR+/Her-2/neu- patients (n=129) treated also with TAM. The tumor biopsies were studied by immunohistochemistry. We found that the association HR+/Her2/neu- was 2.5 times higher than the association HR+/Her2/neu+ (25% versus 9.9%, respectively). Our study also showed that the disease free survival (DFS) of the patients co-expressing HR and Her2/neu was significantly lower than those expressing HR but lacking of Her2/neu (p<0.001). A similar result was obtained when the overall survival (OS) was evaluated (p=0.001). All of these patients received hormone therapy with TAM, alone or after chemotherapy. When the analysis was performed in the patients treated with TAM alone, again the expression of Her-2/neu had a negative impact on both the DFS and the OS (p<0.05).

Adult↗
PubMed2005

Biomonitoring of heavy metals and trace organics using the intertidal mussel Perna viridis in Hong Kong coastal waters.

This paper presents the results of a 6-year (1998-2003) survey of trace toxics in the intertidal mussel Perna viridis conducted by the Hong Kong Environmental Protection Department. Concentrations of heavy metals and trace organics were measured in the soft bodies of P. viridis collected from five sites in Hong Kong waters, i.e. Wu Kai Sha (Tolo Harbour), Ma Wan (Northwest), Tsim Sha Tsui (Victoria Harbour), Tai Tam (Hong Kong South) and Lamma Island (Southern Waters) in order to establish the spatial patterns of contaminants in mussels. Among the metals analysed, Cd showed a significant concentration gradient in Hong Kong waters. The levels of Cd in P. viridis were significantly higher at Ma Wan as compared to the other sites studied. Ma Wan also had relatively higher concentrations of Pb. Mn concentrations were particularly prominent at Wu Kai Sha. Significantly higher concentrations of Hg and Cu were recorded at Tai Tam and Tsim Sha Tsui. Tai Tam and Wu Kai Sha had higher levels of V; whereas higher Ni concentrations were recorded at Lamma Island and Tai Tam. No clear spatial patterns for Al, As, Cr, Fe and Zn were observed. Higher concentrations of PAHs in P. viridis were observed around urban centres impacted by sewage discharges (e.g. Tsim Sha Tsui); whereas higher PCB levels were found not only in Tsim Sha Tsui but also in less urbanised areas such as Lamma Island and Tai Tam, suggesting that these may be due to non-sewage related inputs. The study also shows that Northwest and Southern waters are subject to a higher degree of DDT pollution compared with other sites. Of the 17 dioxin compounds analysed, positive data were mostly recorded for two compounds which are of low toxicity (i.e. OCDD and 1,2,3,4,6,7,8-HpCDD) whereas the most toxic congeners (i.e. 2,3,7,8-TCDD and 1,2,3,7,8-PeCDD) were not detected in the 6 years of monitoring. In general, the levels of OCDD in P. viridis were found to be higher in Tai Tam and Lamma Island in Southern Waters of Hong Kong. This study found that the levels of some highly toxic heavy metals (i.e. Cd, Hg and Pb) in the mussel P. viridis did not exceed the recommended limits for shellfish as food in Hong Kong (i.e. Cd: 2.0 ppm; Hg: 0.5 ppm; Pb: 6.0 ppm wet weight). The levels of As and Ni in P. viridis were also well below the action limits set by the US FDA (i.e. As: 86 ppm; Ni: 80 ppm wet weight). DDT and PCB contaminations in P. viridis were below the concentrations of concern. Compared with data obtained in the 1980s, the current levels of DDTs in P. viridis were 4-16 times lower; whereas Pb concentrations recorded in Tsim Sha Tsui have also been lowered significantly. This is mainly related to reduction in local and regional pollution sources in the past 20 years.

Analysis of Variance↗
PubMed2005

Evaluation of leukocyte arylsulphatase a, serum interleukin-6 and urinary heparan sulphate following tamoxifen therapy in breast cancer.

Leukocyte arylsulphatase A (AS-A) was shown to be significantly high in newly-diagnosed breast cancer patients. Previous reports imply a connection between serum interleukin-6 (IL-6) and breast cancer, possibly through a modulation of enzymes involved in estrogen synthesis. Abnormal distribution of heparan sulphate proteoglycans (HSPGs) in malignant breast epithelial cells suggests that they play a key role in the regulation of cell growth. Estradiol is believed to be effective in modulating glycosaminoglycans (GAGs) and their depolymerizing enzymes. Therefore, in this study, attempts were made to evaluate the activity of leukocyte arylsulphatase A, serum interleukin-6, urinary GAGs and heparan sulphate (HS) in response to tamoxifen (TAM) therapy in mastectomised breast cancer patients. Thirty-four patients (aged 30-82 years) were administered TAM (20 mg twice daily). Blood and urine samples of each patient were collected three times (at the beginning, and in third and sixth month of TAM therapy), and biochemical parameters were measured. There was no difference between baseline leukocyte AS-A activity and that measured after three months. At the end of six months, enzyme activity was significantly higher than the former values (p=0.022), but within the reference intervals reported in the literature. Although this increase might imply a normalization, the duration of TAM therapy is not long enough to make a decision about either regression or aggravation of the disease. TAM did not have any effect on serum IL-6, urinary HS and GAG levels which may be due to insensitivity of these variables to TAM during the short period of therapy. Both urinary GAG and HS levels measured at sixth month exhibited a positive correlation with the baseline level of leukocyte AS-A (p=0.005 and 0.009, respectively), suggesting that positive responses to the drug might be seen in patients with low AS-A activity.

Adult↗
PubMed2006

Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen.

Pregnant CD1 mice received 85 ppm arsenite in the drinking water from gestation day 8 to 18, groups (n = 35) of male offspring were subsequently injected on postpartum days 1 through 5 with diethylstilbestrol (DES; 2 microg/pup/day) or tamoxifen (TAM; 10 microg/pup/day), and tumor formation was assessed over 90 weeks. Arsenic alone increased hepatocellular carcinoma (14%), adenoma (23%) and total tumors (31%) compared to control (0, 2 and 2%, respectively). Arsenic alone also increased lung adenocarcinoma, adrenal cortical adenoma and renal cystic tubular hyperplasia compared to control. Compared to arsenic alone, arsenic plus DES increased liver tumor incidence in mice at risk 2.2-fold and increased liver tumor multiplicity (tumors/liver) 1.8-fold. The treatments alone did not impact urinary bladder carcinogenesis, but arsenic plus TAM significantly increased formation of urinary bladder transitional cell tumors (papilloma and carcinoma; 13%) compared to control (0%). Urinary bladder proliferative lesions (combined tumors and hyperplasia) were also increased by arsenic plus TAM (40%) or arsenic plus DES (43%) compared to control (0%) or the treatments alone. Urinary bladder proliferative lesions occurred in the absence of any evidence of uroepithelial cytotoxic lesions. Urinary bladder lesions and hepatocellular carcinoma induced by arsenic plus TAM and/or DES overexpressed estrogen receptor-alpha, indicating that aberrant estrogen signaling may have been a factor in the enhanced carcinogenic response. Thus, in male CD1 mice, gestational arsenic exposure alone induced liver adenoma and carcinoma, lung adenocarcinoma, adrenal adenoma and renal cystic hyperplasia. Furthermore, DES enhanced transplacental arsenic-induced hepatocarcinogenesis. In utero arsenic also initiated urinary bladder tumor formation when followed by postnatal TAM and uroepithelial proliferative lesions when followed by TAM or DES.

Animals↗