There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues are also affected by the cytotoxic effects of these chemical agents. Fucoidan, a natural component of brown seaweed, has anti-cancer activity against various cancer types by targeting key apoptotic molecules. It also has beneficial effects as it can protect against toxicity associated with chemotherapeutic agents and radiation. Thus the synergistic effect of fucoidan with current anti-cancer agents is of considerable interest. This review discusses the mechanisms by which fucoidan retards tumor development, eradicates tumor cells and synergizes with anti-cancer chemotherapeutic agents. Challenges to the development of fucoidan as an anti-cancer agent will also be discussed.

In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT.

Background:Previous pooled analyses have reported an association between magnetic fields and childhood leukaemia. We present a pooled analysis based on primary data from studies on residential magnetic fields and childhood leukaemia published after 2000.Methods:Seven studies with a total of 10 865 cases and 12 853 controls were included. The main analysis focused on 24-h magnetic field measurements or calculated fields in residences.Results:In the combined results, risk increased with increase in exposure, but the estimates were imprecise. The odds ratios for exposure categories of 0.1–0.2 μT, 0.2–0.3 μT and ⩾0.3 μT, compared with <0.1 μT, were 1.07 (95% CI 0.81–1.41), 1.16 (0.69–1.93) and 1.44 (0.88–2.36), respectively. Without the most influential study from Brazil, the odds ratios increased somewhat. An increasing trend was also suggested by a nonparametric analysis conducted using a generalised additive model.Conclusions:Our results are in line with previous pooled analyses showing an association between magnetic fields and childhood leukaemia. Overall, the association is weaker in the most recently conducted studies, but these studies are small and lack methodological improvements needed to resolve the apparent association. We conclude that recent studies on magnetic fields and childhood leukaemia do not alter the previous assessment that magnetic fields are possibly carcinogenic.

We have developed an antibody-based method to assess plasma uptake of a proprietary Undaria-derived fucoidan galactofucan sulfate (GFS(TM)) after oral ingestion by human volunteers. Fucoidans have high-molecular-weights but exert biological effects in experimental animals after oral intake. By using a novel antibody raised against sulfated polysaccharides, we carried out a competitive ELISA to quantitate GFS in plasma samples from healthy volunteers who ingested 3 g/day of whole Undaria containing 10% GFS fucoidan, purified 75% GFS fucoidan, or 3 g of a nonsulfated placebo polysaccharide over 12 days. Increased reactivity to the novel antibody, as measured against preingestion levels, was detected at all time points. Assuming the measured material to be intact GFS, the concentration detected (median) was 4.002 and 12.989 mg/l when 3 g of 10% or 75% pure fucoidan was ingested orally over a period of 12 days, respectively. High-molecular-weight fucoidan can be detected in plasma using an ELISA competitive assay based on a novel antibody to sulfated polysaccharides.

Summary:In this prospective multicentre trial, 90 patients undergoing autologous stem cell transplantation (ASCT) were randomised to receive (n ¼ 43) or not receive (n ¼ 47) amifostine 910 mg/m 2 prior to melphalan 200 mg/m 2 . Patients were monitored for regimen-related toxicity, engraftment, supportive care, response and survival. Both groups underwent ASCT at a median of 8 months from diagnosis and were matched for disease characteristics, prior therapy and pre-ASCT disease responsiveness. Amifostine infusional side-effects were frequent, occurring in 65% of patients, but of mild severity. Amifostine use was associated with a reduction in the median grade of oral mucositis (1 vs 2, P ¼ 0.01) and the frequency of severe (WHO grades 3 or 4) mucositis (12 vs 33%, P ¼ 0.02), but no reduction in the requirement for parenteral nutrition or analgesic use. Conversion to complete remission post-ASCT occurred in 30 and 14% of the amifostine and control groups, respectively (P ¼ 0.09). With a median follow-up of 35 months, there was no statistically significant difference between the median progression-free or overall survival times for the two groups. We conclude that amifostine can be safely administered prior to highdose melphalan and significantly reduces the frequency and severity of therapy-induced oral mucositis. Bone Marrow Transplantation (2005) 35, 971-977.

DiscussionCarbenicillin is an established antibiotic for infections due to two difficult groups of organisms-Ps. aeruginosa and the indolepositive Proteus spp.4 Non-,3-lactamase-producing E. coli are very susceptible to carbenicillin and Str. faecalis moderately so. Though carbenicillin is particularly useful against Ps. aeruginosa high parenteral doses (up to 30 g/day) may be needed to treat systemic infections with this organism. High urinary concentrations of carbenicillin have been reported,5 with intramuscular doses of 500 mg giving concentrations greater than 500 mg/l. Such levels will eradicate sensitive Ps. aeruginosa (M.I.C.< 100 mg/l) but the injections are often painful and the patient usually needs to be in hospital.Serum levels in volunteers and patients after oral carfecillin were found to be insufficient to treat systemic infection with Ps. aeruginosa, even when renal function was impaired, but urinary levels were sufficient to suggest that urinary infections might be eradicated.In severe renal failure the mean serum half life of carbenicillin is only 10-20 hours,2 which is short compared with that of gentamicin particularly as our dose was lower and given for seven days instead of 14. Our patients also had a high prevalence of urinary tract abnormalities. The overall cure rate with indanyl carbenicillin in the series of Ries et al. 9 was 50% as compared with 60% in our series, though no pseudomonas infections were treated with indanyl carbenicillin in the former series as compared with 12 in ours. Ps. aeruginosa rarely causes primary, uncomplicated urinary tract infection but it may cause infection secondary to other urinary tract conditions or operations where catheterization may have been necessary."' The only antibiotic therapy available to such patients is by the parenteral route, which usually means a stay in hospital. The availability of a well-tolerated oral agent for such cases represents a therapeutic advance. Further studies with carfecillin are necessary, and possibly a longer course of treatment should be given in difficult cases, but this drug promises to be a useful oral treatment of urinary infections when the choice of effective antibiotics is limited.The formulation of carfecillin to be marketed in the United Kingdom will differ slightly from that used in our studies reported here, the main change being improved oral absorption.3 Its performance in curing infection will probably be at least as good as that of the previous formulation, but side effects and tolerability will need to be reassessed.

Fucoidan, a natural component of seaweeds, is reported to have immunomodulatory and anti-tumor effects. The mechanisms underpinning these activities remain poorly understood. In this study, the cytotoxicity and anti-tumor activities of fucoidan were investigated in acute myeloid leukemia (AML) cells. The human AML cell lines NB4, KG1a, HL60, and K562 were treated with fucoidan and cell cycle, cell proliferation, and expression of apoptotic pathways molecules were analyzed. Fucoidan suppressed the proliferation and induced apoptosis through the intrinsic and extrinsic pathways in the acute promyelocytic leukemia (APL) cell lines NB4 and HL60, but not in KG1a and K562 cells. In NB4 cells, apoptosis was caspase-dependent as it was significantly attenuated by pre-treatment with a pan-caspase inhibitor. P21/WAF1/CIP1 was significantly up-regulated leading to cell cycle arrest. Fucoidan decreased the activation of ERK1/2 and down-regulated the activation of AKT through hypo-phosphorylation of Thr(308) residue but not Ser(473). In vivo, a xenograft model using the NB4 cells was employed. Mice were fed with fucoidan and tumor growth was measured following inoculation with NB4 cells. Subsequently, splenic natural killer (NK) cell cytotoxic activity was also examined. Oral doses of fucoidan significantly delayed tumor growth in the xenograft model and increased cytolytic activity of NK cells. Taken together, these data suggest that the selective inhibitory effect of fucoidan on APL cells and its protective effect against APL development in mice warrant further investigation of fucoidan as a useful agent in treatment of certain types of leukemia.

Seaweed-derived heparin-like substances such as fucoidan have been extensively studied in vitro as potential blood anticoagulants. However, there have been no human studies investigating the anticoagulant activity of fucoidan when administered orally. This pilot clinical trial was aimed to assess the safety and clinical effects of fucoidan ingestion on hemostasis as well as study its in-vitro anticoagulant activity. In a single-blinded clinical trial, a total of 20 human volunteers were allocated to both the placebo group (n = 10) who ingested 3 g of guar gum capsules and to the active treatment group (n = 10) who ingested 3 g of 75% fucoidan capsules for 12 days. Platelet indices, activated partial thromboplastin time, antithrombin-III, thrombin time, prothrombin time, and antifactor-Xa were analyzed according to standard methods. In vivo, activated partial thromboplastin time increased from 28.41 to 34.01 s (n = 10, P = 0.01), thrombin time decreased from 18.62 to 17.55 s (n = 10, P = 0.04), and antithrombin-III increased from 113.5 to 117% (n = 10, P = 0.03). The in-vitro fucoidan anticoagulant activity was found prominent. It increased activated partial thromboplastin time, thrombin time, and prothrombin time, whereas antithrombin-III decreased. In-vivo effect of fucoidan on hemostasis was not obvious probably due to low intestinal absorption. Thus, fucoidan in the form used in this study does not seem to have an oral anticoagulant activity, but it has a very strong in-vitro anticoagulant activity.