Japanese-specific see more costs, health utilities and disease transition rates were used. Sustained viro-logic response rates at 24 weeks (SVR24) for DCV+ASV were 79.5 %in NRs and PRs and 87 %in IFN-ineligible patients. SVR24 rates for TVR+pegIFNa/RBV and SMV+pegIFNa/RBV were 42.8 %and 57.6%, respectively, for both NRs and PRs. Results The table reports total expected HCV related costs and QALE driven by changes in SVR stratified by treatment scenario

and cohort age. Conclusion Treatment options are limited for patients who have previously failed to achieve SVR with IFN-based therapy or who are IFN-ineligible. The superior levels of SVR associated with DCV+ASV are associated with significant savings in projected disease costs and increased QALE,

even in those of more advanced age. Total HCV Lifetime Costs* *Excluding cost of HCV therapy Disclosures: Philip McEwan – Consulting: Bristol-Myers Squibb Yong Yuan – Employment: Bristol Myers Squibb Company Anupama Kalsekar – Employment: Bristol Myers Squibb Ann C. Tang – Employment: Bristol-Myers Suqibb Hiromitsu Kumada – Speaking and Teaching: Bristol-Myers Squibb,Pharma International, MSD, Dainippon Sumitomo, Tanabe Mitsubishi, Ajinomoto The following selleck screening library people have nothing to disclose: Thomas Ward, Isao Kamae, Mariko Kobayashi, Sachie Inoue Introduction The therapy landscape of treatment

for hepatitis C virus (HCV) has evolved considerably in recent years, while the degree of SVR improvement is diminishing between newer treatments and its incremental impacts on economic outcomes are still unknown Given these challenges this study was designed to quantify the expected cost-offset and improvement in health outcomes associated with unit increments in SVR independent of the specific HCV treatment used. Methods A published Markov lifetime model with a payer perspective was used to estimate the reduction in complications costs and increase in quality adjusted life expected (QALE) associated with unit increases (per %point) in SVR. Analysis was stratified into patient groups aged 40, 50, 60 and 70 years across fibro-sis stages F0 through F4. US specific MCE公司 and previously published disease transition rates, costs of complications (2013 values) and health related utility were utilised with both future costs and benefits discounted at 3%. Results Reported in the table are the expected increase in QALE and decrease in complication-related costs associated with an increase of one SVR %point stratified by age and fibrosis stage: Conclusion Through the presentation of expected costs offsets and health benefits (QALE) associated with a one % point improvement in SVR we enable the value associated with an arbitrary SVR level to be derived.

Advances in haemophilia treatment, such as the availability of recombinant factor concentrates [2] and the emphasis on prophylaxis to avoid bleeding episodes [3-7] have led to improved haemophilia A treatment outcomes [8, 9]. Adherence to prophylaxis is correlated with reduced bleeds, less joint damage and improved health-related quality of life (HRQoL) [10-12]. Although compliance with prescribed treatment regimens is crucial for achieving optimal therapeutic benefit and avoiding potential

costly complications, patient RG7204 price treatment decisions are multifaceted and influenced by both nonfinancial and financial factors. Common nonfinancial obstacles to care in the general population may also be relevant for haemophilia A patients. These barriers may include scheduling conflicts, lack of transportation assistance and

the availability of health care providers (HCPs) who offer comprehensive care [13, 14]. Financial barriers, such as insurance click here coverage and out-of-pocket (OOP) costs associated with treatment [15], may also influence treatment behaviours [14, 16]. The recent economic downturn in the USA, which began around December 2007, has increased the number of unemployed or underemployed Americans to a peak unemployment rate of 10% in 2010 [17]. As health insurance is commonly provided to families by employers, many of these under- or unemployed families lost their health insurance when they lost their jobs. The number of patients without health insurance increased between 2008 and 2009 [18]. Previous research has provided some insight on the impact of the economic downturn on the general population and patients with chronic diseases (e.g. heart disease, diabetes and cancer) and HCP behaviour for these patients [19, 20]. Due to the economic downturn, under- or uninsured Americans may delay filling prescriptions,

postpone or skip a recommended medical visit, test, or treatment and/or skip doses of medicine [21, 22]. Although the economic downturn may have also impacted the haemophilia A community, its impact on treatment decision-making among patients/caregivers with haemophilia A and their 上海皓元 HCPs is not known. It also remains unknown whether and how the recent economic downturn has prevented certain haemophilia patients from accessing appropriate haemophilia care. To address rising health care costs and to improve Americans’ access to health care, a comprehensive health care reform legislation, the Patient Protection and Affordable Care Act (ACA), was signed into law on March 23, 2010. The ACA includes provisions to expand access to health insurance, improve the quality and comprehensiveness of coverage and make coverage more affordable for all Americans [23].

Large cholangiocytes, from large ducts, express secretin receptors on the basolateral membrane and express cystic fibrosis transmembrane conductance regulator (CFTR) and the HCO3−/Cl− anion exchanger 2 (AE2) on the apical membrane,2-4 and hence respond to secretin with an increase in [cAMP] (intracellular cyclic adenosine monophosphate concentration), and subsequent Cl− and HCO3− efflux into the lumen. Conversely, small cholangiocytes, PF-2341066 from small ducts, do not express secretin receptors, CFTR, or HCO3−/Cl− exchanger and do not exhibit a secretory response

to secretin.3 In human liver, parallel to the findings observed in the rat and mouse, secretin-stimulated duct secretory activity is heterogeneous, because only medium and large interlobular bile ducts express the Cl−/HCO3− exchanger AE2.5 Recently, secretion mediated by extracellular nucleotides (e.g., adenosine triphosphate [ATP]) acting on purinergic (P2) receptors on the luminal membrane of biliary epithelial cells has emerged as functionally important. ATP is present in bile,6 and binding of ATP to P2 receptors increases K+7,8 and Cl− efflux from isolated cholangiocytes9, ZD1839 manufacturer 10 and dramatically increases transepithelial secretion

in biliary epithelial monolayers.10, 11 Indeed, the magnitude of the secretory response to ATP is two-fold to three-fold greater than that to cAMP.10 Interestingly, recent evidence suggests that even cAMP-stimulated bile flow is mediated by ATP release into the duct lumen and stimulation of apical P2 receptors.12 Together, these studies challenge

and extend the conventional model that centers on the concept that cAMP-dependent opening of CFTR-related Cl− channels is the driving force for cholangiocyte secretion. 上海皓元 Rather, the operative regulatory pathways appear to take place within the lumen of intrahepatic ducts, where release of ATP into bile is a final common pathway controlling ductular bile formation. In light of recent studies demonstrating that the mechanical effects of fluid-flow or shear stress at the apical membrane of biliary epithelial cells is a robust stimulus for ATP release,13 a model emerges in which mechanosensitive ATP release and Cl− secretion is a dominant pathway regulating biliary secretion. Although cholangiocytes express a repertoire of both P2X and P2Y receptors,11, 14, 15 it is unknown if expression differs between small and large cholangiocytes and/or if functional differences exist in ATP release and signaling along the bile duct. The aim of the current studies therefore was to determine if a potential P2 signaling axis may exist along the bile duct by evaluating mechanosensitive ATP release and exocytosis, P2 receptor expression and function, and secretion mediated by extracellular nucleotides in both small (MSC) and large (MLC) mouse cholangiocytes.

e. arginine) or mutant (i.e. glutamine or histidine). In see more addition, substitutions at amino acids 2290–2248 of the NS5A region (interferon-sensitivity determining region) were determined as described previously.[31] Amino acid substitutions in this region were defined as wild type (0 or 1) or non-wild type (≥2). Genomic DNA was extracted from whole blood using the MagNA Pure LC and a DNA Isolation Kit (Roche Diagnostics). The genetic polymorphism near the interleukin-28B (IL28B) gene,[32, 33] rs8099917, was genotyped by real-time PCR

using the TaqMan SNP Genotyping Assays and the 7500 Fast Real-Time PCR System (Applied Biosystems, Foster City, CA, USA). The rs8099917 genotypes were classified as TT (major genotype) or non-TT (minor genotype: TG or GG). Continuous variables are expressed as means and standard deviations. Continuous data were analyzed using the non-parametric Mann–Whitney U-test. Categorical data were analyzed using the χ2-test with a Yates correction or Fisher’s exact test. Univariate and multivariate

logistic regression analyses were performed to identify factors that significantly contributed to SVR. Odds ratios (OR) and 95% confidence intervals (95% CI) were also calculated. All P-values for statistical tests were two-tailed. The levels of significance and marginal significance were set at P < 0.05 and P < 0.15, respectively. Variables showing statistical or marginal significance in univariate analysis were entered into multivariate Selleckchem FK506 logistic regression analyses to identify significant independent predictive factors of SVR. All statistical analyses were performed using SPSS version 17.0 (IBM-SPSS, Chicago, IL, USA). In this study, the adherence to each drug was excluded for the difference of treatment duration and the stopping rules. PATIENT CHARACTERISTICS ARE summarized in Table 1. Of the

103 patients, 57 (55.3%) and 46 (44.7%) were partial and null responders, respectively. Partial responders had significantly higher platelet counts than null responders (P = 0.0126). α-Fetoprotein levels were significantly lower in partial responders than null responders (P = 0.0202). No other baseline factors differed significantly between groups. Regarding treatment outcomes of TVR-based triple combination therapy, 58 patients (56.3%) achieved SVR, 23 (22.3%) showed relapse, 16 (15.5%) MCE showed VBT and six (5.8%) showed non-response. Patients were stratified according to previous treatment response and regimen. Among the 50 partial responders treated with T12PR24, 35 (70.0%) achieved SVR, 12 (24.0%) showed relapse and three (6.0%) showed VBT. Among the seven partial responders treated with T12PR48, six (85.7%) achieved SVR and one (14.3%) showed VBT. Among all partial responders, the SVR rate was slightly higher with T12PR48 than T12PR24 (6/7 [85.7%] vs 35/50 patients [70.0%]), though not statistically significant (P = 0.6763) (Fig. 1).

Narrow intercostal spaces are a known limitation of FibroScan. In clinical practice, various patient maneuvers can be used to widen the intercostal space and allow unobstructed readings. Several other factors have been shown to limit the performance of TE in the assessment of hepatic fibrosis. Ascites prevents the propagation of shear waves, thereby preventing the acquisition of a liver stiffness. Furthermore, liver stiffness

increases during the alanine aminotransferase (ALT) flares of chronic viral hepatitis and during liver injury associated with acute viral, drug related or autoimmune causes.11 An appreciation of the impact mTOR inhibitor of hepatic necro-inflammation on liver stiffness might be critical in the accurate interpretation of TE. Several groups have shown that the performance of FibroScan varies according to ALT levels.12 In addition

to these factors, elevated LSM independent of hepatic fibrosis is seen in conditions including cholestasis13 and congestive cardiac failure.14 Despite the aforementioned limitations, TE is gaining popularity throughout the world as a tool for predicting or ruling out cirrhosis, particularly in patients with chronic hepatitis C. It is also gaining acceptance in other chronic liver diseases, and much attention of late has been turned towards staging fibrosis in patients with non-alcoholic fatty liver disease. Obesity is common in this patient MCE group, and is becoming an increasingly prevalent problem in many of our patients with other liver Bafilomycin A1 chemical structure diseases, including hepatitis C. Because obesity accounts for the majority of unreliable or failed LSM, future studies will undoubtedly need to use the XL probe to avoid excluding this important patient subgroup. In summary, FibroScan has consistently been shown to be superior to other non-invasive assessment techniques in the prediction of advanced fibrosis/cirrhosis.6,15 Transient elastography is quick, reproducible and non-invasive, and thus is likely to be increasingly

used as a clinical tool in the assessment of hepatic fibrosis. As our collective experience with FibroScan grows, its role in clinical practice will become further clarified. “
“Inflammation is one of the most characteristic features of chronic liver disease of viral, alcoholic, fatty and autoimmune origin. Inflammation is typically present in all disease stages, and associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma. In the past decade, numerous studies have contributed to improved understanding of the links between hepatic inflammation and fibrosis. Here, we review mechanisms that link inflammation with the development of liver fibrosis, focusing on the role of inflammatory mediators in hepatic stellate cell (HSC) activation and HSC survival during fibrogenesis and fibrosis regression.

Chronic ethanol exposure also led to an overall downward shift in the expression of Wnt 1, Fzd3, Lef1, Bcl9, Wisp 1, Sfrp5, and Wif1. The expression of Ccnd1, a major regulator of the

cell cycle, was elevated in the control group at 24 hours. However, STA-9090 research buy ethanol treatment caused a delayed response and peak expression occurred at 72 hours post-PH. Treatment with PPARδ agonist rescued the ethanol-induced depression of Wnt gene expression for genes including Wnt1, Wnt7a, Fzd3, Lef-1, Tcf7l2, Bcl9, Ccnd1, Axin2, Wif1, and Sfrp2. Conclusions: These observations demonstrate that long-term ethanol consumption inhibits Wnt signaling, leading to an impairment of liver regeneration. Treatment with PPARδ agonist ameliorated this effect, suggesting that improvement of liver function in chronic ALD requires

the restoration of Wnt signaling in addition to insulin/IGF signaling. Disclosures: The following people have nothing to disclose: Chelsea Q. Xu, Suzanne M. de la Monte, Jack R. Wands, Miran Kim Using selected-ion flow-tube mass spectrometry (SIFT-MS), precise identification of trace gases in human breath can be achieved. Aim: To determine whether concentration of volatile compounds in breath correlates with diagnosis and severity of liver disease in pts with alcoholic hepatitis (AH). Methods: We prospectively recruited pts with liver disease into two groups: liver cirrhosis with AH (N=40) and liver cirrhosis with acute decompensation (AD) from medchemexpress etiologies other than alcohol (N=40). A healthy control group without liver disease was identified (N=43). Using PF-6463922 order SIFT-MS, precise identification of volatile compounds in breath

in parts per billion ranges was achieved in fasting state. Results: Of 14 pre-selected breath compounds, we identified 6 compounds that were elevated in pts with liver disease compared to healthy control. Those include 2-propanol, acetaldehyde, acetone, ethanol, pentane and trimethylamine (TMA). The levels of TMA, acetone and pentane, in particular, in breath were remarkably higher in pts with AH compared to those with AD and to healthy volunteer (p<0.001). Using ROC curve, we developed model for diagnosis of AH that included breath levels of TMA, Acetone and Pentane (TAP model). TAP provided excellent prediction accuracy for diagnosis of AH (AUC=0.93) with 97% sensitivity and 72% specificity for TAP score of 28. The levels of breath TMA moderately correlated with severity of AH as presented by MELD score [rho (95%CI); 0.38 (0.07, 0.69),p=0.018]. Isoprene and ethanol in breath were associated with survival in AH. Conclusion: Breathprint may provide non-invasive method for diagnosis of AH and may provide independent prognostic value in patients with AH. Background: Sestrins (Sesns) are a small family of stress-sensitive genes that control lipid metabolism. Chronic alcohol feeding leads to the alteration in lipogenic genes; which are under the regulation of Sesns.

AZA-induced hepatotoxicity should be suspected in patients with elevated 6-MMP (regardless of 6-TGN levels). The addition of allopurinol with appropriate AZA dose reduction may correct AZA-induced hepatoxicity

and induce remission. “
“See article in J. Gastroenterol. Hepatol. 2010; 25: 544–547 Two recent large-scale, prospective studies, both in high risk populations, have reported Helicobacter pylori infection as a definite risk factor for the development of gastric cancer.1,2 However, the premise that treatment of H. pylori infection is an appropriate target for prevention of gastric cancer is still uncertain. Three randomized, placebo-controlled trials performed in China and Columbia demonstrated no significant protective effect by H. pylori eradication,3–5 whereas contradictory results high throughput screening compounds have emerged out of three Japanese studies published recently,6–8 LEE011 indicating that H. pylori eradication may prevent the development of gastric cancer significantly, even in patients with precancerous gastric lesions. The contradictory results can be explained by the fact that, unlike the studies from China, protective studies from Japan were neither randomized nor placebo-controlled.

However, the common feature of each Japanese study was that no gastric cancers developed after eradication treatment in patients without precancerous gastric lesions at entry. Stated the other way around, all gastric cancer cases appeared in patients who had intestinal metaplasia and/or epithelial MCE dysplasia at trial entry before H. pylori eradication. This observation reminds us that earlier eradication therapy must be used in high-risk populations to completely abolish overall gastric cancer risk. Another key issue regarding the influence of H. pylori eradication on gastric cancer prevention is the fact that atrophic gastritis is reversible after H. pylori eradication, leading to the hypothesis that H. pylori eradication could

retard or reverse gastric carcinogenesis before it reaches the stage of H. pylori-associated intestinal metaplasia and/or dysplasia.9 As clear evidence of the merit of H. pylori eradication, Fukase K et al.10 have published important results from a study where, following endoscopic resection of early gastric cancer, a group of patients in a randomized control trial were subjected to H. pylori eradication treatment and monitored at different time intervals. At 3 years, metachronous gastric cancer had developed in only 9 of 255 patients in the eradication group compared with 24 of 250 patients in the control group, a significant difference with indicates that prophylactic eradication of H. pylori in atrophic gastritis can substantially reduce gastric cancer rates. In this issue of the Journal of Gastroenterology and Hepatology, Toyokawa T et al.11 reported that H.

g. certain SNPs), altering the function of key proteins involved in the pathogenesis of INH-induced DILI. Furthermore, chemical

factors (e.g. comedication) may also greatly influence the extent of INH-induced DILI. Other risk factors, including underlying diseases or inflammatory episodes, will not be discussed, as they are outside the scope of this review. Traditionally, the acetylator phenotype (determined by NAT2 polymorphisms) has beta-catenin inhibitor been implicated as a determinant of susceptibility to INH-induced DILI. This makes sense because NAT2 is involved in INH biotransformation. However, acetylation leads to both bioactivation (acetylhydrazine formation) and detoxication (diacetylhydrazine formation) (Fig. 2). Therefore, it is not surprising that some studies identified CDK inhibitor the fast acetylator phenotype as

a determinant of susceptibility,[70, 71] while others, more recently, linked the poor acetylator phenotype with an increased risk.[72, 73] Thus, the causal role of the NAT2 haplotype has remained controversial; furthermore, the current concept no longer implicates NAT2 polymorphisms as a major risk factor, particularly because these polymorphisms (e.g. coding for a slow acetylator phenotype) are extremely frequent in populations. Similarly, the role of CYP2E1 variants has remained controversial.[73] Since a direct role of CYP2E1 in the hepatic toxicity of INH has been questioned,[29] and because a number of INH metabolites can even be generated independently of CYPs,[28] the focus has somewhat shifted away from CYP2E1 being a major determinant of susceptibility. However, apart from the enzyme’s role in drug bioactivation/inactivation, two points are important: First, CYP2E1 is also expressed in mitochondria,[74] MCE公司 and second, CYP2E1 is one of the CYP forms that has been shown to generate relatively high levels of ROS;[75] therefore, it is possible that

the role of CYP2E1 could simply be in enhancing the extent of oxidant stress. Another genetic variant that has been analyzed for its role as a potential determinant of susceptibility is the glutathione S-transferase (GST) family. A recent meta-analysis examining the association between selective GST variants and the risk for INH-associated DILI found that individuals with a null-genotype in GSTM1 may have an increased risk, while patients with a null-genotype in GSTM1 did not.[76] The exact role of these polymorphisms are unclear; however, it can be surmised that functional GST dependence reflects the trapping of a reactive intermediate. Furthermore, in Japanese patients, an association has been found between certain gene mutations in one of the anti-oxidant pathways and INH-induced DILI.[77] These positive correlations include mutations in NOS2A (encoding for inducible nitric oxide synthase, iNOS) resulting in gain of function, which leads to increases in NO production.

We examined total RNA from normal liver tissues and HCCs by Northern analysis. For discrimination between G and aG HDV RNAs, HDV strand-specific hybridizations were employed (Fig. 2). The detection

of aG RNA is an ultimate proof of infection, because aG RNA is absent from the virions and only appears via RNA replication following HDV infection of hepatocyte.2 At the top panel of Fig. 2, it is shown that all three RNA samples extracted from normal LL tissues of either woodchuck M7724 (lane 1) or F7807 (lane 3), and from normal LM tissue of woodchuck M7788 (lane 2) were positive for aG RNA. Also, all HCCs assayed (i.e., HCC1 from woodchuck M7724 [lane 4]; HCC1, HCC3, HCC4, and HCC5 from woodchuck M7788 [lanes 5, 6, 7, and 8, respectively]; and HCC1 and HCC2 from woodchuck F7807 [lanes 9 and 10, respectively]) Nivolumab manufacturer were positive for aG RNA, and thus were infected with

wHDV. The levels of aG RNA in HCCs LY294002 purchase and in normal liver tissues were comparable. As anticipated, all RNA samples that tested positive for aG RNA were also positive for G RNA (Fig. 2, bottom panel). No aG and G RNA were detected in total RNA extracted from the HCCs of two control WHV carriers M7746 and M7747, which were not superinfected with wHDV (lanes 11 and 12). These findings obtained by Northern analyses were confirmed and extended using HDV strand-specific qPCR (Table 1). The RNAs from all normal and HCC tissues obtained from the MCE公司 superinfected animals during necropsy tested positive for both strands of HDV RNA. As anticipated, the G RNA levels were ≈7 to 27-fold higher than those of aG.2 In animal M7724, the HDV RNA levels in HCC1 were higher than those in normal LL, LM, and RL tissues. In woodchuck M7788 in the HCC3, HCC4, and HCC5 the levels of HDV RNA accumulation were higher than in surrounding normal liver tissues. The HCC1 (M7788) had HDV RNA levels comparable to those of normal tissues. Only HCC2 from the same animal had the lowest HDV RNA levels among all tissues analyzed. This may reflect a difference

in the susceptibility to infection related to the differentiation state of HCC. The levels of G RNA accumulation in HCCs of woodchuck M7807 were ≈4-fold lower than the average G RNA level in normal tissues. As expected, total RNA from HCC1s of WHV carriers M7746 and M7747 that were not superinfected with wHDV, and also the RNAs from the normal liver tissues and HCC1s of woodchucks M7724, M7788, and F7807, which were obtained during laparotomy prior to wHDV superinfection, were negative for HDV RNAs (data not shown). All HCCs including those identified prior to wHDV superinfection became HDV-positive following superinfection, and most of them appeared to be infected at least as efficiently as normal liver tissues.

IGF2R expression was significantly lower in non-risk allele than in risk allele cases (P = 0.012). There was neither a diabetes- nor a fat metabolism-related gene that was significantly associated with CRC cases with the risk allele at 8q24.

Conclusions:  SNP at 8q24 makes diabetes a risk factor of CRC via IGF2R, especially in genetically non-risk allele cases. We speculate that the risk allele of 8q24 might be risky enough that diabetes is not necessary to worsen the risk for CRC. The mortality and morbidity of colorectal cancer (CRC) are exponentially increasing in Japan, and CRC is now considered to be a national problem to be solved urgently. The identification of factors regulating the carcinogenesis and progression of CRC would contribute to preventing the occurrence of the cancer, as well as improving check details the clinical outcome of treatment of the disease. Several studies have identified single nucleotide polymorphisms Selleckchem Staurosporine (SNPs) that are intimately

connected with the onset of CRC. In their genome-wide association study for CRC cases, Tomlinson et al. examined 550 thousand SNPs in 930 cases of CRC with a familial history and identified rs6983267 at 8q24.21 as the most consecutive SNP to be strongly connected to the onset of CRC.1 This finding was confirmed by the additional screening of 7334 cases of CRC and revealed an odds ratio (OR) of 1.27 (P = 1.27 × 10−14).2 Zanke et al. investigated 100 thousand SNPs in 7480 cases of CRC and discovered SNPs at 8q24 (OR = 1.18, P = 1.41 × 10−8) that were connected to the incidence of CRC.3 However, the relation between SNPs, including 8q24, associated with CRC and its carcinogenesis has not been elucidated for the reason that there is no coding region at the locus where the SNP exists. MYC is a strong candidate gene because it lies 116 kb telomeric to rs6983267, outside the haplotype block showing an association with CRC risk, but any significance was observed between the SNP at 8q24 and CRC. Although a

number of SNPs 上海皓元 are reported to be associated with CRC, the definitive mechanism of carcinogenesis has not been revealed yet. Moreover, there is little study of either SNPs being connected to the cause of CRC in Asia or about the relationship between SNP analysis and epidemiology. There are several epidemiologic and/or environmental studies of the carcinogenesis of CRC. In general, diabetes mellitus or metabolic syndrome is a crucial factor for CRC, as well as several other cancers.4 Diabetes may influence the neoplastic process by several mechanisms, including hyperglycemia, hyperinsulinemia (either endogenous because of insulin resistance or exogenous related to administered insulin or insulin secretogogs) and chronic inflammation.5 The recent resurgence of interest in the Warburg hypothesis and cancer energetics6 emphasizes the dependence of many cancers on glycolysis for energy, creating a high requirement for glucose.