Dairy product intake and mortality in a cohort of 70-year-old Swedes: a contribution to the Nordic diet discussion.

INTRODUCTION: Conflicting results in the literature exist on the role of dairy products in the context of a Nordic Healthy Diet (NHD). Two recent Swedish studies indicate both negative and positive associations with total mortality when comparing key dairy products. There is no consensus about how to include these foods into the NHD. PURPOSE: To study consumption of cheese and milk products (milk, sour milk and unsweetened yoghurt) by 70-year-old Swedes in relation to all-cause mortality. METHODS: Cox proportional hazard models, adjusted for potential confounders and stratified by follow-up duration, were used to assess the prediction of all-cause mortality by the above foods. The associations of fat from cheese and milk products with mortality were tested in separate models. RESULTS: Cheese intake inversely predicted total mortality, particularly at high protein intakes, and this association decreased in strength with increasing follow-up time. Milk products predicted increased mortality with stable HRs over follow-up. The association between milk products and mortality was strongly influenced by the group with the highest consumption. Fat from cheese mirrored the protective association of cheese intake with mortality, whereas fat from milk products predicted excess mortality, but only in an energy-adjusted model. CONCLUSION: Based on our results, it may be argued that the role of dairy products in the context of a Nordic healthy diet should be more clearly defined by disaggregating cheese and milk products and not necessarily focusing on dairy fat content. Future epidemiological research should consider dairy products as disaggregated food items due to their great diversity in health properties.

Prospective associations between dietary patterns and high sensitivity C-reactive protein in European children: the IDEFICS study.

PURPOSE: This prospective study explores high sensitivity C-reactive protein (hs-CRP) levels in relation to dietary patterns at two time points in European children. METHODS: Out of the baseline sample of the IDEFICS study (n = 16,228), 4020 children, aged 2-9 years at baseline, with available hs-CRP levels and valid data from a food frequency questionnaire (FFQ) at baseline (T0) and 2 years later (T1) were included. K-means clustering algorithm based on the similarities between relative food consumption frequencies of the FFQ was applied. hs-CRP was dichotomized according to sex-specific cutoff points. Multilevel logistic regression was performed to assess the relationship between dietary patterns and hs-CRP adjusting for covariates. RESULTS: Three consistent dietary patterns were found at T0 and T1: 'animal protein and refined carbohydrate', 'sweet and processed' and 'healthy'. Children allocated to the 'protein' and 'sweet and processed' clusters at both time points had significantly higher odds of being in the highest category of hs-CRP (OR 1.47; 95% CI 1.03-2.09 for 'animal protein and refined carbohydrate' and OR 1.44; 95% CI 1.08-1.92 for 'sweet and processed') compared to the 'healthy' cluster. The odds remained significantly higher for the 'sweet and processed' pattern (OR 1.39; 95% CI 1.05-1.84) when covariates were included. CONCLUSIONS: A dietary pattern characterized by frequent consumption of sugar and processed products and infrequent consumption of vegetables and fruits over time was independently related with inflammation in European children. Efforts to improve the quality of the diet in childhood may prevent future diseases related with chronic inflammation.

FTO gene variation, macronutrient intake and coronary heart disease risk: a gene-diet interaction analysis.

PURPOSE: The fat mass and obesity-associated gene (FTO) is related to obesity and coronary heart disease (CHD). We studied interaction between macronutrient intake and FTO in association with CHD risk or body mass index (BMI). METHODS: The pooled population-based case-control studies, SHEEP and INTERGENE, included 1,381 first-time CHD patients and 4,290 population controls genotyped for FTO rs9939609 (T/A). Diet data were collected in self-administered food frequency questionnaires. Macronutrients were dichotomized into low/high energy percentages (E%) by median levels in controls. Association of FTO genotype (TA/AA vs. TT) with CHD risk was analysed by multiple logistic regression, and with BMI by multiple linear regression. Interaction between FTO and macronutrient was assessed by introducing an interaction term FTO × macronutrient. Interaction on CHD as deviation from additive effects was assessed by calculating relative excess risk due to interaction. RESULTS: No statistically significant interaction was found between FTO genotype and any macronutrient on CHD risk or BMI on either the multiplicative or additive scale. However, FTO genotype (TA/AA vs. TT) was associated with significantly increased CHD risk only in subjects with low E% from fat (OR 1.36, 95% CI 1.11-1.66) or saturated fatty acids (OR 1.36, 95% CI 1.10-1.69), or in subjects with high E% from carbohydrate (OR 1.32, 95% CI 1.07-1.61) or protein (OR 1.41, 95% CI 1.13-1.75). Mean BMI was 0.3-0.6 kg/m(2) higher in control subjects with TA/AA compared to TT, regardless of macronutrient E%. CONCLUSIONS: We found no evidence of interactions between FTO genotype and macronutrient intake on CHD risk or BMI.

The Mediterranean diet in relation to mortality and CVD: a Danish cohort study.

The aim of the present study was to determine whether the Mediterranean Diet Score (MDS) is associated with reduced total mortality, cardiovascular incidence and mortality in a Danish population. Analyses were performed on 1849 men and women sampled during the 1982-83 Danish MONICA (MONItoring trends and determinants of Cardiovascular disease) population study, whose diet was assessed by means of a validated 7 d food record. The adherence to a Mediterranean dietary pattern was calculated by three different scores: one based on a classification excluding ingredients from mixed dishes and recipes (score 1); another based on a classification including ingredients (score 2); the last one based on a variant of the latter including wine instead of alcohol intake (score 3). The association between these scores and, respectively, total mortality, cardiovascular incidence and mortality was tested by a Cox proportional hazards model adjusted for several potential confounders of the association. Generally, all three scores were inversely associated with the endpoints, although associations with score 1 did not reach statistical significance. Score 2 was inversely associated with total mortality (hazard ratio 0·94; 95 % CI 0·88, 0·99). This association was confirmed for total cardiovascular as well as myocardial infarction (MI) incidence and mortality, but not for stroke. Score 3 was slightly more associated with the same outcomes. All associations were also resistant to adjustment for covariates related to potential CVD pathways, such as blood lipids, blood pressure and weight change after 11 years of follow-up. In a Danish cohort, the MDS was inversely associated with total mortality and with cardiovascular and MI incidence and mortality, but not with stroke incidence or mortality.

Planning engagement with web resources to improve diet quality and break up sedentary time for home-working employees: A mixed methods study.

As home working becomes more common, employers may struggle to provide health promotion interventions that can successfully bridge the gap between employees' intentions to engage in healthier behaviors and actual action. Based on past evidence that action planning can successfully encourage the adoption of healthier behaviors, this mixed-methods study of a web-based self-help intervention incorporated a randomized planning trial that included quantitative measures of engagement and follow-up qualitative interviews with a subsample of participants. Participants either (a) selected a movement plan for incorporating a series of 2-min exercise videos into their work week to break up sedentary time and a balanced meal plan with recipe cards for a week's lunches and dinners or (b) received access to these resources without a plan. Selecting a movement plan was more effective at increasing engagement with the web resources compared to the no-plan condition. In the follow-up interviews, participants indicated that the plan helped to remind participants to engage with the resources and made it simpler for them to follow the guidance for exercises and meals. Ease of use and being able to fit exercises and meals around work tasks were key factors that facilitated uptake of the resources, while lack of time and worries about how colleagues would perceive them taking breaks to use the resources were barriers to uptake. Participants' self-efficacy was associated with general resource use but not plan adherence. Overall, including plans with online self-help resources could enhance their uptake. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Mediterranean diet score and mortality are inversely associated in adults living in the subarctic region.

The Mediterranean diet has been widely promoted and may be associated with chronic disease prevention and a better overall health status. The aim of this study was to evaluate whether the Mediterranean diet score inversely predicted total or cause-specific mortality in a prospective population study in Northern Sweden (Västerbotten Intervention Program). The analyses were performed in 77,151 participants (whose diet was measured by means of a validated FFQ) by Cox proportional hazard models adjusted for several potential confounders. The Mediterranean diet score was inversely associated with all-cause mortality in men [HR = 0.96 (95% CI = 0.93, 0.99)] and women [HR = 0.95 (95% CI = 0.91, 0.99)], although not in obese men. In men, but not in women, the score was inversely associated with total cancer mortality [HR = 0.92 (95% CI = 0.87, 0.98)], particularly for pancreas cancer [HR = 0.82 (95% CI = 0.68, 0.99)]. Cardiovascular mortality was inversely associated with diet only in women [HR = 0.90 (95% CI = 0.82, 0.99)]. Except for alcohol [HR = 0.83 (95% CI = 0.76, 0.90)] and fruit intake [HR = 0.90 (95% CI = 0.83, 0.98)], no food item of the Mediterranean diet score independently predicted mortality. Higher scores were associated with increasing age, education, and physical activity. Moreover, healthful dietary and lifestyle-related factors additively decreased the mortality likelihood. Even in a subarctic region, increasing Mediterranean diet scores were associated with a longer life, although the protective effect of diet was of small magnitude compared with other healthful dietary and lifestyle-related factors examined.

Aflatoxin B1 in imported cinnamon consumed in the Yazd province of Iran.

Aflatoxins are toxic secondary metabolites produced mainly by Aspergillus flavus and A. parasiticus, which are fungal contaminants found in several foodstuffs, including spices. In this study 40 cinnamon samples were collected in November and December 2020 in the Iranian province of Yazd and analysed for the presence of aflatoxin B1 (AFB1) by high performance liquid chromatography. Seven out of 40 (17.5%) samples were contaminated with AFB1 at levels ranging from 0.59 to 5.8 µg/kg. In addition, 2.5% of cinnamon samples contained AFB1 concentrations above the maximum level of 5 µg/kg, as established by the Iranian national standard. Due to the harmful effects of aflatoxins, even at low amounts, these can cause serious chronic health problems. Therefore, continuous control to avoid AFB1 contamination in foodstuffs is required.

Feasibility of innovative dietary assessment in epidemiological studies using the approach of combining different assessment instruments.

OBJECTIVE: To assess the feasibility of combining short-term and long-term dietary assessment instruments as new concept for improving usual dietary intake assessment on the individual level. DESIGN: Feasibility study of completing three 24 h dietary recalls (24-HDR) and a self-administered food propensity questionnaire (FPQ). The 24-HDR was conducted by monthly telephone interviews, using EPIC-SOFT software. The FPQ was completely standardized across cohorts and offered either as a web-based tool or in paper format. SETTING: Random sample derived from five ongoing European cohort studies (EPIC-San Sebastian, EPIC-Florence, EPIC-Potsdam, Estonia Genome Center (EGC) and Norwegian Women and Cancer study (NOWAC)). SUBJECTS: A total of 400 participants. RESULTS: Overall, the total participation rate for the present study was 65.3 % (n 261). On average, completion of the 24-HDR was highest for the first 24-HDR (63.0 %) and decreased slightly for the second (60.3 %) and third 24-HDR (56.3 %). The proportions of selecting the web-based FPQ varied among the study centres, with the highest in EGC (92.9 %) and NOWAC (70.0 %) and the lowest in EPIC-San Sebastian (25.5 %) and EPIC-Potsdam (33.9 %). Web users rarely requested support and were younger and more highly educated than those who completed the paper format. CONCLUSIONS: The present study supports the feasibility of a combined application of three 24-HDR and an FPQ in culturally different populations. The varying acceptance of the web-based instrument across populations requires a flexible application of assessment instruments.

Development of the Choices 5-Level Criteria to Support Multiple Food System Actions.

In 2008, the Choices International Foundation developed its logo criteria, identifying best-in-class food products. More advanced, global and graded nutrient profiling systems (NPSs) are needed to substantiate different national nutrition policies. The objective of this work was to extend Choices NPS to identify five levels of the healthiness of food products, so that the Choices NPS can also be used to support other nutrition policies, next to front-of-pack labelling. Based on the same principles as the previous logo criteria, four sets of threshold criteria were determined using a combination of compliance levels, calculated from a large international food group-specific database, the Choices logo criteria, and WHO-NPSs developed to restrict marketing to children. Validation consisted of a comparison with indicator foods from food-based dietary guidelines from various countries. Some thresholds were adjusted after the validation, e.g., because intermediate thresholds were too lenient. This resulted in a new international NPS that can be applied to different contexts and to support a variety of health policies, to prevent both undernutrition and obesity. It can efficiently evaluate mixed food products and represents a flexible tool, applicable in various settings and populations.

Multi-parametric flow cytometric cell cycle analysis using TO-PRO-3 iodide (TP3): detailed protocols.

TO-PRO-3 iodide (TP3), a monomeric cyanine nucleic acid stain with a peak absorbance at 642 nm and emission at 661 nm, is best excited by a helium-neon (HeNe) laser (633nm). It was tested in monocytes and different cell lines under conditions of different fixatives, dye concentrations, labeling kinetics and RNAse concentrations for mono-, bi- and tri-parametric flow cytometric cell cycle analysis to establish the best protocol for DNA analysis in terms of G1 peak CV, G2/G1 ratio and minimal amount of debris. A linear increase in G1 peak position was found from 0.1 to 2 microM TP3 concentrations. Fixatives 70% ethanol or 1% methanol-free formaldehyde, followed by 70% ethanol, resulted in the best DNA histograms. Although different protocols were found to be cell-type specific, in general, excellent results were obtained with 30 min incubation with 0.5 microM TP3 plus RNAse in almost all cell lines tested. These data show that TP3 is an alternative method to propidium iodide (PI), the most commonly used DNA-specific probe in flow cytometry. The most important advantage of using TP3 in combination with other fluorochromes, such as fluorescein isothiocyanate (FITC) or phycoerythrin (PE) in bi- or tri-parametric flow cytometric analysis, is that there is no need for fluorescence compensation for the TP3 signals.

Nonfermented milk and other dairy products: associations with all-cause mortality.

Background: A positive association between nonfermented milk intake and increased all-cause mortality was recently reported, but overall, the association between dairy intake and mortality is inconclusive.Objective: We studied associations between intake of dairy products and all-cause mortality with an emphasis on nonfermented milk and fat content.Design: A total of 103,256 adult participants (women: 51.0%) from Northern Sweden were included (7121 deaths; mean follow-up: 13.7 y). Associations between all-cause mortality and reported intakes of nonfermented milk (total or by fat content), fermented milk, cheese, and butter were tested with the use of Cox proportional hazards models that were adjusted for age, sex, body mass index, smoking status, education, energy intake, examination year, and physical activity. To circumvent confounding, Mendelian randomization was applied in a subsample via the lactase LCT-13910 C/T single nucleotide polymorphism that is associated with lactose tolerance and milk intake.Results: High consumers of nonfermented milk (≥2.5 times/d) had a 32% increased hazard (HR: 1.32; 95% CI: 1.18, 1.48) for all-cause mortality compared with that of subjects who consumed milk ≤1 time/wk. The corresponding value for butter was 11% (HR: 1.11; 95% CI: 1.07, 1.21). All nonfermented milk-fat types were independently associated with increased HRs, but compared with full-fat milk, HRs were lower in consumers of medium- and low-fat milk. Fermented milk intake (HR: 0.90; 95% CI: 0.86, 0.94) and cheese intake (HR: 0.93; 95% CI: 0.91, 0.96) were negatively associated with mortality. Results were slightly attenuated by lifestyle adjustments but were robust in sensitivity analyses. Mortality was not significantly associated with the LCT-13910 C/T genotype in the smaller subsample. The amount and type of milk intake was associated with lifestyle variables.Conclusions: In the present Swedish cohort study, intakes of nonfermented milk and butter are associated with higher all-cause mortality, and fermented milk and cheese intakes are associated with lower all-cause mortality. Residual confounding by lifestyle cannot be excluded, and Mendelian randomization needs to be examined in a larger sample.

Induction of resistance to Aplidin in a human ovarian cancer cell line related to MDR expression.

Aplidin-resistant IGROV-1/APL cells were derived from the human ovarian cancer IGROV-1 cell line by exposing the cells to increasing concentration of Aplidin for eight months, starting from a concentration of 10 nM to a final concentration of 4 microM. IGROV-1/APL cell line possesses five fold relative resistance to Aplidin. IGROV-1/APL resistant cell line shows the typical MDR phenotype: (1) increased expression of membrane-associated P-glycoprotein, (2) cross-resistance to drugs like etoposide, doxorubicin, vinblastine, vincristine, taxol, colchicin and the novel anticancer drug Yondelis (ET-743). The Pgp inhibitor cyclosporin-A restored the sensitivity of IGROV-1/APL cells to Aplidin by increasing the drug intracellular concentration. The resistance to Aplidin was not due to the other proteins, such as LPR-1 and MRP-1, being expressed at the same level in resistant and parental cell line. The finding that cells over-expressing Pgp are resistant to Aplidin was confirmed in CEM/VLB 100 cells, that was found to be 5-fold resistant to Aplidin compared to the CEM parental cell line.

Are segmental MF-BIA scales able to reliably assess fat mass and lean soft tissue in an elderly Swedish population?

BACKGROUND AND AIMS: The assessment of body composition is an important measure to monitor the process of healthy aging and detect early signs of disease. Dual X-ray absorptiometry (DXA) is considered a valid technique for the assessment of body composition but is confined to the clinical environment. Multi-frequency bio-electrical impedance analysis (MF-BIA) might be a versatile alternative to DXA. We aimed to assess whether a segmental MF-BIA scale can be an accurate and reliable tool for the monitoring of body composition in the elderly and whether the presence of metallic prostheses can influence the agreement between the two techniques. SUBJECTS AND METHODS: Weight and height were measured in 92 healthy subjects (53 women) aged 80-81 years from the H70 Gerontological and Geriatric study in Gothenburg. Total and segmental fat mass (FM) and lean soft tissue (LST) were estimated by DXA (Lunar Prodigy, Scanex, Sweden) and segmental MF-BIA (MC-180MA, Tanita, Japan). Bland-Altman analyses were performed to assess the agreement between the two techniques. The prediction of DXA-FM by MF-BIA was compared to that of the body mass index (BMI). RESULTS AND DISCUSSION: MF-BIA showed a significant underestimation of FM and an overestimation of LST that was larger in men than in women. Smaller but significant deviations were found for appendicular LST and SMM. MF-BIA was not superior to BMI at predicting DXA-FM. The lack of agreement between MF-BIA and DXA was not due to the presence of metal prostheses or diagnoses such as hypertension and edema. The prediction equations applied by the device used in this study should be adapted to the elderly population and details about the reference population(s) should be disclosed.

Comparison of apolipoprotein (apoB/apoA-I) and lipoprotein (total cholesterol/HDL) ratio determinants. Focus on obesity, diet and alcohol intake.

The ratio between apolipoprotein B and apolipoprotein A-I (apoB/apoA-I) has been suggested to be a powerful and more accurate predictor of future cardiovascular disease risk than total cholesterol and HDL cholesterol. Since diet and lifestyle can directly influence dyslipidemia, it is of interest to identify modifiable factors that are associated with high levels of the apolipoprotein ratio and if they can have a different association with a more traditional indicator of cardiovascular risk such as total cholesterol/HDL. The relationship between obesity and dyslipidemia is established and it is of interest to determine which factors can modify this association. This study investigated the cross-sectional association of obesity, diet and lifestyle factors with apoB/apoA-I and total cholesterol/HDL respectively, in a Swedish population of 2,907 subjects (1,537 women) as part of the INTERGENE study. The apolipoprotein and lipoprotein ratios were highly correlated, particularly in women, and obesity was strongly associated with both. Additionally, age, cigarette smoking and alcohol intake were important determinants of these ratios. Alcohol was the only dietary factor that appreciably attenuated the association between obesity and each of the ratios, with a stronger attenuation in women. Other dietary intake and lifestyle-related factors such as smoking status and physical activity had a lower effect on this association. Because the apolipoprotein and lipoprotein ratios share similar diet and lifestyle determinants as well as being highly correlated, we conclude that either of these ratios may be a sufficient indicator of dyslipidemia.

Does the Mediterranean diet predict longevity in the elderly? A Swedish perspective.

Dietary pattern analysis represents a useful improvement in the investigation of diet and health relationships. Particularly, the Mediterranean diet pattern has been associated with reduced mortality risk in several studies involving both younger and elderly population groups. In this research, relationships between dietary macronutrient composition, as well as the Mediterranean diet, and total mortality were assessed in 1,037 seventy-year-old subjects (540 females) information. Diet macronutrient composition was not associated with mortality, while a refined version of the modified Mediterranean diet index showed a significant inverse association (HR=0.93, 95% CI: 0.89; 0.98). As expected, inactive subjects, smokers and those with a higher waist circumference had a higher mortality, while a reduced risk characterized married and more educated people. Sensitivity analyses (which confirmed our results) consisted of: exclusion of one food group at a time in the Mediterranean diet index, exclusion of early deaths, censoring at fixed follow-up time, adjusting for activities of daily living and main cardiovascular risk factors including weight/waist circumference changes at follow up. In conclusion, we can reasonably state that a higher adherence to a Mediterranean diet pattern, especially by consuming wholegrain cereals, foods rich in polyunsaturated fatty acids, and a limited amount of alcohol, predicts increased longevity in the elderly.

Fruit and vegetable intakes and subsequent changes in body weight in European populations: results from the project on Diet, Obesity, and Genes (DiOGenes).

BACKGROUND: High fruit and vegetable intakes may limit weight gain, particularly in susceptible persons, such as those who stop smoking. OBJECTIVE: The objective was to assess the association of fruit and vegetable intake with subsequent weight change in a large-scale prospective study. DESIGN: The data used were from 89,432 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). The association between fruit and vegetable intake and weight change after a mean follow-up of 6.5 y was assessed by linear regression. Polytomous logistic regression was used to evaluate whether fruit and vegetable intake relates to weight gain, weight loss, or both. RESULTS: Per 100-g intake of fruit and vegetables, weight change was -14 g/y (95% CI: -19, -9 g/y). In those who stopped smoking during follow-up, this value was -37 g/y (95% CI: -58, -15 g/y; P for interaction < 0.0001). When weight gain and loss were analyzed separately per 100-g intake of fruit and vegetables in a combined model, the odds ratios (95% CIs) were 0.97 (0.95, 0.98) for weight gain > or =0.5 and <1 kg/y, 0.94 (0.92, 0.96) for weight gain > or =1 kg/y, and 0.97 (0.95, 0.99) for weight loss > or =0.5 kg/y. In those who stopped smoking during follow-up, the odds ratios (95% CIs) were 0.93 (0.88, 0.99), 0.87 (0.81, 0.92), and 0.97 (0.88, 1.07), respectively (P for interaction < 0.0001). CONCLUSIONS: Fruit and vegetable intake relates significantly, albeit weakly inversely, to weight change. For persons who stop smoking, high fruit and vegetable intakes may be recommended to reduce the risk of weight gain.

Multiple effects of paclitaxel are modulated by a high c-myc amplification level.

Paclitaxel affects microtubule stability by binding to beta-tubulin, thus leading to cell accumulation in the G(2)/M phase, polyploidization, and apoptosis. Because both cell proliferation and apoptosis could be somehow regulated by the protooncogene c-myc, in this work we have investigated whether the c-myc amplification level could modulate the multiple effects of paclitaxel. To this aim, paclitaxel was administered to SW613-12A1 and -B3 human colon carcinoma cell lines (which are characterized by a high and low c-myc endogenous amplification level, respectively), and to the B3mycC5 cell line, with an enforced exogenous expression of c-myc copies. In this experimental system, we previously demonstrated that a high endogenous/exogenous level of amplification of c-myc enhances serum deprivation- and DNA damage-induced apoptosis. Accordingly, the present results indicate that a high c-myc amplification level potentiates paclitaxel cytotoxicity, confers a multinucleated phenotype, and promotes apoptosis to a great extent, thus suggesting that c-myc expression level is relevant in modulating the cellular responses to paclitaxel. We have recently shown in HeLa cells that the phosphorylated form of c-Myc accumulates in the nucleus, as distinct nucleolar and extranucleolar spots; here, we demonstrated that, after the treatment with paclitaxel, phosphorylated c-Myc undergoes redistribution, becoming diffused in the nucleoplasm.

Unique features of the mode of action of ET-743.

This paper describes the current knowledge of the primary mode of action of a natural product, ecteinascidin 743 (ET-743), derived from the marine tunicate Ecteinascidia turbinata. ET-743 was initially selected for preclinical development because of its potent antitumor activity observed against several human solid tumor types. In vitro, the drug is cytotoxic in the nanomolar range, and in the case of some very sensitive cell lines, in the picomolar range. The large potency differences observed among several solid tumor types indicate that this compound possesses some tumor selectivity, but the molecular basis of these differential effects remains to be elucidated. The present studies were undertaken to evaluate the mechanism of action of ET-743 in this context. The available information on ET-743 binding to DNA and its effects on transcriptional regulation point to a unique behavior of this drug, as it independently affects specific gene transcription in a promoter-dependent way. In addition, ET-743 shows a peculiar pattern of selectivity in cells with different defects in their DNA-repair pathways. These results highlight a unique property of ET-743, possibly explaining why it possesses antitumor activity against tumors that are refractory to standard anticancer drugs, all of which certainly act by mechanisms that are different from that of ET-743.