| 1. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 2. |
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| 3. |
- Axmon, Anna, et al.
(författare)
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Female fertility in relation to the consumption of fish contaminated with persistent organochlorine compounds.
- 2002
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 28:2, s. 124-132
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The purpose of the study was to assess the effect of exposure to presistent organochlorine compounds through the consumption of fatty fish from the Baltic Sea on human fertility. METHODS: Information on time to pregnancy, miscarriages, and subfertility was collected retrospectively by self-administered questionnaires in two cohorts of fishermen's sisters from the Swedish east coast, by the Baltic Sea, and the west coast, where fish are less contaminated. Along with cohort affiliation, fish consumption and growing up in a fishing village or fisherman's family were used as measures of exposure within the eastcoast cohort (ie, the exposed cohort). RESULTS: There was no support for a negative effect of the consumption of fatty Baltic Sea fish on time to pregnancy, miscarriages, or subfertility. On the contrary, some evidence pointed towards a protective effect of fatty fish consumption within both cohorts. CONCLUSIONS: No evidence of reduced fertility was found for women who could be assumed to have a high lifetime consumption of fatty fish contaminated by persistent organochlorine compounds. A possible explanation for this finding is that a positive effect of some of the constituents in fatty fish could be strong enough to disguise the hazardous effects of exposure to persistent organochlorine compounds.
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| 4. |
- Axmon, Anna, et al.
(författare)
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Polychlorinated biphenyls in blood plasma among Swedish female fish consumers in relation to time to pregnancy
- 2001
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Ingår i: Journal of Toxicology and Environmental Health. Part A: Current Issues. - : Informa UK Limited. - 1087-2620 .- 1528-7394. ; 64:6, s. 485-498
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to assess the association between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma, a biomarker of exposure to polychlorinated biphenyls (PCB), and time to pregnancy (TTP) in a group of women with a varying dietary exposure to PCB. For 121 Swedish east coast fishermen's wives (median year of birth 1956, range 1945-1968), information on selt-reported TTP for the first planned pregnancy (median 2 mo, range 0-48) and CB-153 concentrations from blood samples drawn in 1995 (median 144 ng/g lipid, range 16-566) were available. Each woman's CB-153 concentration in plasma at the time immediately preceding her pregnancy was estimated, taking into account reduction of body burden of CB-153 due to lactation, the yearly reduction of PCB in Baltic Sea fish, as well as the biological half-life of CB-153. Based on the estimated CB-153 concentrations, subjects were categorized into tertiles as low (37-206 ng/g lipid), medium (207-330 ng/g lipid), and high (331-,1036 ng/g lipid) exposure groups. TTP in the medium- and high-exposure groups were then compared to TTP in the low-exposure group by estimating the corresponding success rate (i.e., the number of pregnancies per person month) ratios (SuRR) using discrete Cox regression, taking into account essential confounders. No obvious association between estimated CB-153 concentration and TTP was observed (medium vs. low: SuRR 0.77 [95% CI 0.47-1.28] and high vs. low: SuRR 0.95 10.74-1.23]). The present data give no support for a negative association between the plasma CB-153 concentrations observed in the present study and TTP. It should, however, be borne in mind that the study group was rather small and mainly included relatively young women, likely to have been only moderately exposed.
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| 5. |
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| 6. |
- Beiron, Johanna, 1992, et al.
(författare)
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Enhancement of CO2 Absorption in Water through pH Control and Carbonic Anhydrase - A Technical Assessment
- 2019
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Ingår i: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 1520-5045 .- 0888-5885. ; 58:31, s. 14275-14283
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Tidskriftsartikel (refereegranskat)abstract
- This paper provides an industrial-scale technical assessment of absorption of CO2 in water to react into bicarbonate (HCO3−), with the goal of storing HCO3− in the oceans as a carbon sequestration technology. A potential advantage of the process is that it will not require a CO2 transport and storage infrastructure that will be expensive for small-scale and remote emission sources. Process simulations are utilized to estimate absorber column length and for mass flow estimations of water and base required for a target capture rate of 90%. The results indicate that the process is technically feasible under specific conditions, with pH regulation being highly important, although the demand for base represents a limiting factor. Yet, a potential niche for the process is CO2 capture at smaller plants emitting small amounts of CO2.
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| 7. |
- Rylander, Lars, et al.
(författare)
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Polychlorinated biphenyls in blood plasma among Swedish female fish consumers in relation to low birth weight
- 1998
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Ingår i: American Journal of Epidemiology. - 0002-9262. ; 147:5, s. 493-502
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Tidskriftsartikel (refereegranskat)abstract
- The authors examined the hypothesized association between the body burden of polychlorinated biphenyls (PCB) in women and the risk of low birth weight for their infants. In Sweden, a main exposure route for PCBs and other persistent organochlorine compounds is through the consumption of fatty fish from the Baltic Sea (on the Swedish east coast). A previous comparison between a cohort of consumers of large quantities of fish from the Swedish east coast and a reference population, together with a following analysis based on questionnaire data from a case-control study within the east coast cohort, supported the hypothesized association. In 1995, blood samples were collected from the wives and ex-wives of fishermen from the Swedish east coast (n = 192) who had given birth during the period 1973-1991. Cases (n = 57), i.e., infants with low birth weight (1,500-2,750 g), were matched with controls (n = 135; birth weight, 3,250-4,500 g) on gender, parity, and calendar year of birth. The concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma was analyzed; it has been suggested that CB-153 is a relevant biomarker of exposure to PCBs. The concentration of CB-153 in the plasma of mothers during the year of childbirth was "estimated" using some alternative plausible kinetic models. For two alternative estimated exposure datasets, which were focused on separately, an increase in the risk of a low birth weight was observed at a CB-153 concentration of 300 and 400 ng/g lipid weight, respectively (adjusted odds ratios of 2.1 (95% confidence interval (CI) 1.0-4.7) and 2.3 (95% CI 0.9-5.9)). The present results strengthen the findings reported previously for this study population.
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| 8. |
- Rylander, Lars, et al.
(författare)
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Weight and height at 4 and 7 years of age in children born to mothers with a high intake of fish contaminated with persistent organochlorine pollutants.
- 2007
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Ingår i: Chemosphere. - : Elsevier BV. - 1879-1298 .- 0045-6535. ; 67:3, s. 498-504
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Tidskriftsartikel (refereegranskat)abstract
- In Sweden the main exposure route for persistent organochlorine pollutants (POP) is through consumption of fatty fish from the Baltic Sea (off the eastern coast). The present study aimed to investigate whether intrauterine exposure for POP may have negative impact on children's weight and height at 4 and 7 years of age, respectively. The study included 174 fishermen's wives from the Swedish east coast who had given birth to an infant with either low (n = 55) or normal (n = 119) birth weight, and 88 and 206 corresponding women from the Swedish west coast (where the fish is less polluted). Comparisons between the east and west coast cohorts were performed. In addition, blood samples were collected among the cast coast women and the concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma was analyzed and estimated for the year of childbirth. There were no significant differences between the east and west coast cohorts regarding weight and height at 4 and 7 years of age. There were, however, significant negative associations between the estimated plasma concentrations of CB-153 during year of childbirth and weight at 4 and 7 years of age, respectively, among the normal birth weight children. The study gives only very weak support for the hypothesized association.
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| 9. |
- Strömberg, Ulf, 1964, et al.
(författare)
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Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: An analysis of health equity based on a randomised trial
- 2022
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Ingår i: eClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 47
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have addressed health equity attained by fecal immunochemical testing (FIT) and primary colonoscopy (PCOL), respectively, in the randomised controlled screening trial SCREESCO conducted in Sweden. Methods: We analysed data on the individuals recruited between March 2014, and March 2020, within the study registered with ClinicalTrials.gov, NCT02078804. Swedish population registry data on educational level, household income, country of birth, and marital status were linked to each 60-year-old man and woman who had been randomised to two rounds of FIT 2 years apart (n = 60,123) or once-only PCOL (n = 30,390). Furthermore, we geo-coded each study individual to his/her residential area and assessed neighbourhood-level data on deprivation, proportion of non-Western immigrants, population density, and average distance to healthcare center for colonoscopy. We estimated adjusted associations of each covariate with the colonoscopy attendance proportion out of all invited to respective arms; ie, the preferred outcome for addressing health equity. In the FIT arm, the test uptake and the colonoscopy uptake among the test positives were considered as the secondary outcomes. Findings: We found a marked socioeconomic gradient in the colonoscopy attendance proportion in the PCOL arm (adjusted odds ratio [95% credibility interval] between the groups categorised in the highest vs. lowest national quartile for household income: 2·20 [2·01–2·42]) in parallel with the gradient in the test uptake of the FIT × 2 screening (2·08 [1·96–2·20]). The corresponding gradient in the colonoscopy attendance proportion out of all invited to FIT was less pronounced (1·29 [1·16–1·42]), due to higher proportions of FIT positives in socioeconomically disadvantaged groups. Interpretation: The unintended risk of exacerbating inequalities in health by organised colorectal cancer screening may be higher with a PCOL strategy than a FIT strategy, despite parallel socioeconomic gradients in uptake. Funding: This work was supported by the Swedish Cancer Society under Grant 20 0719. CB and US provided economic support from the Swedish Research Council for Health, Working life, and Welfare under Grant 2020–00962.
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| 10. |
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