| 1. |
- Handl, Verena, et al.
(författare)
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Continuous iontronic chemotherapy reduces brain tumor growth in embryonic avian in vivo models
- 2024
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Ingår i: Journal of Controlled Release. - : ELSEVIER. - 0168-3659 .- 1873-4995. ; 369, s. 668-683
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Tidskriftsartikel (refereegranskat)abstract
- Local and long-lasting administration of potent chemotherapeutics is a promising therapeutic intervention to increase the efficiency of chemotherapy of hard-to-treat tumors such as the most lethal brain tumors, glioblastomas (GBM). However, despite high toxicity for GBM cells, potent chemotherapeutics such as gemcitabine (Gem) cannot be widely implemented as they do not efficiently cross the blood brain barrier (BBB). As an alternative method for continuous administration of Gem, we here operate freestanding iontronic pumps - "GemIPs" - equipped with a custom-synthesized ion exchange membrane (IEM) to treat a GBM tumor in an avian embryonic in vivo system. We compare GemIP treatment effects with a topical metronomic treatment and observe that a remarkable growth inhibition was only achieved with steady dosing via GemIPs. Daily topical drug administration (at the maximum dosage that was not lethal for the embryonic host organism) did not decrease tumor sizes, while both treatment regimes caused S-phase cell cycle arrest and apoptosis. We hypothesize that the pharmacodynamic effects generate different intratumoral drug concentration profiles for each technique, which causes this difference in outcome. We created a digital model of the experiment, which proposes a fast decay in the local drug concentration for the topical daily treatment, but a long-lasting high local concentration of Gem close to the tumor area with GemIPs. Continuous chemotherapy with iontronic devices opens new possibilities in cancer treatment: the long-lasting and highly local dosing of clinically available, potent chemotherapeutics to greatly enhance treatment efficiency without systemic side-effects. Significance statement: Iontronic pumps (GemIPs) provide continuous and localized administration of the chemotherapeutic gemcitabine (Gem) for treating glioblastoma in vivo. By generating high and constant drug concentrations near the vascularized growing tumor, GemIPs offer an efficient and less harmful alternative to systemic administration. Continuous GemIP dosing resulted in remarkable growth inhibition, superior to daily topical Gem application at higher doses. Our digital modelling shows the advantages of iontronic chemotherapy in overcoming limitations of burst release and transient concentration profiles, and providing precise control over dosing profiles and local distribution. This technology holds promise for future implants, could revolutionize treatment strategies, and offers a new platform for studying the influence of timing and dosing dependencies of already -established drugs in the fight against hard -to -treat tumors.
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| 2. |
- Saarela, Jan, et al.
(författare)
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Ethnic Composition of Couples and Mutual Health Benefit Receipt : Register-Based Evidence from Finland
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- The literature on health dependencies among partners typically ignores diversity of partnership characteristics. One salient example is the ethnic composition. We extend prior work on partnerships and health by investigating how married and cohabiting partners mutually influence each other’s receipt of health-related benefits, focusing on how such correlations vary with the couple’s ethnic composition. We study partners’ mutual receipt of sickness allowance and disability pension in ethnically endogamous and exogamous couples in Finland. The population consists of native individuals in similar socioeconomic positions but belonging to two different ethnic groups—Finnish and Swedish speakers—who differ in health and family life. Using data from population registers, we estimate discrete-time hazard models for first-time benefit receipt, as related to partner’s benefit receipt, among midlife couples. We found evidence of mutual receipt of health benefits in both endogamous and exogamous couples, the correlation being strongest for disability pension. Partner correlation in disability pension receipt is slightly stronger in endogamous Swedish than in endogamous Finnish couples, while women in exogamous couples are slightly less sensitive to men’s receipt than vice versa. The results show that mutual health may be heterogeneous across couples that differ in ethnic composition.
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| 3. |
- Saarela, Jan, et al.
(författare)
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Ethnic Composition of Couples and Mutual Health Benefit Receipt: Register-Based Evidence from Finland
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We study partners’ mutual receipt of sickness allowance and disability pension in ethnically endogamous and exogamous couples in Finland. The population consists of native individuals in similar socioeconomic positions but belonging to two different ethnic groups, Finnish and Swedish speakers, which differ regarding health and cultural practices related to family life. Using data from population registers (1987-2011, n = 36,034 couples), we estimate discrete-time hazard models for first-time benefit receipt related to partner’s benefit receipt amongmidlife couples. We find evidence of mutual receipt of health benefits in both endogamous and exogamous couples, the correlation being strongest for disability pension. Partner correlation in disability pension receipt is slightly stronger in endogamous Swedish than in endogamous Finnish couples, while women in exogamous couples are slightly less sensitive to men’s receipt than vice versa. These findings show that the ethnic composition of couples is important for mutual health benefit receipt.
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