Browsing by Author "Van Jaarsveld, Paul J."

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    Chemoresistance : intricate interplay between breast tumor cells and adipocytes in the tumor microenvironment
    (Frontiers Media, 2018-12-11) Mentoor, Ilze; Engelbrecht, Anna-Mart; Van Jaarsveld, Paul J.; Nell, Theo A.; Vella, Veronica
    Excess adipose tissue is a hallmark of an overweight and/or obese state as well as a primary risk factor for breast cancer development and progression. In an overweight/obese state adipose tissue becomes dysfunctional due to rapid hypertrophy, hyperplasia, and immune cell infiltration which is associated with sustained low-grade inflammation originating from dysfunctional adipokine synthesis. Evidence also supports the role of excess adipose tissue (overweight/obesity) as a casual factor for the development of chemotherapeutic drug resistance. Obesity-mediated effects/modifications may contribute to chemotherapeutic drug resistance by altering drug pharmacokinetics, inducing chronic inflammation, as well as altering tumor-associated adipocyte adipokine secretion. Adipocytes in the breast tumor microenvironment enhance breast tumor cell survival and decrease the efficacy of chemotherapeutic agents, resulting in chemotherapeutic resistance. A well-know chemotherapeutic agent, doxorubicin, has shown to negatively impact adipose tissue homeostasis, affecting adipose tissue/adipocyte functionality and storage. Here, it is implied that doxorubicin disrupts adipose tissue homeostasis affecting the functionality of adipose tissue/adipocytes. Although evidence on the effects of doxorubicin on adipose tissue/adipocytes under obesogenic conditions are lacking, this narrative review explores the potential role of obesity in breast cancer progression and treatment resistance with inflammation as an underlying mechanism.
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    Decreased efficacy of doxorubicin corresponds with modifications in lipid metabolism markers and fatty acid profiles in breast tumors from obese vs. lean mice
    (Frontiers Media, 2018-03-17) Mentoor, Ilze; Nell, Theo A.; Emjedi, Zaakiyah; Van Jaarsveld, Paul J.; De Jager, Louis; Engelbrecht, Anna-Mart; Sotgia, Federica
    Breast cancer cells modulate lipid and fatty acid metabolism to sustain proliferation. The role of adipocytes in cancer treatment efficacy remains, however, to be fully elucidated. We investigated whether diet-induced obesity (DIO) affects the efficacy of doxorubicin treatment in a breast tumor-bearing mouse model. Female C57BL6 mice were fed a high fat or low fat diet for the full duration of the study (12 weeks). After 8 weeks, mice were inoculated with E0771 triple-negative breast cancer cells in the fourth mammary gland to develop breast tumor allographs. Tumor-bearing mice received either vehicle (Hank's balanced salt solution) or doxorubicin (chemotherapy). Plasma inflammatory markers, tumor, and mammary adipose tissue fatty acid composition, as well as protein expression of lipid metabolism markers were determined. The high fat diet (HFD) attenuated the treatment efficacy of doxorubicin. Both leptin and resistin concentrations were significantly increased in the HFD group treated with doxorubicin. Suppressed lipogenesis (decreased stearoyl CoA-desaturase-1) and lipolysis (decreased hormone-sensitive lipase) were observed in mammary adipose tissue of the DIO animals, whereas increased expression was observed in the tumor tissue of doxorubicin treated HFD mice. Obesogenic conditions induced altered tissue fatty acid (FA) compositions, which reduced doxorubicin's treatment efficacy. In mammary adipose tissue breast cancer cells suppressed the storage of FAs, thereby increasing the availability of free FAs and favored inflammation under obesogenic conditions.