Medium GDF-15 reduces vomiting, anorexia, and body weight caused by platinum chemicals...

Platinum is the world's most widely used drug for cancer treatment, known as cisplatin, carabenium and oxalipari.
However, the use of platinum drugs has been limited by adverse reactions after their use, including nausea and vomiting, anorexia, weight loss, etc., the presence of these side effects reduce the quality of life of patients and treatment compliance.
although platinum drugs have been used clinically for nearly 50 years, little is known about the mechanisms by which they produce adverse reactions.
recent years, it has been reported that growth differentiation factor GDF-15 can trigger adverse reactions such as anorexia and weight loss in animal models, and platinum drugs have been shown to increase GDF-15 levels in the circulation of testicular cancer patients.
GDF-15 is selectively expressed in the last region of the brain (area postrema, AP) and solitary nuclei (nucleus of the solitary tract, NTS) and adjusts the energy balance by activating the receptor sample of neuroglial cell-derived neurotrophic factor receptor alpha-like, GFRAL).
Previous studies have also shown that increasing GDF-15 increases the expression of c-Fos in the back brain (AP and NTS), armside and amygdala, and these brain regions are critical to regulating anorexia behavior under stress conditions, suggesting a possible link between cisplatin and GDF-15.
November 17, 2020, the Danna M. Breen research team of Pfizer published an online article in Cell-Metabolism entitled "GDF-15 Neutralization Alleviates Platinum-Based Process-Induced Emesis, Anorexia, Weight and Loss in Mice and Nonhuman Primates."
they found that in mice and non-human primates, the growth differentiation factor 15 (GDF-15) reduced vomiting, anorexia and weight loss caused by platinum chemicals.
DOI: The team first tested serum GDF-15 levels in cancer patients with non-small cell lung cancer (NSCLC), colorectal and ovarian cancer, and received platinum or non-platinum chemotherapy.
results showed higher levels of GDF-15 in circulatory blood in patients with NSCLC, colorectal and ovarian cancer than in the healthy control group, higher levels of GDF-15 in subjects receiving platinum chemotherapy than in non-platinum chemotherapy, and higher levels of circulating GDF-15 were also significantly associated with weight loss in patients.
, the team used a series of experiments to explore the dependence of GDF-15 on side effects such as cisplatin-induced anorexia and weight loss.
results showed that after the use of cisplatin in wild and GDF-15-knocked mice, the plasma GDF-15 level increased within 8 hours of cisplatin treatment in wild mice, and no abnormalities of any other circulating inflammatory proteins, such as IFN-γ, TNF-α, IL-2, etc., were detected during this period.
also showed significant weight loss after cisplatin therapy in wild mice, and the symptoms were significantly alleviated in mice that were knocked out by GDF-15.
addition, anorexia caused by cisplatin was not observed in mice knocked out by GDF-15.
experimental flowchart mAB1 is a monoclonal antibody resistant to human GDF-15 that neutrals GDF-15 in circulation, thus preventing its binding to GFRAL subjects and having a high level of cross-reactivity to non-human primates and mice GDF-15.
, the researchers tried to prove the meso-15 effect of mAB1 on GDF-15 using human GDF-15 over-expression models.
results showed that wild mice infected with the recombined GDF-15 gland-related virus had elevated GDF-15 levels and significant weight loss in mice compared to the control group, while mice were given mAB1 and IgG treatment, respectively, which can quickly cause weight gain.
mAB1 treatment in mice not infected with the recombined GDF-15 gland-related virus did not cause weight changes.
, the researchers also used non-human primates to eat crab monkeys.
results were consistent with the prediction, and the occurrence of vomiting was significantly reduced by mAB1 to medium and circulate GDF-15 in blood.
And the researchers also demonstrated that using mAB1 and GDF-15 reduced the weight loss of cisplatin-induced non-small cell lung cancer lotus mice without affecting the effects of cisplatin itself on tumor growth and improved survival.
In summary, this article explores the effects of GDF-15 on vomiting, anorexia and weight loss in mice and/or non-human primates caused by platinum chemotherapy, and finds that meso-GDF-15 is a potential treatment that can reduce the side effects of chemotherapy and improve the quality of life of patients.
: gDF-15 Neutralization Alleviates Platinum-Based Processy-Induced Emesis, Anorexia, and Weight Ross in Mice and Nonhuman Primates.