Medical Bulletin 13/July/2023

Advancements in treating chemotherapy-resistant prostate cancer

Researchers reporting in ACS Central Science have developed the first therapy of its kind that disrupts prostate cancer cells’ metabolism and releases cisplatin into the weakened cells, causing them to die. In mouse models, an orally administered version shrunk tumors substantially. Researchers from Sylvester Comprehensive Cancer Center at the University of Miami wanted to develop a therapy that would inhibit fatty acid oxidation in cancer cells by targeting a mitochondrial protein that is vital to the metabolic process, making the cells susceptible to cisplatin.

The researchers verified that human prostate cancer cells thrive using fatty acid oxidation by assessing the biopsies of 38 people with the disease. The cisplatin prodrug Platin-L, which has a cisplatin molecule bound to a 12-carbon fatty acid on one side and succinate on the other side, had the greatest effect by binding to a key protein required for long-chain fatty acid transport, a primary step in this metabolic process. And in trials, Platin-L reduced the growth of prostate cancer cells by over 50% in several different cell lines.

Reference: New Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance, ACS Central Science, DOI 10.1021/acscentsci.3c00286

Blood pressure patterns in early pregnancy predicted preeclampsia and gestational hypertension better

Routine blood pressure readings recorded in the first half of pregnancy can be divided into 6 distinct patterns that can effectively stratify patients by their risk of developing preeclampsia and gestational hypertension later in pregnancy, Kaiser Permanente researchers found.

The study showed that 6 pregnancy blood pressure trajectories seen within the first 20 weeks of pregnancy along with clinical, social, and behavioral risk factors can accurately predict and stratify1(remove “vs” in image) risk of preeclampsia and gestational hypertension in low- to moderate-risk patients. Three of the early pregnancy blood pressure trajectories identified 74% of the patients who went on to develop preeclampsia later in their pregnancy. The prediction model worked equally well in the white, Black, Hispanic, and Asian patients included in the study.

Reference: Early Pregnancy Systolic Blood Pressure Patterns Predict Early- and Later-onset Preeclampsia and Gestational Hypertension Among Ostensibly Low-to-Moderate Risk Groups, Journal of the American Heart Association

Gut bacteria linked to heart artery fat deposits

In a major Swedish study, researchers have discovered a link between the levels of certain bacteria living in the gut and coronary atherosclerotic plaques. Such atherosclerotic plaques, which are formed by the build-up of fatty and cholesterol deposits, constitute a major cause of heart attacks. The study was led by researchers at Uppsala and Lund University.

The new study was based on analyses of gut bacteria and cardiac imaging among 8,973 participants aged 50 to 65 from Uppsala and Malmö without previously known heart disease.

Reference: Streptococcus species abundance in the gut is linked to subclinical coronary atherosclerosis in 8 973 participants from the SCAPIS cohort, Circulation, DOI 10.1161/CIRCULATIONAHA.063914DR2