Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression.

P2Y receptors, including eight subtypes, are G protein-coupled receptors that can be activated by extracellular nucleotides. Nearly all P2Y receptors are expressed in bone cells, suggesting their involvements in bone physiology and pathology. However, their exact roles in bone homeostasis are not entirely clear. Therefore, this mini review summarizes new research developments regarding individual P2Y receptors and their roles in bone biology, particularly detailing those which execute both anabolic and catabolic functions. This dual function has highlighted the conundrum of pharmacologically targeting these P2Y receptors in bone-wasting diseases. Further research in finding more precise targeting strategy, such as promoting anabolic effects via combining with physical exercise, should be prioritized.

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression.

Background: Prostate cancer (PCa) preferentially metastasizes to bone, causing considerable mortality and morbidity. Exercise is a widely accepted intervention for improving bone health and can benefit overall health in patients with PCa. However, there are no direct studies defining the impact of various exercise regimens on the development of PCa bone metastasis. Hypothesis: Exercise regimens that induce osteogenic responses inhibit the growth of PCa cells in bone. Methods: Human PCa cells (PC3, 1x105 cells per injection) were intracardiacally injected into 8-week-old male BALB/c nude mice which were then subjected to right tibial dynamic mechanical loading (mimicking load bearing exercise, 9N peak force, 40 cycles with 10 second intervals, three times a week) or treadmill exercise (12 meters/minute, 30 minutes/day, 5 days/week) for 3 weeks. Another cohort of mice were firstly subjected to one week of mechanical loading before the inoculation of PC3 cells and then withdrawn from exercise regimen. The growth of skeletal tumours was tracked by bioluminescence for 3 weeks post-injection and bone structure was examined by micro-CT ex vivo. For mechanical loading experiments, comparison was made between loaded and contra-lateral non-loaded tibias, while treadmill exercise group was compared to sedentary controls in the treadmill study. Results: In the continuous mechanical loading group, tumours were detected in non-loaded tibias in all 12 mice (100%), whilst 8 out of 12 mice showed reduced skeletal tumours in the loaded tibias (67%), with 4 having no tumour in the loaded leg (33%). Tumour burden (Flux: photon/second) in the non-loaded tibias was 134% higher than that in the loaded tibias. Micro-CT analysis suggested that loaded tibias had significantly increased trabecular (BV/TV) and cortical bone volume and trabecular thickness (Tb.Th) (p<0.001). Surprisingly, treadmill exercised mice had higher tumour burden (~91%) in the hind limbs compared to the sedentary controls (P<0.05), with no statistically significant improvement in bone mass examined by micro-CT. In the loading withdrawal group, 6 out of 8 mice (75%) showed larger tumour size in the loading withdrawal tibias than in the non-loaded tibias, while only two mice (25%) had smaller or no tumour in the loading withdrawal tibias. Tumor burden were ~90% higher in the loading withdrawal tibias (p<0.05, t-test). This is associated with fast diminishing osteogenic response within a week after ceasing the loading stimulus, confirmed using micro-CT analysis by comparing percentage changes of BV/TV and Tb.Th among baseline, 1-week loading, and loading withdrawn groups. Conclusion: The continuity of high-intensity load bearing exercise is critical to prevent PCa growth in bone, possibly via maintaining the balance of bone remodelling towards osteoblastic bone formation. Mild aerobic exercise evaluated here was unable to significantly improve bone mass or achieve the benefits in inhibiting PCa bone metastases observed with high intensity loading. Citation Format: Ning Wang, Hector M. Arredondo, Alexandria R. Sprules, Colby L. Eaton. Continuous load bearing exercise inhibits the development of prostate cancer bone metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3481.

Myocarditis has been a rare, but well-documented side effect of the mRNA-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as a complication of viral infections including SARS-CoV-2. However, myopericarditis as a complication of monoclonal antibody infusion or as a complication of allergic reaction to antibody infusions might be underreported.We report the case of a 30-year-old man with a previous diagnosis of coronavirus disease 2019 (COVID-19) infection one week prior to presentation, unvaccinated for SARS-CoV-2, who was referred from a monoclonal infusion center where he received casirivimab/imdevimab and 15 minutes after the infusion began to complain of chills, chest pain, shortness of breath, and was hypotensive. In the infusion center, the patient received epinephrine and diphenhydramine and was directed to the ER, where the patient was febrile, tachycardic, and hypotensive. Initial troponin was 1.91 which peaked at 11.73 and CK-MB which peaked at 21.2. EKG had no ischemic changes. A two-dimensional echocardiogram showed an ejection fraction (EF) of about 45%, with a left ventricular dysfunction and trivial posterior pericardial effusion, and it was diagnosed as myopericarditis. On admission, he was started on full-dose enoxaparin, aspirin, fluid resuscitation, steroids, remdesevir, and bilevel positive airway pressure (BiPap) due to his respiratory compromise. Three days later, with clinical improvement, a repeat echocardiogram showed EF of 65%, with normal ventricular contractility and no pericardial effusion. The patient was discharged home with close cardiology follow-up.Though this could be a simple case of viral myopericarditis with troponinemia secondary to demandischemia, the differential should be broadened to complication of monoclonal antibody, given the sudden symptom onset after infusion completion and/or a possible Kounis syndrome. Though there have not been any reported cases of casirivimab/imdevimab causing myopericarditis, adverse cardiac events after monoclonal therapy have been reported mainly in cancer patients receiving monoclonal infusions.