COVID-19 pandemic: changes in cancer admissions.

BACKGROUND: COVID-19 pandemic could create a collateral damage to cancer care denoting disruptions in care due to a significant burden on healthcare and resource allocations. Herein, we evaluate the early changes in the inpatient and outpatient oncology clinics to take a snapshot of this collateral damage at Hacettepe University Cancer Institute. METHODS: Patients applying the outpatient clinic and outpatient palliative care (OPC) clinic for the first time and patients admitted to inpatient wards in the first 30 days after the first case of COVID-19 in Turkey were evaluated. These data were compared with data from the same time frame in the previous 3 years. RESULTS: The mean number of daily new patient applications to the outpatient clinic (9.87±3.87 vs 6.43±4.03, p<0.001) and OPC clinic (3.87±1.49 vs 1.13±1.46, p<0.001) was significantly reduced compared with the previous years. While the number of inpatient admissions was similar for a month frame, the median duration of hospitalisation was significantly reduced. The frequency of hospitalisations for chemotherapy was higher than in previous years (p<0.001). By comparison, the rate of hospitalisations for palliative care (p=0.028) or elective interventional procedures (p=0.001) was significantly reduced. CONCLUSION: In our experience, almost all domains of care were affected during the pandemic other than patients' systemic treatments. There were significant drops in the numbers of newly diagnosed patients, patients having interventional procedures and palliative care services, and these problems should be the focus points for the risk mitigation efforts for prevention of care disruptions.

Anti-prostate cancer activity of a nanoformulation of the spleen tyrosine kinase (SYK) inhibitor C61.

Patients with advanced or metastatic castration-resistant prostate cancer have a dismal prognosis and are therefore in urgent need for therapeutic innovations. Spleen tyrosine kinase has emerged as a new molecular target for castration-resistant prostate cancer. This study was done to test the cytotoxicity of the lead nanoformulation of a potent spleen tyrosine kinase inhibitor, C61-LNP, against the human prostatic carcinoma cell line, PC-3. PC-3 cells were treated with various concentrations of C61-LNP either alone or in combination with cisplatin (CDDP) for 24, 48 and 72 hours. The cell viability was evaluated by MTS assay. Cellular expression levels of various regulatory proteins in treated PC-3 cells were evaluated by Western blot analyses. C61-LNP exhibited dose-dependent cytotoxicity against PC-3 cells. C61-LNP, as well as C61-LNP + CDDP treatments, caused pro-apoptotic proteomic changes including an increase in cleaved fragments of caspases-3 and -9 consistent with caspase activation as well as an improvement in the anti-apoptotic Bcl2 and Bax levels. The combination of C61-LNP and CDDP changed in alterations of the cell cycle regulatory proteins p53, p21, p27, cyclin D1 and cyclin E levels. C61-LNP exhibited cytotoxicity against the castration-resistant prostate cancer cell line PC3. It also caused alterations in expression levels of regulatory proteins involved in apoptosis and cell cycle regulation and these effects were not abrogated by the standard chemotherapy drug CDDP. We are planning to further develop C61-LNP as a selective spleen tyrosine kinase inhibitor as part of a multi-modality treatment strategy for advanced/metastatic castration-resistant prostate cancer.

Chemopreventive efficacy of stampidine in a murine breast cancer model.

Background: The purpose of the present study was to examine the chemopreventive effect of stampidine, an aryl phosphate derivative of stavudine, in side by side comparison with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced murine breast cancer model.Methods: Groups of 20 female mice were challenged with the DMBA. DMBA-challenged mice were assigned to various chemoprevention treatments, including stampidine, paclitaxel, and stampidine plus paclitaxel according to the same treatment schedules for 25 weeks.Results: Stampidine resulted in substantially reduced numbers of tumors, tumor weight as well as tumor size in DMBA-treated mice. Stampidine was as effective as paclitaxel in the model and their combination exhibited greater chemopreventive activity, as measured by reduced tumor incidence and improved tumor-free survival as well as overall survival of DMBA-treated mice. The length of time for the initial tumor to appear in DMBA-challenged mice treated with stampidine was longer than that of mice treated DMBA-challenged control mice. Tumors from mice treated with stampidine or stampidine plus paclitaxel displayed unique changes of a signature protein cassette comprised BRCA1, p21, Bax, and Bcl-2.Conclusion: Stampidine has potent chemopreventive activity and is as effective as the standard chemotherapy drug paclitaxel in the chemical carcinogenesis.