Effects of Repeated Doses of the Vero Cell Vaccine (SARS-Cov-2 Inactivated Vaccine) on Renal Functions in Balb/C Albino Mice.

Objective: Many of the vaccines developed for COVID-19 have been approved for clinical emergency use before their safety and preclinical studies have been completed. The main aim of this study was to investigate the effects of an inactivated SARS-CoV-2 virus vaccine (Vero cells) on renal function in Balb/C Albino mice. Methods: 21 healthy, 6-8 week old BALB/c male mice were divided into three equal groups, and 0.10 mL of intramuscular saline equal to the vaccine dose volume was administered to the first group. To the second group, a single dose of 0.10 mL 120 U of Vero cell inactive SARS COV-2 vaccine was administered intramuscularly. Group 3 received two consecutive doses of 0.10 mL 120 U intramuscular Vero cell inactive SARS COV-2 vaccine, 14 days apart. After administration, the clinical status, fecal and urine status, nutritional status and kidney histopathology of the mice were evaluated. Results: It was determined that no acute toxic symptoms were observed in the mice administered the vaccine, they were in good condition, and there was no significant stimulatory reaction related to the vaccine in the tissues of the injected local area. There was no difference in feed consumption, water consumption, and body weight gains between the control group, the groups that received a single dose of vaccine, and the groups that received two doses of vaccine (p>0.05). No difference was found between the groups when urine and feces amounts were compared (p>0.05). No difference was found between the groups when urinary urea, creatinine, and serum BUN, creatinine levels were compared (p>0.05). No difference was found in the histopathological evaluation of the kidneys between the groups (p>0.05). Conclusion: In conclusion, single or repeated injections of the SARS-CoV-2 vaccine (Vero cells) into mice were found to have no adverse effects on the animals' overall clinical health, performance abilities and kidneys.

The effects of PKI-402 on breast tumor models' radiosensitivity via dual inhibition of PI3K/mTOR.

PURPOSE: PI3K/Akt/mTOR pathway activation causes relapse and resistance after radiotherapy in breast cancer (BC). We aimed to radiosensitize BC cell lines to irradiation (IR) by PKI-402, a dual PI3K/mTOR inhibitor. METHODS: We performed cytotoxicity, clonogenicity, hanging drop, apoptosis and double-strand break detection, and phosphorylation of 16 essential proteins involved in the PI3K/mTOR pathway. RESULTS: Our findings showed that PKI-402 has cytotoxic efficiency in all cell lines. Clonogenic assay results showed that PKI-402 plus IR inhibited the colony formation ability of MCF-7 and breast cancer stem cell lines. Results showed that PKI-402 plus IR causes more apoptotic cell death than IR alone in the MCF-7 cells but did not cause significant changes in the MDA-MB-231. γ-H2AX levels were increased in MDA-MB-231 in PKI-402 plus IR groups, whereas we did not observe any apoptotic and γ-H2AX induction in BCSCs and MCF-10A cells in all treatment groups. Some pivotal phosphorylated proteins of the PI3K/AKT pathway decreased, several proteins increased and others did not change. CONCLUSION: In conclusion, if the combined use of PKI-402 with radiation is supported by in vivo studies, it can contribute to the treatment options and the course of the disease.

Concordance in molecular genetic analysis of tumour tissue, plasma, and exhaled breath condensate samples from lung cancer patients.

AIM: Lung adenocarcinoma is characterized by poor prognosis and short survival rates. Therefore, tools to identify the tumoural molecular structure and guide effective diagnosis and therapy decisions are essential. Surgical biopsies are highly invasive and not conducive for patient follow-up. To better understand disease prognosis, novel non-invasive analytic methods are needed. The aim of the present study is to identify the genetic mutations in formalin-fixed paraffin-embedded (FFPE) tissue, plasma, and exhaled breath condensate (EBC) samples by next-generation sequencing and evaluate their utility in the diagnosis and follow-up of patients with lung adenocarcinoma. METHOD: FFPE, plasma, and EBC samples were collected from 12 lung adenocarcinoma patients before treatment. DNA was extracted from the specimens using an Invitrogen PureLink Genomic DNA Kit according to the manufacturer's instructions. Amplicon-based sequencing was performed using Ion AmpliSeq Colon and Lung Cancer Research Panel v2. RESULTS: Genetic alterations were detected in all FFPE, plasma, and EBC specimens. The mutations in PIK3CA, MET, PTEN, SMAD4, and FGFR2 genes were highly correlated in six patients. Somatic and novel mutations detected in tissue and EBC samples were highly correlated in one additional patient. The EGFR p.L858R and KRAS p.G12C driver mutations were found in both the FFPE tissue specimens and the corresponding EBC samples of the lung adenocarcinoma patients. CONCLUSION: The driver mutations were detected in EBC samples from lung adenocarcinoma patients. The analysis of EBC samples represents a promising non-invasive method to detect mutations in lung cancer and guide diagnosis and follow-up.