Antitumor Effects of Cannabinoids in Human Pancreatic Ductal Adenocarcinoma Cell Line (Capan-2)-Derived Xenograft Mouse Model

BackgroundPancreatic cancer is considered a rare type of cancer, but the mortality rate is high. Cannabinoids extracted from the cannabis plant have been interested as an alternative treatment in cancer patients. Only a few studies are available on the antitumor effects of cannabinoids in pancreatic cancer. Therefore, this study aims to evaluate the antitumor effects of cannabinoids in pancreatic cancer xenografted mouse model.Materials and MethodsTwenty-five nude mice were subcutaneously transplanted with a human pancreatic ductal adenocarcinoma cell line (Capan-2). All mice were randomly assigned into 5 groups including negative control (gavage with sesame oil), positive control (5 mg/kg 5-fluorouracil intraperitoneal administration), and cannabinoids groups that daily received THC:CBD, 1:6 at 1, 5, or 10 mg/kg body weight for 30 days, respectively. Xenograft tumors and internal organs were collected for histopathological examination and immunohistochemistry.ResultsThe average tumor volume was increased in all groups with no significant difference. The average apoptotic cells and caspase-3 positive cells were significantly increased in cannabinoid groups compared with the negative control group. The expression score of proliferating cell nuclear antigen in positive control and cannabinoids groups was decreased compared with the negative control group.ConclusionsCannabinoids have an antitumor effect on the Capan-2-derived xenograft mouse model though induce apoptosis and inhibit proliferation of tumor cells in a dose-dependent manner

Investigation of Genes and Proteins Expression Associating Serotonin Signaling Pathway in Lung and Pulmonary Artery Tissues of Dogs with Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease: The Preliminary Study

Pulmonary hypertension (PH) is defined as an increase in pulmonary vascular pressure. It is one of the most common complications that occur as a result of degenerative mitral valve disease (DMVD) in dogs. Serotonin (5-HT) can trigger the development of PH. Accordingly, this study investigated the changes in the expression of genes and proteins associated with local 5-HT signaling in the lungs and pulmonary arteries (PA) of dogs with PH secondary to DMVD. Lung and PA tissue samples were collected from the cadavers of fourteen small-breed dogs and divided into normal (n = 4), DMVD (n = 5) and DMVD with PH (n = 5) groups. Gene expression (tph1, slc6a4 and htr2a) was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of proteins (TPH-1, SERT, 5-HTR2A, ERK1/2 and pERK1/2) was examined by Western blot analysis and immunohistochemical staining. The results showed that the expression of genes and proteins evaluated by qRT-PCR and Western blot analysis in lung and PA tissues did not differ among groups. However, the expression of proteins related to 5-HT signaling tended to be upregulated in PA tissues from DMVD dogs with and without PH. Immunohistochemical examination revealed the overexpression of these proteins in the DMVD and DMVD with PH groups in lung tissue. These findings suggest a local effect of 5-HT signaling in DMVD dogs with and without PH

Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers

Abstract An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential biological risks. Intranasal NAS administration in rats showed no circulatory presence of human IgG1 anti-SARS-CoV-2 antibodies within 120 h. A double-blind, randomized, placebo-controlled trial (NCT05358873) was conducted on 36 healthy volunteers who received either NAS or a normal saline nasal spray. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. NAS was well tolerated, with no significant adverse effects during the 14 days of the study. The SARS-CoV-2 neutralizing antibodies were detected based on the signal inhibition percent (SIP) in nasal fluids pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SIP values in nasal fluids collected immediately or 6 h after NAS application were significantly increased from baseline for all three variants tested, including ancestral, Delta, and Omicron BA.2. In conclusion, NAS was safe for intranasal use in humans to increase neutralizing antibodies in nasal fluids that lasted at least 6 h