Objective To study the effect of intra-tumor injection of slow-release 5-FU on pancreatic carcinoma cells in nude mice,and on changes in serum tumor markers and cellular immunity of patients with pancreatic carcinoma.Methods (1) In vitro experiments, the releasing action and anti-tumor effect of slow-release 5-FU were studied. Measurement of the concentration of effused fluid,calculation of amount of drug released,and observation of the inhibitory effects of effused fluid on PC3 strains of pancreatic cancer cellswere perfomed.(2) Human pancreatic carcinoma strain PC-3 cells were cultured and inoculated into 60 nude mice,and were randomly divided into 5 groups according to various treatments received: NS injection as control group(A group), 5-FU (10 mg/kg)IV injection group(B group), stroma implant group(C group), intra-tumor injection of high dose slow-release 5-FU (4mg/kg) group(D group) and intra-tumor injection of low dose slow-release 5-FU (1mg/kg) group(E group). Tumor size were measured before and 14 days after treatment. On week 2, histological changes of the tumors were examined. The apoptotic index (AI) of the tumor cells was detected by terminal-deoxynucleotide transferase mediated d-UTP nick end labeling(TUNEL) and expression of bcl-2 and Bax by immunohistochemistry.(3) 69 cases of unresectable pancreatic carcinoma were divided into 3 groups randomly:intra-tumor injection of slow-release 5-FU treated group(treatment group), intra-venous injection of 5-FU group( chemotherapy group), and control group. The serum values of CD3+, CD4+, CD8+, CD4+/ CD8+, NK cells, CEA, CA50, CA19-9, CA125 and CA242 were measured in all patients 1 day before and 14 days after operation. Results (1) There was 0.85 mg 5-FU released in the 1st day and 0.45 mg 5-FU released in the 3rd day. The release remained constant at 0.25 mg and continued for about 14 days. (2) The tumor growth suppression rate on the 1st day by effusion fluid of slow-release 5-FU was 60.27% and on the 3rd day was 34.25%. Later, it remained at about 25.00%. The tumor growth rate was slower in D and E group than in other groups (P

OBJECTIVETo investigate the synergistic antitumor effects of combined use of p14ARF gene and 5-fluorouracil (5-Fu) in pancreatic cancer.

METHODSA human pancreatic cancer cell line PC-3 was transfected with lipofectin-mediated recombinant p14ARF gene, and was then administered with 5-Fu. Cell growth, morphological changes, cell cycle, apoptosis, and molecular changes were measured using the MTT assay, flow cytometry, RT-PCR, Western blotting, and immunocytochemical assays.

RESULTSAfter transfection of p14ARF, cell growth was obviously inhibited, resulting in an accumulation of cells in the G(1) phase. The proportion of cells in the G(1) phase was significantly increased from 58.51% to 75.92%, and in the S and G(2)/M phases decreased significantly from 20.05% to 12.60%, and from 21.44% to 11.48%, respectively, as compared with those of the control groups. PC-3/p14ARF cells that underwent 5-Fu treatment had significantly greater G(2)/M phase accumulation, from 11.48% to 53.47%. The apoptopic index was increased in PC-3/p14ARF cells from 3.64% to 19.62%. The MTT assay showed p14ARF-expressing cells were significantly more sensitive to 5-Fu (0.01 - 10 mg/L) than those devoid of p14ARF expression (P < 0.01). Western blotting showed p14ARF upregulates p53 expression.

CONCLUSIONCombined use of p14ARF gene and 5-Fu acts synergistically to inhibit pancreatic cancer cell proliferation, suggesting a new anticancer strategy.

Fluorouracil ; pharmacology ; Humans ; Pancreatic Neoplasms ; genetics ; therapy ; Transfection ; Tumor Cells, Cultured ; Tumor Suppressor Protein p14ARF ; genetics ; Tumor Suppressor Protein p53 ; genetics ; Up-Regulation ; physiology

Abstract OBJECTIVE To explore the efficacy and safety of triptorelin in the treatment of central precocious puberty in girls. METHODS A total of 49 girls with central precocious puberty who were treated at Haining People's Hospital's pediatric endocrinology clinic from January 2020 to August 2022 were included in this study. These patients were treated with triptorelin according to standardized protocols and followed up for at least one year. The therapeutic efficacy and safety were analyzed and compared before treatment, after 6 months of treatment, and after 12 months of treatment. RESULTS After 6 and 12 months of treatment, there were no significant changes in uterine and ovarian volume, but both showed a reduction compared to before treatment. The Tanner stage of breast development decreased after treatment, and the luteinzing hormone levels measured by a simple stimulation test decreased compared to before treatment. Body mass index gradually increased, while bone age/chronology age ratio gradually decreased. These differences between the time points were statistically significant(P<0.05). The growth rate was highest in the first 3 months of treatment, and then gradually decreased in some patients. Three cases experienced minor vaginal bleeding after treatment. Additionally, parents expressed concerns about the use of growth hormone due to drug adverse reactions. CONCLUSION Triptorelin effectively suppresses the hypothalamic- pituitary-gonadal axis and delays skeletal maturation in girls with central precocious puberty. Apart from some cases of decreased growth rate and minor vaginal bleeding, adverse reactions are minimal during treatment.