Ozone combined with doxorubicin exerts cytotoxic and anticancer effects on Luminal-A subtype human breast cancer cell line

SUMMARY OBJECTIVE: We aimed to examine the potential anticancer effects of ozone applied after chemotherapeutic treatment with different concentrations of doxorubicin in Luminal-A subtype of human breast cancer cell line (MCF-7) and compare the results with effects on L929 fibroblast cell line. METHODS: Both cell lines were incubated with increasing doses of doxorubicin (1-50 μM) for 24 h at 37°C. Then, half of groups were incubated with 30 μg/mL ozone for 25 min as combination groups. Cell viability was analyzed by MTT assay, apoptosis by flow cytometry, and levels of tumor necrosis factor alpha, transforming growth factor beta, and matrix metalloproteinase-2 and MMP-9 by immunocytochemistry. RESULTS: Doxorubicin + ozone treatment enhanced viability of L929 (p<0.01) but reduced viability of MCF-7 compared to only doxorubicin-applied cells without ozone treatment (p<0.001). This combined treatment also enhanced apoptotic effect of doxorubicin on MCF-cells (p<0.001), but not on L929. It significantly increased all protein levels of L929 compared with those of other groups (p<0.05 for tumor necrosis factor alpha and MMP-2; p<0.01 for transforming growth factor beta and MMP-9). This treatment reversed the effect of doxorubicin on tumor necrosis factor alpha levels and considerably reduced MMP-2 and MMP-9 levels of MCF-7 compared with those of control group (p<0.01 and p<0.001, respectively). CONCLUSION: Ozone treatment potentiated the apoptotic and anticancer activities of doxorubicin in MCF-7 cells and showed repairing and healing effect on healthy fibroblast cells, which were damaged from cytotoxic effects of chemotherapeutic agent. MCF-7 cells may acquire sensitivity against the doxorubicin combined with ozone treatment through activating tumor necrosis factor alpha, MMP-2, and MMP-9 expressions.

Cordycepin prevents the esophageal stricture formation in the alkali-burn rat model by exerting anti-inflammatory and antifibrotic effects

ABSTRACT Purpose To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. Methods Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. Results Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). Conclusions The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.

A comparison of the quantitative evaluation of in situ parathyroid gland perfusion by indocyanine green fluorescence angiography and by visual examination in thyroid surgery

ABSTRACT Objective The most vital complications of thyroidectomy are recurrent nerve damage and hypocalcaemia. We aimed to compare the tissue perfusion scores (PS) of IG fluorescence angiography (IGFA) and visual examination by the surgeon after total thyroidectomy. Subjects and methods Forty-three patients were accepted into the study. Localisation of the parathyroid gland (PG) was determined by the naked eye and scored in terms of tissue perfusion. The averages of fluorescent light intensities for each IGFA were calculated, the perfusions were scored and compared with the PS given by the surgeon. Biochemical parameters were noted. Results 37.2% of patients had autotransplanted PGs, according to their visual scores. The means of IGFA-PS for PGs scored as 0, 1 or 2 on visual inspection were 48.58 ± 4.49 [30-70], 89.65 ± 8.93 [36-144] and 158.76 ± 8.93 [70-253], respectively, which correlated with the visual PSs in a statistically significant manner (P < 0.0001). The predictive cut-off value for IGFA-PS was determined to be 70, given a visual PS of 0 (95% CI [0.72-0.85]), and this was interpreted to be a candidate cut-off point for the autotransplantation of PGs. Conclusion IGFA scoring may be considered as an operative predictor, providing objective criteria to evaluate the tissue and blood perfusion of PGs after thyroidectomy. IGFA scoring may be considered to have value in minimising postoperative permanent hypoparathyroidism in patients.

Evaluation of prophylactic and therapeutic effects of sildenafil on acute radiation proctitis in rats

Abstract Purpose: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). Methods: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. Results: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group. While the prophylaxis group and the treatment group had significantly lower scores. High-dose group showed similar results as prophylaxis group. Histopathological findings of the prophylaxis group was more significant than the treatment group. Immunoreactivities of IL-1β, FGF-2, TNF- α and HIF-1α increased in the control group especially in the epithelial and cryptic regions. On the contrary, sildenafil application caused significant decreases of inflammatory markers in all treatment groups, specifically better results in the prophylaxis group. Conclusion: The sildenafil has anti-inflammatory effects on ARP, as well as protective effects against ARP and the protective effect of sildenafil surpasses its therapeutic effect histopathologically.