ABSTRACT
Purpose@#Esophagojejunostomy leakage after total gastrectomy for gastric cancer is one of the most serious and sometimes life-threatening adverse events. The purpose of this study was to evaluate complications after total gastrectomy in patients with gastric cancer during the period when Histoacryl (B. Braun) injection was performed. Therapeutic outcome of endoscopic Histoacryl injection for esophagojejunostomy leakage was also determined. @*Methods@#This was a single-center retrospective study. Between January 2016 and December 2021, clinicopathologic characteristics and surgical outcomes of 205 patients who underwent total gastrectomy were investigated. Baseline characteristics and clinical outcomes of 10 patients with esophagojejunostomy leakage were also investigated. @*Results@#Postoperative complication and mortality rates of total gastrectomy in 205 patients were 25.4% and 0.9%, respectively. Serious complications more than Clavien-Dindo IIIb accounted for 6.3%. Ten (4.9%) esophagojejunostomy leakages occurred in 205 patients. Among 10 esophagojejunostomy leakage patients, endoscopic Histoacryl injection was performed on eight patients and leakage was successfully managed with endoscopic Histoacryl injection in seven patients (87.5%). Mean postinjection hospital stay of seven successfully managed patients was 13.8 days. They were able to drink water at 1–6 days after injection.Among eight patients with endoscopic Histoacryl injection, six patients were injected once and two patients were injected three times. @*Conclusion@#Endoscopic Histoacryl injection for esophagojejunostomy leakage after total gastrectomy can be considered as a useful treatment for some selected cases.
ABSTRACT
Axl receptor tyrosine kinase has been implicated in cancer progression, invasion, and metastasis in various cancer types. Axl overexpression has been observed in many cancers, and selective inhibitors of Axl, including R428, may be promising therapeutic agents for several human cancers, such as breast, lung, and pancreatic cancers. Here, we examined the cell growth inhibition mediated by R428 and auranofin individually as well as in combination in the human breast cancer cell lines MCF-7 and MDAMB-231 to identify new advanced combination treatments for human breast cancer. Our data showed that combination therapy with R428 and auranofin markedly inhibited cancer cell proliferation. Isobologram analyses of these cells indicated a clear synergism between R428 and auranofin with a combination index value of 0.73. The combination treatment promoted apoptosis as indicated by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. Cancer cell migration was also significantly inhibited by this combination treatment. Moreover, we found that combination therapy significantly increased the expression level of Bax, a mitochondrial proapoptotic factor, but decreased that of the X-linked inhibitor of apoptosis protein. Furthermore, the suppression of cell viability and induction of Bax expression by the combination treatment were recovered by treatment with N-acetylcysteine. In conclusion, our data demonstrated that combined treatment with R428 and auranofin synergistically induced apoptosis in human breast cancer cells and may thus serve as a novel and valuable approach for cancer therapy.
ABSTRACT
Steroid sulfatase (STS) is an enzyme responsible for the hydrolysis of aryl and alkyl sulfates. STS plays a pivotal role in the regulation of estrogens and androgens that promote the growth of hormone-dependent tumors, such as those of breast or prostate cancer. However, the molecular function of STS in tumor growth is still not clear. To elucidate the role of STS in cancer cell proliferation, we investigated whether STS is able to regulate the integrin signaling pathway. We found that overexpression of STS in HeLa cells increases the protein and mRNA levels of integrin β1 and fibronectin, a ligand of integrin α5β1. Dehydroepiandrosterone (DHEA), one of the main metabolites of STS, also increases mRNA and protein expression of integrin β1 and fibronectin. Further, STS expression and DHEA treatment enhanced phosphorylation of focal adhesion kinase (FAK) at the Tyr 925 residue. Moreover, increased phosphorylation of ERK at Thr 202 and Tyr 204 residues by STS indicates that STS activates the MAPK/ERK pathway. In conclusion, these results suggest that STS expression and DHEA treatment may enhance MAPK/ERK signaling through up-regulation of integrin β1 and activation of FAK.