ABSTRACT
BACKGROUND: RAD18 plays an important role in DNA damage repair by inducing monoubiquitinated PCNA (mUB-PCNA) in both cancer and normal tissues. Previous studies have not determined the significance of RAD18 expression in clinical gastric cancer (GC) samples. Thus, this study aimed to clarify the expression and functional significance of RAD18 in GC. METHODS: Overall, 96 resected GC samples were subjected to an immunohistochemical analysis of RAD18. GC cell lines were also subjected to functional RNA interference analyses of RAD18. RESULTS: RAD18 expression was predominantly nuclear and was observed at higher levels in GC tissues than in normal tissues. In GC tissues, strong RAD18 expression was associated with progression of lymph node metastasis (p = 0.0001), lymphatic invasion (p = 0.0255), venous invasion (p < 0.0001), recurrence (p = 0.028), and disease stage (p = 0.0253). Moreover, GC patients with high tumor RAD18 expression had shorter overall survival (p = 0.0061) and recurrence-free survival durations (p = 0.035) than those with low tumor RAD18 expression. RAD18 knockdown inhibited GC proliferation and invasiveness and increased chemosensitivity by suppressing mUB-PCNA. CONCLUSIONS: RAD18 expression may be a useful marker of progression and poor prognosis of GC. Moreover, therapeutic strategies that target RAD18 might be a novel chemosensitizer to eradicate the refractory GC.
Subject(s)
DNA-Binding Proteins , Stomach Neoplasms , Ubiquitin-Protein Ligases , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Cell Line, Tumor , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Disease Progression , Humans , Neoplasm Invasiveness , Prognosis , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Ubiquitin-Protein Ligases/biosynthesis , Ubiquitin-Protein Ligases/geneticsABSTRACT
PURPOSE: To investigate the efficacy and safety of uterine artery embolization (UAE) followed by dilation and curettage (D&C) as a treatment for cesarean scar pregnancy (CSP) and to assess pregnancy outcomes after the treatment. MATERIALS AND METHODS: We retrospectively analyzed 33 CSP patients treated with UAE followed by D&C. The serum level of beta human chorionic gonadotropin (ß-hCG) normalization, hospitalization, menstruation, and successful pregnancy after treatment was assessed as clinical and pregnancy outcomes. RESULTS: A total of 33 patients were initially treated without severe complications. However, four patients required additional systemic chemotherapy. ß-hCG normalization took 35.5 ± 14.9 days (range 13-79), and the hospitalization was 6.5 ± 2.5 days (2-15). All patients resumed normal menstruation after 36 ± 19.2 days (12-86). Of 16 of 33 patients who desired pregnancy after the treatment, seven patients (43.8%) had uneventful parturition. CONCLUSIONS: UAE combined with D&C was efficient and safe for CSP management. This minimally invasive procedure may be considered as one of the treatment options which enable preservation of fertility after treatment.
Subject(s)
Cesarean Section , Dilatation and Curettage/methods , Fertility , Pregnancy, Ectopic/surgery , Uterine Artery Embolization/methods , Adult , Cicatrix , Combined Modality Therapy/methods , Female , Humans , Methotrexate/administration & dosage , Pregnancy , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: To investigate the effect of pregnancy and type of gadolinium (Gd)-based contrast agents (GBCAs) on organ retention of Gd in mother and pup mice after maternal administration. MATERIALS AND METHODS: Gd-DTPA-BMA (gadodiamide) or Gd-DOTA (gadoterate dimeglumine) was administered (2.0 mmol/kg of maternal weight) four times to pregnant Balb/c mice from gestational day 16-19, respectively. At 28 days after birth, they were euthanized and their organs (blood, brain, liver, kidney, spleen, and bone) were removed for the measurement of Gd by inductively coupled plasma mass spectrometry. RESULTS: Gd retention in maternal organs was generally lower than that in the organs of non-pregnant mice in both Gd-DTPA-BMA and Gd-DOTA groups. Significantly higher Gd retention was observed in the organs of pups whose mothers were administered Gd-DTPA-BMA as compared to those whose mothers were administered Gd-DOTA. Tissue-to-muscle ratio in the brains of pups was higher than that of mothers. CONCLUSION: We demonstrated in utero transplacental Gd retention in pups. In various organs in both mothers and pups, Gd retention was consistently higher for Gd-DTPA-BMA than Gd-DOTA administration. Pregnancy affected Gd retention in many maternal organs.
