X-ray inhibits FUT4-mediated proliferation in A549 cells by downregulating SP1 expression.

Objective: To identify the mechanism of down-regulation of Lewis Y antigen caused by X-ray irradiation. METHODS: The present original research study was conducted at Zhejiang University City College, Hangzhou, Republic of China, from 2020 to 2022. Western blotting, Co-immunoprecipitation (CO-IP), electrophoretic mobility shift assay and Cell Counting Kit-8 (CCK8) were performed to confirm the effect of X-ray irradiation on A549 cell proliferation and its mechanism. Data was analysed using Statistical Package for Social Sciences (SPSS) 11.5. RESULTS: The expressions of fucosyltransferase IV and Lewis Y were decreased after X-ray irradiation, thus inhibiting the proliferation of A549 lung cancer cells. Deoxyribonucleic acid damage caused by the irradiation caused higher level of poly- adenosinediphosphate-ribosylated Specific Protein 1(SP1), and translocation of SP1 from the nucleus, decreasing the expression of fucosyltransferase IV and Lewis Y. Conclusion: There was a significant role of glycosylation in radiation therapy for lung cancer.

A novel glycosylation-related gene signature predicts survival in patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common malignant tumor that seriously affects human health. Previous studies have indicated that abnormal levels of glycosylation promote progression and poor prognosis of lung cancer. Thus, the present study aimed to explore the prognostic signature related to glycosyltransferases (GTs) for LUAD. METHODS: The gene expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and GTs were obtained from the GlycomeDB database. Differentially expressed GTs-related genes (DGTs) were identified using edge package and Venn diagram. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ingenuity pathway analysis (IPA) methods were used to investigate the biological processes of DGTs. Subsequently, Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct a prognostic model for LUAD. Kaplan-Meier (K-M) analysis was adopted to explore the overall survival (OS) of LUAD patients. The accuracy and specificity of the prognostic model were evaluated by receiver operating characteristic analysis (ROC). In addition, single-sample gene set enrichment analysis (ssGSEA) algorithm was used to analyze the infiltrating immune cells in the tumor environment. RESULTS: A total of 48 DGTs were mainly enriched in the processes of glycosylation, glycoprotein biosynthetic process, glycosphingolipid biosynthesis-lacto and neolacto series, and cell-mediated immune response. Furthermore, B3GNT3, MFNG, GYLTL1B, ALG3, and GALNT13 were screened as prognostic genes to construct a risk model for LUAD, and the LUAD patients were divided into high- and low-risk groups. K-M curve suggested that patients with a high-risk score had shorter OS than those with a low-risk score. The ROC analysis demonstrated that the risk model efficiently diagnoses LUAD. Additionally, the proportion of infiltrating aDCs (p < 0.05) and Tgds (p < 0.01) was higher in the high-risk group than in the low-risk group. Spearman's correlation analysis manifested that the prognostic genes (MFNG and ALG3) were significantly correlated with infiltrating immune cells. CONCLUSION: In summary, this study established a novel GTs-related risk model for the prognosis of LUAD patients, providing new therapeutic targets for LUAD. However, the biological role of glycosylation-related genes in LUAD needs to be explored further.

Effects of neoadjuvant hyperthermic intraperitoneal chemotherapy on chemotherapy response score and recurrence in high-grade serous ovarian cancer patients with advanced disease: A multicentre retrospective cohort study.

OBJECTIVE: To investigate whether the combination of neoadjuvant hyperthermic intraperitoneal chemotherapy (NHIPEC) plus intravenous neoadjuvant chemotherapy (IV NACT) has superior efficacy to IV NACT alone. DESIGN: Retrospective cohort study. SETTING: Two tertiary referral university hospitals. POPULATION: Patients with ovarian cancer who received NACT-interval debulking surgery (IDS) between 2012 and 2020. METHODS: The tumour response to NACT was evaluated with the chemotherapy response score (CRS) system. Survival outcomes were compared. MAIN OUTCOME MEASURES: CRS 3, progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 127 patients were included, and 46 received NHIPEC plus IV NACT. The addition of NHIPEC was independently associated with an increased likelihood of CRS 3 (p = 0.033). Patients who received NHIPEC + IV NACT had significantly improved PFS compared with those who received IV NACT alone (median PFS: 22 versus 16 months, p < 0.001). The use of NHIPEC was identified as an independent predictor of PFS (p < 0.0001). OS did not differ significantly between treatment groups (p = 0.062), although a trend favouring NHIPEC was noted. Incidence of grade 3-4 adverse events and the surgical complexity score of IDS were similar between the two groups. CONCLUSIONS: Compared with IV NACT alone, the combination of NHIPEC and IV NACT resulted in improved tumour response and longer PFS. The addition of NHIPEC did not increase the risk of adverse effects or affect the complexity of IDS.

Association between subtypes of metabolic syndrome and prognosis in patients with stage I endometrioid adenocarcinoma: A retrospective cohort study.

Purpose: To investigate the association between subtypes of metabolic syndrome (MetS) and prognosis of patients with stage I endometrioid adenocarcinoma. Patients and methods: Patients with stage I endometrioid adenocarcinoma who received surgical treatment as primary therapy at the Department of Gynecology of the Sun Yat-sen Memorial Hospital between June 2015 and December 2019 were retrospectively enrolled. According to the diagnosis criteria of MetS, the patients were categorized as patients without MetS, patients with MetS but without raised fasting plasma glucose (FPG, including previously diagnosed diabetes), and patients with MetS and raised FPG. All the included patients were followed from the dates of surgery until death, June 2021, or loss to follow-up, whichever came first, and cancer recurrence (including metastasis) was studied as the main outcome. Cox regression was used to evaluate the associations between subtypes of MetS and the study outcome adjusting for potential confounding factors. Results: Among the included 387 patients with stage I endometrioid adenocarcinoma, 193 (49.9%) were without MetS, 65 (16.8%) were with FPG not involving MetS, and 129 (33.3%) were with raised FPG involved MetS. With a median follow-up of 1,253 days, the cumulative incidence of cancer recurrence was 8.76% (95% confidence interval (CI) 2.5%-14.62%), 28.31% (95% CI 2.33%-47.38%), and 7.54% (95% CI 1.54%-13.17%), respectively. After adjusting for age, menopause, histological grade, tumor size, lymph-vascular space invasion, deep myometrial invasion, and treatments, comorbid FPG not involving MetS is a stronger risk factor of cancer recurrence than comorbid raised FPG involving MetS (hazard ratio 2.82 (95% CI 1.10-7.24) versus 1.18 (95% CI 0.45-3.13)) when compared to patients without MetS. Conclusion: Comorbid MetS generally presents as a risk factor of poor prognosis in patients with stage I endometrioid adenocarcinoma after surgical treatment, but the magnitude of the association may vary between subtypes, in which FPG not involving MetS appears to be predominant.

Corrigendum to "The Protective Effect of N-Acetylcysteine on Ionizing Radiation Induced Ovarian Failure and Loss of Ovarian Reserve in Female Mouse".

[This corrects the article DOI: 10.1155/2017/4176170.].

SUMO4 small interfering RNA attenuates invasion and migration via the JAK2/STAT3 pathway in non-small cell lung cancer cells.

Small ubiquitin-like modifier 4 (SUMO4) is the latest member of the sumoylation family, which enhances the stability of protein, regulates the distribution and localization of the protein, and affects the transcription activity of the protein. However, the role of SUMO4 in non-small cell lung cancer (NSCLC) has not yet been reported. The present study first demonstrated that SUMO4 was upregulated in a number of tissues from patients with NSCLC. Immunohistochemistry was performed to demonstrate the expression level of SUMO4 in lung cancer tumor tissues. Following the transfection, The EMT status and signaling pathway activation regulated by SUMO4-siRNA was assessed by western blotting. The Transwell and wound healing assays were performed to investigate the regulatory effect of SUMO4-siRNA on cell migration and invasion. Cell Counting Kit-8 assay was performed to investigate whether SUMO4-siRNA affected the chemosensitivity of the NSCLC cells to cisplatin. Statistical analysis of immunohistochemical results from the tissues showed that the overexpression of SUMO4 was significantly associated with sex, tumor type, history of smoking, T stage and poor prognosis. It was also identified that SUMO4 small interfering RNA attenuated invasion and migration in NSCLC cell lines, as well chemosensitivity to cisplatin via the inhibition of the JAK2/STAT3 pathway. In conclusion, SUMO4 may play an important role in the poor prognosis of patients with NSCLC. The present study indicates that SUMO4 may be a potential therapeutic target for NSCLC.

LncRNA EIF3J-AS1 enhanced esophageal cancer invasion via regulating AKT1 expression through sponging miR-373-3p.

Esophageal cancer (ECa) remains a major cause of mortality across the globe. The expression of EIF3J-AS1 is altered in a plethora of tumors, but its role in ECa development and progression are undefined. Here, we show that EIF3J-AS1 is up-regulated in ECa and that its expression correlates with advanced TNM stage (P = 0.014), invasion depth (P = 0.001), positive lymph node metastasis (P < 0.001) and poor survival (OS: P = 0.0059; DFS: P = 0.0037) in ECa. Functional experiments showed that knockdown EIF3J-AS1 inhibited ECa growth and metastasis through in vitro and in vivo experiments. Regarding the mechanism, EIF3J-AS1/miR-373-3p/AKT1 established the ceRNA network involved in the modulation of cell progression of ECa cells. Overall, EIF3J-AS1 may exhibit an oncogenic function in ECa via acting as a sponge for miR-373-3p to up-regulate AKT1 mRNA level, and may serve as a potential therapeutic target and a prognostic biomarker for ECa patients.

Fucosyltransferase VII promotes proliferation via the EGFR/AKT/mTOR pathway in A549 cells.

Fucosyltransferase VII (FUT7) is one of a1,3-fucosyltransferases family that catalyzes the final fucosylation step in the synthesis of Lewis antigens and generates a unique glycosylated product sialyl Lewis X (sLeX). sLeX can serve as ligands for E- or P-selectin expressed on the cell surface and results in cancer metastasis and angiogenesis. However, the molecular biological mechanisms of FUT7 elevation in neoplastic cells are still largely unknown. In this study, we examined the impact of FUT7 on cell proliferation and migration in A549 cells by colony formation assay, cell cycle assay, gelatin zymography, wound-healing assay, transwell invasion assay and Western blot. In addition, we identified that FUT7 activated EGFR/AKT/mTOR signal pathway that correlated with sLeX augmentation. In conclusion, FUT7 overexpression augments sLeX synthesis to trigger cell proliferation via the activation of EGFR/AKT/mTOR signaling pathway, which indicated that FUT7 may be a potential therapeutic target for epithelial cancers with a high expression of FUT7 and sLeX.

The Protective Effect of N-Acetylcysteine on Ionizing Radiation Induced Ovarian Failure and Loss of Ovarian Reserve in Female Mouse.

Ionizing radiation may cause irreversible ovarian failure, which, therefore, calls for an effective radioprotective reagent. The aim of the present study was to evaluate the potential radioprotective effect of N-acetylcysteine (NAC) on ionizing radiation induced ovarian failure and loss of ovarian reserve in mice. Kun-Ming mice were either exposed to X-irradiation (4 Gy), once, and/or treated with NAC (300 mg/kg), once daily for 7 days before X-irradiation. We examined the serum circulating hormone levels and the development of ovarian follicles as well as apoptosis, cell proliferation, and oxidative stress 24 hours after X-irradiation. In addition, morphological observations on the endometrial luminal epithelium and the fertility assessment were performed. We found that NAC successfully restored the ovarian and uterine function, enhanced the embryo implantation, improved the follicle development, and altered the abnormal hormone levels through reducing the oxidative stress and apoptosis level in granulosa cells while promoting the proliferation of granulosa cells. In conclusion, the radioprotective effect of NAC on mice ovary from X-irradiation was assessed, and our results suggested that NAC can be a potential radioprotector which is capable of preventing the ovarian failure occurrence and restoring the ovarian reserve.

Clinicopathological and prognostic significance of sialyl Lewis X overexpression in patients with cancer: a meta-analysis.

Many studies have shown that sialyl Lewis X (sLe(X)) is related to cancer prognosis and clinicopathology, but failed to provide conclusive results. We conducted the present meta-analysis to identify the association between sLe(X) overexpression and cancer prognosis. We searched studies in PubMed and Embase databases. Relative risk or hazard ratio with 95% confidence intervals were estimated with the Mantel-Haenszel random-effect method and 29 studies were included. Our meta-analysis showed that sLe(X) overexpression is significantly related to lymphatic invasion, venous invasion, T stage, N stage, M stage, tumor stage, recurrence, and overall survival. In subgroup analysis, we found that cancer type and ethnicity might be two major contributing factors to the possible presence of heterogeneity among the studies. In conclusion, sLe(X) overexpression is associated with tumor metastasis, recurrence, and overall survival in cancer patients, it plays an important role in cancer prognosis.

Chemokine receptor CXCR4 expression and lung cancer prognosis: a meta-analysis.

The chemokine receptor CXCR4 is a G protein-coupled receptor that plays an important role in several biological processes, such as trafficking and homeostasis of immune cells (like T lymphocytes), alteration of cell skeleton rearrangement and cell migration. To investigate whether the CXCR4 protein impacts on lung cancer prognosis, a meta-analysis was performed. Our meta-analysis study involved 2,037 lung cancer patients from 24 studies by a comprehensive search from PubMed, Embase and CNKI databases up to September 2014. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were used to evaluate the relationship. We found that the CXCR4 expression was significantly associated with lymph node metastasis (OR = 3.79, 95% CI: 2.15-6.68), distant metastasis (OR = 3.67, 95% CI: 1.84-7.32), tumor stage (OR = 2.78, 95% CI: 1.77-4.39) and overall survival (HR = 1.63, 95% CI: 1.16-2.30). In conclusion, CXCR4 might be a new prognostic biomarker, and it might become a new diagnosis and therapeutic target in lung cancer.

Oxidative damage of DNA induced by X-irradiation decreases the uterine endometrial receptivity which involves mitochondrial and lysosomal dysfunction.

X irradiation may lead to female infertility and the mechanism is still not clear. After X irradiation exposure, significantly morphological changes and functional decline in endometrial epithelial cells were observed. The mitochondrial and lysosomal dysfunction and oxidative DNA damage were noticed after X irradiation. In addition, pretreatment with NAC, NH4Cl or Pep A reduced the X irradiation induced damages. These studies demonstrate that the oxidative DNA damage which involved dysfunctional lysosomal and mitochondrial contribute to X irradiation-induced impaired receptive state of uterine endometrium and proper protective reagents can be helpful in improving endometrial function.

Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study.

BACKGROUND AND AIMS: Many epidemiological studies have revealed a positive correlation between medical radiation exposure and the reproductive health in female childhood cancer survivors. However, because of variations in the samples size, such studies showed partly inconsistent conclusions. The aim of this meta-analysis was to clarify the association between radiotherapy and the risk of reproductive health impairment for female who survived from childhood cancer. METHODS: Fourteen cohort studies involving childhood radiotherapy were selected as the exposure of interest and the impaired reproductive health condition during the childbearing age as the outcome. Among meta-analysis of observational studies found in Pubmed and Embase from 1900 to 2014, we evaluated those relevant observational studies which surveyed the association of medical radiation and reproductive health in female childhood cancer survivors. Review Manager 5.2 and STATA 12.0 software were used to perform the meta-analysis. Study-specific estimations for each outcome were combined into a pooled relative risk (RR) with 95% confidence interval (CI) by a meta-analytic approach. RESULTS: Based on a random-effects meta-analysis, significant association between infertility (RR = 1.28, 95% CI = 1.16-1.42), acute ovarian failure (AOF) (RR = 9.51, 95% CI = 5.03-17.96), low level of anti mullerian hormone (AMH) (<1 ng/mL) (RR = 14.79, 95% CI = 3.36-66.64), stillbirth (RR = 1.19, 95% CI = 1.02-1.39) and low birth weight (RR = 2.22, 95% CI = 1.55-3.17) were identified. Conversely, no significant results were found in abortion and congenital malformations. CONCLUSIONS: To the best of our knowledge, this is the first meta-analysis assessing the effect of medical radiation on female childhood cancer survivors' reproductive capability and pregnancy outcomes. Although there were some limitations, our meta-analysis further supported that radiotherapy was a risk factor for reproductive health problems of female who survived from childhood cancer.

Ubiquitin­specific protease 22­induced autophagy is correlated with poor prognosis of pancreatic cancer.

Ubiquitin­specific protease 22 (USP22) is a component of the transcription regulatory histone acetylation complex SAGA, which broadly regulates gene transcription and correlates with cancer progression, metastasis and prognosis. Autophagy is a cell pathway with dual functions that promotes cell survival or death. However, it is not known whether USP22 can regulate autophagy in pancreatic cancer. In the present study, we first identified that USP22 was overexpressed in a large number of pancreatic cancer patient samples, concomitant with the increased expression of LC3, a marker of autophagy. Statistical analysis revealed that the increase in USP22 and autophagy was positively correlated with poor prognosis of pancreatic cancer patients. Further investigation using a human pancreatic cancer cell (Panc­1) identified that the overexpression of USP22 increased the processing of LC3 into the active form LC3­II and the number of autophagosomes, thus leading to enhanced autophagy. Activation of ERK1/2 kinase rather than AKT1 by USP22 was found to be one of the mechanisms promoting LC3 processing. USP22­induced autophagy was also found to enhance cell proliferation and resistance to starvation and chemotherapeutic drugs in Panc­1 cells, therefore expressing an overall effect that promotes cell survival. Collectively, the present study demonstrated a new function of USP22 that induces autophagy, thus leading to the poor prognosis of pancreatic cancer.

[Clinical analysis of minimal deviation adenocarcinoma of the cervix: a report of five cases].

BACKGROUND & OBJECTIVE: The minimal deviation adeno-carcinoma (MDA) of the cervix is a rare disease. The misdiagnosis rate of this disease is relatively high and there is no standard treatment for it. This study was to evaluate clinicopathologic features, diagnosis, and treatment of MDA. METHODS: Records of five patients with MDA treated in the Second Affiliated Hospital of Sun Yet-sen University from Jan. 1991 to Dec. 2006 were retrospectively analyzed. RESULTS: The median age of the five patients was 47 years (range 38-59 years). The most common complaints included a large amount of watery discharge and atypical genital bleeding. Histology revealed that MDA was highly differentiated. Although the appearance of MDA glands was difficult to be distinguished from normal endocervical glands, the location of MDA glands was deeper than the lower level of normal endocervical glands. Carcinoembryonic antigen (CEA) and p53 in two patients were detected positive by immunohistochemistry. Four patients underwent surgery, among which one received surgery plus postoperative radiotherapy, and three received surgery plus postoperative chemotherapy and radiotherapy. One inoperable case received palliative radiotherapy. All cases were followed up for 6-88 month. Two patients achieved disease-free survival, one of which survived for more than five years. Three patients died of local recurrence and distant metastasis. CONCLUSIONS: Diagnosis of MDA mainly depends on its clinical manifestations and the pathological feature that MDA glands are located deeper than the lower level of normal endocervical glands. Surgery combined with other adjunct therapy achieves good outcomes for MDA.