Effect of Sequence of Radiotherapy Combined With Immunotherapy on the Incidence of Pneumonitis in Patients With Lung Cancer: A Systematic Review and Network Meta-Analysis.

BACKGROUND: With the widespread application of immune checkpoint inhibitor (ICI) combined with radiotherapy (RT) for the treatment of lung cancer, increasing attention has been paid to treatment-related pneumonitis. The effect of the treatment sequence on the incidence of pneumonitis remains unclear. METHODS: We searched databases including PubMed, Embase, and ClinicalTrials.gov, meeting abstracts, and reference lists of relevant review articles for literature published on radio- and immunotherapy in lung cancer. Stata software (version 16.0) was used for meta-analysis. Data on the incidence of any grade and ≥ grade 3 pneumonitis was pooled using the random effects model. Bayesian network meta-analysis was used for arm-based pairwise comparisons. Subgroup analyses were performed to identify the potential influencing factors. RESULTS: Thirty-eight studies met our inclusion criteria. The network meta-analysis showed no significant difference between the incidence of pneumonitis in concurrent ICI with RT (concurrent arm) and RT followed by ICI (RT-first arm) (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.10-4.81). In the meta-analysis of single group rates, RT following ICI (ICI-first arm) exhibited higher incidence of any grade pneumonitis compared with concurrent- and RT-first arms, with 0.321 (95% CI: 0.260-0.386) for programmed cell death protein 1 (PD-1) inhibitors from clinical trials, and 0.480 (95% CI: 0.363-0.598) for PD-1 inhibitors from real-world retrospective data, respectively. CONCLUSION: No significant difference in the incidence of any grade and grade ≥ 3 pneumonitis was found between RT-first and concurrent arms. The ICI-first arm exhibited a higher incidence of pneumonitis, which needs to be further confirmed by follow-up studies.

Serum ferritin level is an effective prognostic factor for lung cancer immunotherapy.

Immunotherapy of lung cancer has achieved promising clinical results. However, it is urgent to develop predictive biomarkers for effective immunotherapy. While ferroptosis plays a critical role in immunotherapy efficacy, ferritin is an important regulatory factor. We, therefore, hypothesize that basal serum ferritin levels before immunotherapy and their corresponding changes during immunotherapy can be useful predictors of immunotherapy response in patients with lung cancer. We measured serum ferritin levels in 107 patients with lung cancer before and during immune checkpoint blockade treatments and studied the correlation between ferritin levels, response rate, and survival. Moreover, the correlation between basal ferritin and PD-L1 expression, tumor stages and pathological types was also analyzed. Patients with lower basal serum ferritin levels before immunotherapy had longer progression-free survival (PFS) (median 7 vs 4 months, P = .023) and higher disease control rate (DCR) (X2 = 4.837, P = .028), those with downregulated serum ferritin levels during immunotherapy correlated with longer PFS (median 9.5 vs 4 months, P < .001) and higher DCR (X2 = 6.475, P = .011). However, the "integrated factor", which was calculated as the combination of lower basal serum ferritin levels before immunotherapy and downregulated serum ferritin levels during immunotherapy, correlated with prolonged PFS (P < .001). Multivariate analyses revealed that the basal serum ferritin levels before immunotherapy and the corresponding changes during immunotherapy were both strong independent prognostic factors (hazard ratio (HR) = 1.60, P = .041; HR = 2.65, P = .001). These findings suggest that serum ferritin levels can be used as a prognostic biomarker for lung cancer in predicting immunotherapy efficacy.

Chemoradiotherapy combined with immunotherapy in stage III non-small cell lung cancer: a systematic review and meta-analysis of efficacy and safety outcomes.

Background Since the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies. Methods We searched all the relevant studies in PubMed, Embase and Cochrane Library databases. We also reviewed abstracts of relevant conferences, to prevent omissions. The meta-analysis was performed using Stata version 16.0. Results Chemoradiotherapy combined with immunotherapy can improve PFS (HR: 0.60, 95%CI :0.55-0.60) and OS (HR: 0.59, 95%CI :0.53-0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5%-52.7%) and 71.3% (95% CI, 67.3%-75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95%CI, 51.0%-70.3%) and 77.4% (95%CI, 73.2%-81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95%CI, 31.3%-39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95%CI, 31.9%-51.9%). The pooled rate of pneumonitis ≥ grade 3 was 6.7% (95%CI, 5.0%-8.5%). The incidence of pneumonitis ≥ grade 3 after 1 year of immunotherapy is 4.8% (95%CI, 3.1%-6.5%). The incidence of pneumonitis ≥ grade 3 after 2 years of immunotherapy is 5.1% (95%CI, 2.9%-7.3%). Conclusions Prolonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit.

Advances in anti-tumor based on various anaerobic bacteria and their derivatives as drug vehicles.

Cancer therapies, such as chemotherapy and radiotherapy, are often unsatisfactory due to several limitations, including drug resistance, inability to cross biological barriers, and toxic side effects on the body. These drawbacks underscore the need for alternative treatments that can overcome these challenges and provide more effective and safer options for cancer patients. In recent years, the use of live bacteria, engineered bacteria, or bacterial derivatives to deliver antitumor drugs to specific tumor sites for controlled release has emerged as a promising therapeutic tool. This approach offers several advantages over traditional cancer therapies, including targeted drug delivery and reduced toxicity to healthy tissues. Ongoing research in this field holds great potential for further developing more efficient and personalized cancer therapies, such as E. coli, Salmonella, Listeria, and bacterial derivatives like outer membrane vesicles (OMVs), which can serve as vehicles for drugs, therapeutic proteins, or antigens. In this review, we describe the advances, challenges, and future directions of research on using live bacteria or OMVs as carriers or components derived from bacteria of delivery systems for cancer therapy.

Orbital adenoid cystic carcinoma treated by radiotherapy combined with anlotinib in a 13-year-old girl: A case report.

RATIONALE: Adenoid cystic carcinoma (ACC) of orbit is a very rare epithelial tumor, often originating from the lacrimal glands. At the same time, treatment options are currently limited, such as radiation, chemotherapy. We report a case of a patient treated with antirotinib combined with radiotherapy. PATIENT CONCERNS: A 13-year-old girl was initially admitted with "left eye swelling for over half a year, 12 days after surgery for left orbital adenoid cystic carcinoma". Initial swelling of the lateral upper eyelid of the left eye, with gradual enlargement and occasional pain. DIAGNOSES: Left orbital adenoid cystic carcinoma. INTERVENTIONS: After diagnosis of orbital ACC, she underwent resection of the left orbital mass, and received 33 times of adjuvant radiotherapy, but brain metastases appeared later. She refused further treatment, and received 25 times of radiotherapy and anlotinib therapy after the disease progressed again. OUTCOMES: Now the patient has been followed up for 8 months, but no progress was found. LESSONS: Based on this, we hypothesized that radiation therapy in combination with anlotinib is effective for ACC or ACC metastases.

Targeting complement C5a to improve radiotherapy sensitivity in non-small cell lung cancer.

Background: Tumor local and distant relapse recurrence after radiotherapy (RT) is one of the critical factors leading to poor prognosis. The effective antitumor effects of RT are dependent upon the participation of innate and adaptive components of the immune system. C5a/C5aR1 signaling can regulate antitumor immune effect in the tumor microenvironment (TME). Thus, exploring the changes and mechanism in the TME induced by RT-mediated complement activation may provide a novel perspective for reversing radioresistance. Methods: First, fractionated radiation of 8 Gy ×3 fractions were targeted at Lewis lung carcinoma (LLC) tumor-bearing female mice to measure the infiltration of CD8+ T cell and analyze the RNA sequencing (RNA-seq) in RT-recruited CD8+ T cells. Second, tumor growth was measured in LLC tumor-bearing mice treated with RT either with or without C5aR1 inhibitor to clarify the antitumor effect of RT combined with C5aR1 inhibitor. Third, we detected the expression of C5a/C5aR1 and their signaling pathways on radiated tumor tissues. Furthermore, we investigated the expression of C5a in tumor cells at different time points after different doses of RT. Results: In our system, RT induced the increased infiltration of CD8+ T cells and local activation of complement C5a/C5aR. Concurrent administration of RT and blocking of C5aR improved radiosensitivity and tumor-specific immune response, which was reflected by high C5aR expression in CD8+ T cells. The AKT/NF-κB pathway was found to be an important signaling pathway in C5a/C5aR axis mediation by RT. Conclusions: RT promotes the release of C5a from tumor cells and leads to up-regulation of C5aR1 expression via the AKT/NF-κB pathway. Inhibition of the combination of complement C5a and C5aR could improve RT sensitivity. Our work provides evidence that the combination of RT and C5aR blockade opens a new window of opportunity to promote anti-tumor therapeutic effects in lung cancer.

Pseudoprogression during immunotherapy for gastric adenocarcinoma: A case report and literature review.

Immunotherapy is a novel treatment option for various types of cancers. However, the optimal timing for response evaluation has not been well defined. Here, we present a gastric cancer (GC) patient with microsatellite instability-high who experienced recurrence 5 years and 11 months after radical gastrectomy. Then, the patient was treated with radiotherapy, targeted drugs, and immunotherapy. Immunotherapy resulted in 5 months of continuous progression, accompanied by significantly increased tumor marker CA19-9. However, the patient exhibited a satisfactory response without altering the treatment. Based on this, we hypothesized that some persistent progression with elevated tumor markers, known as pseudoprogression (PsP), might be observed in patients with recurrent GC during immunotherapy. This process might be prolonged, but if the treatment is continued, it will eventually produce remarkable therapeutic effects. PsP might challenge the globally accepted immune response evaluation criteria for solid tumors.

Ferritin in cancer therapy: A pleiotropic tumoraffin nanocage-based transport.

BACKGROUND: Ferritin, a ubiquitously distributed iron storage protein, can specifically target tumor cells through transferrin receptor 1. Due to its rearrangeable nanocage structure, ferritin can be loaded with anticancer drugs. Combined with amino acid modifications on the outer- and/or inner-spaces of the nanocage, ferritins can be further coupled with antigens, antibodies, and nucleotide sequences. Since ferritin is naturally presented in the human body, when used in vivo, ferritin exhibits good biocompatibility, and no immunogenic response occurs. These makes ferritin an ideal nanocarrier which shows broad application prospects in cancer therapy. METHODS: In this study, to find articles, a search was made in PubMed with the keywords ferritin, drug delivery, drug delivery, and cancer treatment. RESULTS: According to the investigation, some studies suggest that ferritin can be loaded with drugs and targeted for delivery to tumor tissue. Therefore, ferritin nanocarriers loaded with drugs can be used in chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT) and immunotherapy. Importantly, the specific targeting of ferritin nanocarriers to tumor cells increases the effectiveness of related therapies and reduces side effects. CONCLUSIONS: We conclude in this paper that the superior properties of ferritin nanocarriers as an emerging drug delivery system make them a promising cancer treatment strategy. In the future, it is worth conducting clinical trials to further investigate the safety and efficacy of ferritin nanocarriers in patients.

CGB5, INHBA and TRAJ19 Hold Prognostic Potential as Immune Genes for Patients with Gastric Cancer.

BACKGROUND: Gastric cancer (GC) seriously threatens people's health and life quality worldwide. AIM: The current study sought to explore prognostic immune genes and their regulatory network in GC. METHODS: First, expression data in GC and normal samples were analyzed based on bioinformatics analysis. Immune-related genes were identified and confirmed with univariate/multivariate Cox analysis and receiver-operating characteristic curve. The upstream transcription factors of immune genes were subsequently predicted, and their regulatory network was constructed. GC and adjacent normal tissues were obtained from 76 patients with GC to determine the expression patterns of immune genes and their correlation with overall prognosis. CD8+ T-cell infiltration of patients with high or low risk was detected by means of immunohistochemistry. RESULTS: Bioinformatics analysis highlighted 3689 differentially expressed genes in GC, including 87 immune genes, 8 of which were significantly associated with patient survival. CGB5 and INHBA were high-risk genes, while TRAJ19 was identified as a low-risk gene, all of which were found to be regulated by 11 different transcription factors. Furthermore, CGB5 and INHBA exhibited negative correlation with the prognosis of GC patients; however, TRAJ19 was positively correlated with GC patient prognosis. The incidence of lymph node metastasis was higher, the pathological stage was advanced and the infiltrated CD8+ T cells were fewer in the high-risk GC group. CONCLUSIONS: Overall, our findings identified the key roles of CGB5, INHBA and TRAJ19 in prognosis GC patients, serving as an important gene set for prognostic prediction.

Identification and characterization of stem cells in mammalian esophageal stratified squamous epithelia.

Somatic stem cells are essential for the maintenance of tissue homeostasis. Despite its importance, how the esophageal stratified squamous epithelium executes its self-renewal and maintenance remains elusive. In this study, using 5-bromo-2'-deoxyuridine label-chase in rats in vivo and rat esophageal organoids in vitro together with genome-wide DNA methylation and single-cell RNA sequencing, we identified a slow-cycling/quiescent stem cell population that contained high levels of hemidesmosomes (HDs) and low levels of Wnt signaling localized spatially and randomly at the basal layer of the esophageal epithelium. Pseudotime cell trajectory analysis indicated that tissue cells originated from quiescent basal stem cells in the basal layer. Perturbations of HD component expression and/or Wnt signaling reduced the stem cell population in the basal layer of esophageal keratinocyte organoids, resulting in alterations in the organoid formation rate, size, morphogenesis, and proliferation-differentiation homeostasis. Furthermore, not only high levels of HDs and low levels of Wnt signaling but also an interplay between HD and Wnt signaling defined the stem cells of the basal layer. Hence, HDs and Wnt signaling are critical determinants for defining the stem cells of the basal layer required for tissue homeostasis in mammalian esophagi.

The prognostic value of chemotherapy or/and radiotherapy in adenoid cystic carcinoma and adenoid basal carcinoma of the uterine cervix.

Background: Cervical adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) are rare cervical cancer types and have unclarified clinicopathological features and survival outcomes. This retrospective study focused on predicting the value of radiotherapy or/and chemotherapy for cervical ACC and ABC patients. Methods: The clinical data of cervical ACC and ABC patients in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 and 2013 were included. The clinicopathological features, Kaplan-Meier curves, and overall survival (OS) of patients were evaluated. The prognostic nomogram was established based on the multivariate Cox models. To validate the nomogram prediction, Harrell's Concordance index (C-index) was calculated and receiver operating characteristic (ROC) curves were generated. Results: A total of 84 cervical ACC and 82 ABC patients were identified, and ABC patients had better 10-year OS than ACC patients (60.81% vs. 36.94%, P=0.001). Age, ACC, surgery, radiotherapy, chemotherapy, and regional node involvement were significantly correlated with patient prognosis. In the multivariate analysis, only age >80 years (HR =5.945, 95% CI: 1.912-18.485, P=0.002) and age 70-80 years (HR =4.803, 95% CI: 1.626-14.188, P=0.005) were independent predictors of patient prognosis. In subgroup analysis, patients who underwent surgery (HR =2.199, 95% CI: 1.085-4.455, P=0.029) and the ABC subgroup (HR =4.233, 95% CI: 1.532-11.696, P=0.005) received radiotherapy, chemotherapy, or chemoradiotherapy with a poor prognosis. Patients received radiotherapy (HR =1.936, 95% CI: 1.208-3.105, P=0.006) was associated with a poor prognosis, while surgical patients had a better prognosis (HR =0.535, 95% CI: 0.344-0.832, P=0.006). Conclusions: Cervical ABC patients had a better survival time than cervical ACC patients. We found that increased age was potentially an independent risk factor for poor prognosis, surgical patients had a better prognosis, and radiotherapy, or chemotherapy combination treatment had an unfavorable tendency to prognosis.

Targeting Epithelial-to-Mesenchymal Transition in Radioresistance: Crosslinked Mechanisms and Strategies.

Radiotherapy exerts a crucial role in curing cancer, however, its treatment efficiency is mostly limited due to the presence of radioresistance. Epithelial-to-mesenchymal transition (EMT) is a biological process that endows the cancer cells with invasive and metastatic properties, as well as radioresistance. Many potential mechanisms of EMT-related radioresistance being reported have broaden our cognition, and hint us the importance of an overall understanding of the relationship between EMT and radioresistance. This review focuses on the recent progresses involved in EMT-related mechanisms in regulating radioresistance, irradiation-mediated EMT program, and the intervention strategies to increase tumor radiosensitivity, in order to improve radiotherapy efficiency and clinical outcomes of cancer patients.

PCGF1 is a prognostic biomarker and correlates with tumor immunity in gliomas.

Background: Polycomb group factor 1 (PCGF1) plays a vital role in the self-renewal of cancer stem cells (CSCs). However, the prognostic value and potential function of PCGF1 in glioma progression, especially in tumor immunity, remain unclear. Methods: This study investigated PCGF1 expression in pan-cancers and glioma using The Cancer Genome Atlas Project data, and conducted a logistic regression analysis to analyze the association between PCGF1 expression and the clinicopathological features of glioma patients. Kaplan-Meier and Cox regression analyses were used to assess the prognostic roles of PCGF1. The functional analysis using gene ontology and Kyoto Encyclopedia of Genes and Genomes databases and a gene set enrichment analysis (GSEA) were conducted to examine the PCGF1-related biological processes and signaling pathways. Finally, the roles of PCGF1 in immune infiltration were analyzed by a single sample GSEA (ssGSEA). Results: PCGF1 expression was upregulated in glioma tissues. The high expression of PCGF1 was significantly associated with an age >60 years (P<0.001), an increased World Health Organization grade (P<0.001), and wildtype isocitrate dehydrogenase (IDH) status (P<0.001), and predicted poor overall survival (OS) [hazards ratio (HR) =2.90, 95% confidence interval (CI): 2.25-3.74; P<0.001], the progression-free interval (PFI) (HR =1.99, 95% CI: 1.60-2.46; P<0.001), and disease specific survival (DSS) (HR =2.84, 95% CI: 2.18-3.71; P<0.001). The multivariate regression analysis confirmed that PCGF1 expression was an independent prognostic factor of OS (HR =1.581, 95% CI: 1.161-2.153; P=0.004). Based on the functional enrichment analysis, we identified the PCGF1-related differentially expressed genes (DEGs), and found that PCGF1 was involved in regulating many oncogenic signaling pathways, such as the phosphatidylinositol 3-kinase and protein kinase B pathway, the Janus kinase/signal transducers and activators of transcription (JKT-STAT) signaling pathway, notch signaling and integrin signaling pathway. In addition, we found that PCGF1 expression was positively associated with the abundance of Th2, but negatively associated with T follicular helper, T central memory, and T gamma delta cells. Additionally, PCGF1 participated in the regulation of numerous immune-related processes in glioma. Conclusions: PCGF1 is a promising prognostic biomarker, and as it governs cancer-related pathways and tumor immunity, it plays an important role in glioma development.

Increased risk of ischemic heart disease and diabetes in inflammatory bowel disease.

BACKGROUND: Previous studies showed inconsistent results regarding associations between inflammatory bowel disease (IBD) and risk of ischemic heart disease (IHD) and diabetes. The present study aimed to make a meta-analysis to assess the risk of IHD and diabetes in IBD. METHODS: We searched for articles published before February 2020 in the databases as follows: PubMed, Web of Science, Medline, EMBASE, and Google Scholar. We computed odds ratio (OR) or relative risk (RR) and 95 % confidence intervals (CI) regarding the association between IBD and risk of IHD or diabetes by using STATA 13.0 software. RESULTS: The present meta-analysis showed that IBD was associated with higher risk of IHD (OR/RR = 1.26, 95 % CI 1.20 to 1.32, I2 = 88.3 %, p < 0.0001). Additionally, both ulcerative colitis (UC) and Crohn's disease (CD) were associated with higher risk of IHD (UC: OR/RR = 1.19, 95 % CI 1.13 to 1.26, I2 = 65.6 %, p = 0.001; CD: OR/RR = 1.33, 95 % CI 1.17 to 1.51, I2 = 89.5 %, p < 0.0001). The study showed that IBD was associated with elevated risk of diabetes (OR/RR = 1.26, 95 % CI 1.03 to 1.53, I2 = 92.1 %, I2 = 92.1 %, p < 0.0001). Additionally, both UC and CD were associated with higher risk of diabetes (UC: OR/RR = 1.33, 95 % CI 1.03 to 1.71, I2 = 93.8 %, p < 0.0001; CD: OR/RR = 1.39, 95 % CI 1.10 to 1.76, I2 = 76.7 %, p = 0.002). CONCLUSION: In conclusion, patients with IBD are at increased risk of IHD and diabetes. Thus, regular monitoring of biomarkers of IHD and blood glucose levels should be considered for the early detection of IHD and diabetes in IBD patients.

Effect of galectin-3 on vasculogenic mimicry in esophageal cancer cells.

[This retracts the article DOI: 10.3892/ol.2018.7959.].

Effect of galectin-3 on vasculogenic mimicry in esophageal cancer cells.

Galectin-3 is a multifunctional ß-galactoside binding lectin associated with tumor progression. Previous studies confirmed the roles of galecin-3 overexpression and silencing in the biological behavior of Eca109 human esophageal cancer (EC) cells; galectin-3 may serve a critical role in the vasculogenic mimicry (VM) of tumors. Therefore, the present study examined the effects of galectin-3 knockdown using lentivirus vectors on VM in EC. Eca109 and EC9706 EC cells were transfected with a lentiviral vector to inhibit galectin-3 expression, or a control vector. VM formation in vitro was evaluated via 3D culture. Western blotting was used to detect the expression level of galectin-3 following galectin-3 silencing and the expression levels of VE-cadherin, ephrin type-A receptor 2 precursor (EphA2) and matrix metalloproteinase 2 (MMP-2). According to the results of western blot analysis, the Eca109/galectin-3 and EC9706/galectin-3 cells exhibited effective galectin-3 silencing (P<0.05). Eca109 and EC9706 cells formed typical tubular networks; the number of tubular networks markedly decreased subsequent to galectin-3 knockdown. The expression levels of MMP-2 and EphA2 proteins in Eca109/galectin-3 and EC9706/galectin-3 cells were lower compared with those in Eca109, EC9706, and control vector-transfected Eca109 and EC9706 cells (P<0.05); however, there was no significant difference in the expression of VE-cadherin proteins. These results indicated that galectin-3 may modulate VM in EC by regulating the EphA2 expression level, which affects VM formation via MMP-2.

Clinical Values of Preoperative Use of Antibiotics in Transanal Endoscopic Microsurgery.

OBJECTIVE: To investigate the clinical values of preoperative use of antibiotics in transanal endoscopic microsurgery (TEM). METHODS: Thirty patients undergoing TEM surgery to treat rectal neoplasms in our hospital were selected in this study. All patients were randomly divided into two groups: antibiotic group that antibiotics were used before and after surgery, and control group that antibiotics were only used after surgery. Several markers were evaluated before and after surgery in all patients, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), changes procalcitonin (PCT), white blood cell count (WBC), neutrophils (NE%) and temperature (T). RESULTS: The patients in the antibiotic group at the first and third days after surgery showed lower values of ESR, CRP, WBC, NE% and T than the control group (p < 0.05), furthermore, the WBC and NE% were significantly decreased at the third day after surgery compared with the first day after surgery. For the PCT, there was a significant difference in the first day after surgery between the two groups (p < 0.05), but no significant difference was observed between them at the third day after surgery (p > 0.05). CONCLUSION: The preoperative use of antibiotics in TEM surgery to treat rectal neoplasms may become an effective method to reduce inflammation and prevent infecting after surgery, which will be verified by an amount of studies on large sample.

Pulmonary toxicity generated from radiotherapeutic treatment of thoracic malignancies.

Radiation-induced lung injury (RILI) remains a major obstacle for thoracic radiotherapy for the treatment of lung cancer, esophageal cancer and lymphoma. It is the principal dose-limiting complication, and can markedly impair the therapeutic ratio as well as a patient's quality of life. The current review presents the relevant concepts associated with RILI, including the pathogenic mechanisms and the potential treatment strategies, so as to achieve a general understanding of this issue. RILI comprises an acute radiation pneumonitis phase and subsequent late lung fibrosis. The established assessment criteria are clinical manifestations, imaging changes and the necessity for medical assistance. Risk factors are also considered in order to optimize treatment planning. Due to the underlying molecular mechanisms of RILI, the present review also discusses several targeted pharmacological approaches for its treatment, as well as corticosteroid therapy.

Vasculogenic mimicry is associated with increased tumor-infiltrating neutrophil and poor outcome in esophageal squamous cell carcinoma.

PURPOSE: Vasculogenic mimicry (VM) is known to be a mechanism to nourish the tumor, but little is known about its prognostic significance in esophageal squamous cell carcinoma (ESCC). We characterized the predictive relevance of VM expression and tumor-infiltrating neutrophil (TIN) density in patients with resectable ESCC. METHODS: We retrospectively collected clinicopathologic characteristics of 117 esophageal cancer (EC) patients undergoing complete resection and without preoperative therapy. Immunohistochemistry was used to detect the expression of E-cadherin and CD66b. CD34/periodic acid-schiff (PAS) double staining was used to detect the expression of VM. RESULTS: VM expression was observed in 56 (47.9%) patients. VM was negatively correlated with E-cadherin (correlation coefficient =-0.364, P<0.001) and was positively correlated with infiltration of CD66b neutrophil (correlation coefficient =0.421, P<0.001). VM and CD66b+ neutrophil infiltration are important markers for poor overall survival and disease-free survival. Multivariate analysis showed that VM, CD66b+ neutrophil infiltration, pathologic tumor node metastasis (TNM) (pTNM) stage, and tumor differentiation are significant independent prognostic predictors in ECs (P=0.001, 0.025, 0.001, 0.011, respectively). VM expression is identified in ~47.9% of ESCC, and it is associated with poor outcome and increased TIN. CONCLUSION: TIN is an important factor for VM formation. Therefore, studies of invasive ability of EC in patients with VM could supply significant information for therapeutic strategy.

Novel role of granulocyte-macrophage colony-stimulating factor: antitumor effects through inhibition of epithelial-to-mesenchymal transition in esophageal cancer.

PURPOSE: Recent studies demonstrate the possible antitumor effects of granulocyte-macrophage colony-stimulating factor (GM-CSF); however, the exact mechanism is still unclear. The aim of our study was to analyze the effects of GM-CSF on multiple biological functions of human esophageal cancer (EC) cell lines and to explore the potential mechanism of its antitumor effects. MATERIALS AND METHODS: Eca109/9706 human EC cells were examined. Cell proliferation, apoptosis, and migration were analyzed using cell proliferation assay, flow cytometry, and transwell assay, respectively. The expression of signaling molecules were examined by reverse transcription polymerase chain reaction and Western blot. RESULTS: Our results provide experimental evidence that GM-CSF inhibits growth and migration, as well as induction of apoptosis in EC cells. In addition, EC cells stimulated with GM-CSF were more likely to have suppressed epithelial-to-mesenchymal transition (EMT), accompanied by increased E-cadherin and decreased vimentin expression. CONCLUSION: Our data demonstrate that GM-CSF inhibits cancer cell proliferation and migration, as well as induction of apoptosis. Moreover, our findings indicate that GM-CSF may regulate EMT through JAK2-PRMT5 signaling, and thereby exhibit its antitumor effects on EC cells.