Research progress and treatment of radiation enteritis and gut microbiota

Radiation enteritis is a kind of intestinal radiation injury in patients with pelvic and retroperitoneal malignancies after radiotherapy, and its occurrence and development process are very complicated. At present, studies have confirmed that intestinal microecological imbalance is an important factor in the formation of this disease. Abdominal radiation causes changes in the composition of the flora and a decrease in its diversity, which is mainly manifested by a decrease in beneficial bacterial species such as Lactobacilli and Bifidobacteria. Intestinal dysbacteriosis aggravates radiation enteritis, weakens the function of the intestinal epithelial barrier, and promotes the expression of inflammatory factors, thereby aggravating the occurrence of enteritis. Given the role of the microbiome in radiation enteritis, we suggest that the gut microbiota may be a potential biomarker for the disease. Treatment methods such as probiotics, antibiotics, and fecal microbiota transplantation are ways to correct the microbiota and may be an effective way to prevent and treat radiation enteritis. Based on a review of the relevant literature, this paper reviews the mechanism and treatment of intestinal microbes in radiation enteritis.

Radiotherapy combined with immunotherapy could improve the immune infiltration of melanoma in mice and enhance the abscopal effect

Purpose@#To analyze the gene mutation, immune infiltration and tumor growth of primary tumor and distant tumor under different treatment modes. @*Materials and Methods@#Twenty B16 murine melanoma cells were injected subcutaneously into the of both sides of the thigh, simulating a primary tumor and a secondary tumor impacted by the abscopal effect, respectively. They were divided into blank control group, immunotherapy group, radiotherapy group, and radiotherapy combined immunotherapy group. During this period, tumor volume was measured, and RNA sequencing was performed on tumor samples after the test. R software was used to analyze differentially expressed genes, functional enrichment, and immune infiltration. @*Results@#We found that any treatment mode could cause changes in differentially expressed genes, especially the combination treatment. The different therapeutic effects might be caused by gene expression. In addition, the proportions of infiltrating immune cells in the irradiated and abscopal tumors were different. In the combination treatment group, T-cell infiltration in the irradiated site was the most obvious. In the immunotherapy group, CD8+ T-cell infiltration in the abscopal tumor site was obvious, but immunotherapy alone might have a poor prognosis. Whether the irradiated or abscopal tumor was evaluated, radiotherapy combined with anti-programmed cell death protein 1 (anti-PD-1) therapy produced the most obvious tumor control and might have a positive impact on prognosis. @*Conclusion@#Combination therapy not only improves the immune microenvironment but may also have a positive impact on prognosis.

TUT4 affects the radiosensitivity of esophageal epithelial cells by regulating the uridylation of miR132/212 clusters / 中华放射医学与防护杂志

Objective:To validate the effect of TUT4 on the radiosensitivity of esophageal epithelial cells (HEEC) by regulating the uridylation of miR132/212 clusters.Methods:The expression of TUT4 in HEEC at 0, 6, 18, 24 and 48 h after 0, 2, 4, 6 and 8 Gy X-ray irradiation was detected by PCR. The HEEC cells were divided into four groups: NC group, shTUT4 group, 6 Gy group, and 6 Gy+ shTUT4 group. The effects of TUT4 on cell radiosensitivity, cell proliferation, cell cycle, mitochondrial damage, and oxygen free radical production were detected respectively. The effect of down-regulated TUT4 expression on miR132/212 uridylation was detected by RT-PCR, and the radiosensitivity of HEEC with overexpression of miR132/212 or miR132/212+ UUU was detected by clone formation and proliferation assay, respectively. Proliferation assay was performed to detect the proliferation of HEEC when TUT4 expression was down-regulated and miR132/212 or miR132/212+ UUU was overexpressed.Results:TUT4 expression increased after different doses of X-ray irradiation ( t=12.84, 62.06, 27.86, 32.43, P<0.05). Downregulation of TUT4 expression increased the radiosensitivity of HEEC ( t=13.2, 5.85, 7.31, P<0.05) with a SER D0of 1.41 and D0=0.79, Dq=1.61, SF2=0.47. Compared with 6 Gy group, cell proliferation in 6 Gy+ shTUT4 group was decreased ( t=7.12, 13.63, P<0.05), cells in S phase were increased ( t=11.98, P<0.05), mitochondrial damage was increased ( t=11.98, P<0.05), and ROS level was increased ( t=15.65, P<0.05). Down-regulation of TUT4 expression increased miR132/212 expression and decreased miR132/212+ UUU expression ( t=27.90, 60.99, P<0.05). Overexpression of miR132/212 increased the radiosensitivity of HEEC, and overexpression of miR132/212+ UUU decreased the radiosensitivity of HEEC, with SER D0 of 1.20 and 0.71, respectively. Cell proliferation of shTUT4 + miR132/212 group waslower than that of shTUT4 group( t=4.76, 7.65, P<0.05), and cell proliferation of shTUT4 + miR132/212+ UUU group was higher than that of shTUT4 ( t=7.22, P<0.05). Conclusions:X-ray irradiation increased the expression of TUT4 in HEEC, and the down-regulation of TUT4 reduced HEEC radiosensitivity and radiation damage, where the uridylation of miR132/212 was involved in.

Prognostic value of serum P-cadherin level in patients with non-small cell lung cancer / 国际肿瘤学杂志

Objective To investigate the prognostic value of serum P-cadherin( P-cad)level in patients with non-small cell lung cancer(NSCLC). Methods A total of 80 patients with NSCLC in Hanzhong 3201 Hospital of Shaanxi Province from January 2012 to December 2013 were selected as study subjects. The relationships between serum P-cad level and clinicopathological characteristics were analyzed. The Cox regres-sion analysis was used to analyze the risk factors affecting prognosis of NSCLC patients. The survival curve was drawn by Kaplan-Meier method and the difference test was carried out by log-rank method. Results There were significant differences in lymph node metastasis(χ2 = 14. 31,P < 0. 001),vascular invasion(χ2 = 5. 56, P = 0. 018)among NSCLC patients with different levels of serum P-cad. Multivariate Cox regression analysis showed that lymph node metastasis(HR = 0. 856,95％ CI:0. 702-0. 955,P = 0. 012),TNM stage(ⅢA HR =1. 315,95％ CI:1. 058-1. 991,P = 0. 024;ⅢB HR = 1. 448,95％ CI:1. 124-2. 215,P = 0. 011;Ⅳ HR =1. 569,95％ CI:1. 182-2. 441,P < 0. 001)and high level of serum P-cad(HR = 1. 815,95％ CI:1. 224-3. 562,P < 0. 001)were risk factors for progression-free survival in NSCLC patients,and lymph node metasta-sis(HR = 0. 755,95％ CI:0. 652-0. 915,P = 0. 022),poor differentiation(HR = 1. 622,95％ CI:1. 112-2. 015,P < 0. 001),TNM stage(ⅢA HR = 1. 335,95％ CI:1. 064-2. 014,P = 0. 011;ⅢB HR = 1. 489, 95％ CI:1. 129-2. 297,P < 0. 001;Ⅳ HR = 1. 622,95％ CI:1. 192-2. 501,P < 0. 001)and high level of serum P-cad(HR = 1. 677,95％ CI:1. 193-2. 668,P < 0. 001)were risk factors for overall survival of NSCLC patients. The results of Kaplan-Meier survival curve showed that the overall survival and progression-free survival of patients with high level of serum P-cad were shorter than those of patients with low level of serum P-cad(χ2 = 5. 18,P = 0. 015;χ2 = 5. 48,P = 0. 011). Conclusion High level of serum P-cad is closely related to poor prognosis in NSCLC patients.

Comparison of radiotherapy alone versus concurrent chemoradiotherapy in the treatment of elderly esophageal cancer / 中华放射医学与防护杂志

Objective To compare the prognostic factors and adverse effects of elderly patients with esophageal cancer between radiotherapy alone and concurrent chemoradiotherapy. Methods A total of 479 patients with esophageal squamous cell carcinoma aged 70 years or older were analyzed retrospectively at our institute, from January 2008 to December 2017. The patients were divided into radiotherapy alone group ( 359 cases ) and concurrent chemoradiotherapy group ( 120 cases ) . After Propensity Score Matching ( PSM) , data from matched patients with 102 cases in each group was analyzed. The overall survival (OS) rates, the prognostic factors and adverse effects were assessed. Results The 1, 3, 5-year of OS in radiotherapy alone group after PSM were 77. 4％, 40. 1％, 22. 7％, respectively, and median overall survival time (mOS) was 26. 9 months (95％ CI:18. 7 - 35. 2 months). The chemoradiotherapy group after PSM were 79. 5％, 47. 6％, 35. 7％ and 35. 6 months (95％ CI:23. 2-48.0 months), respectively, while there was no significant difference between the groups (P >0. 05). Subgroup analysis showed that the 1, 3, 5-year of OS and mOS of the patients aged 70 -75 years in radiotherapy alone group were 79. 4％, 41. 0％, 26. 2％ and 29. 2 months, respectively. The patients aged 70-75 years in chemoradiotherapy group were 86. 5％, 56. 1％, 47. 6％ and 48. 9 months, respectively. There was statistically significance between the groups after PSM(χ2 =4. 746, P<0. 05). The univariate prognostic analysis showed that the age, T stage, N stage, clinical stage, short-term efficacy and performance status were influencing factors for OS (χ2 =6. 714-42. 900, P<0. 05). The clinical stage and short-term efficacy were independent prognostic factors for OS (χ2 =5. 007 -9. 181, P<0. 05). In addition , the risk of non-tumor related death of the patients aged 75 years or older in the chemoradiotherapy group was higher than those in the radiotherapy alone group(χ2 =5. 630, P<0. 05). The prevalence of toxicities (≥grade 3) including bone marrow suppression, radiation esophagitis and radiation pneumonia in the chemoradiotherapy group were higher than that in the radiotherapy alone group (χ2 =4. 701 -28. 318, P<0. 05). Conclusions Concurrent chemoradiotherapy, compared with radiotherapy alone, may improve the prognosis of patients aged 70-75 years with esophageal squamous cell carcinoma.

Long-term efficacy of neoadjuvant chemotherapy followed by intensity-modulated radiation therapy on 96 cases of locally advanced nasopharyngeal carcinoma / 实用医学杂志

Objective To observe the long?term efficacy of neoadjuvant chemotherapy followed by intensity?modulated radiation therapy. Methods A retrospective analysis was performed on the data of 183 patients with locally advanced NPC who were hospitalized in our hospital:96 cases in the observation group, 87 cases in the con?trol group. Results There were no significant differences between the observation group and the control group in terms of five?year OS (77.1%vs. 78.2%, P=0.861), DMFS(89.6%vs. 90.8%, P=0.782), RFS (78.1%vs. 77%, P=0.857) and PFS (72.9%vs. 71.3%, P=0.803). Compared with the control group, the observation group did not sig?nificantly improve 5?year OS, DMFS, RFS and PFS in T3?4N0?1 patients and also did not improve 5?year OS, DMFS, RFS and PFS in T1?4N2?3 patients. There were significantly larger numbers of individuals with adverse reactions in the observation group than in the control group. Conclusions Compared with the long?term efficacy in the patients with locally advanced NPC between neoadjuvant chemotherapy followed by intensity?modulated radiation therapy with concurrent chemotherapy and intensity?modulated radiation therapy with concurrent chemotherapy, the progno?sis has no significantly differences and neoadjuvant chemotherapy followed by intensity?modulated radiation therapy with concurrent chemotherapy leads to a larger number of adverse reactions. The action of neoadjuvant chemothera?py followed by intensity?modulated radiation therapy with concurrent chemotherapy in treatment of locally advanced NPC needs more research.

Dihydroartemisinin induces radiosensitivity in cervical cancer cells by modulating cell cycle progression

To investigate the radiosensitizing effects of dihydroartemisinin [DHA] and its underlying mechanisms in cervical cancer cells. This experimental study was conducted between May 2009 and August 2012 in the School of Radiation Medicine and Protection, Soochow University, Suzhou, China. HeLa and Siha cells were assigned as the control group and DHA as treated group. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-2H-tetrazolium bromide [MTT] assay, clonogenic assay, cell cycle analysis, and apoptosis analysis were carried out in 2 cell lines of both groups. The inhibitory effect of DHA on the HeLa and Siha cell lines was dependent on both concentration and time. Dihydroartemisinin increased the radiosensitivity of HeLa cells, but not of Siha cells. Apoptosis and the gap2/mitosis [G2/M] phase transition induced by x-irradiation was enhanced by DHA treatment in HeLa cells. Irradiation, combined with DHA, decreased Wee1 expression while increasing Cyclin B1 expression in HeLa cells. Dihydroartemisinin potently abrogates G2 checkpoint control in HeLa cells. It can relieve the G2/M arrest induced by irradiation; thus, it can be used as an effective radiosensitizer, which will probably promote the entry of more irradiation-damaged cells into mitosis

Radiosensitizing effect of artesunate on nude mice transplanted with HeLa cells of cervical cancer / 中华放射医学与防护杂志

Objective To investigate the radiosensitization of artesunate on nude mouse transplanted with HeLa cells,and to explore its possible mechanisms.Methods HeLa cells were inoculated into the nude mice to establish tumor model.Mice were randomly divided into 4 groups as blank control,artesunate group,radiation group and artesunate + radiation group when average volume of tumor were about 5 mm × 5 mm× 5 mm.During the term of treatment,the volume of tumors were measured every 2days.After 14 days treatment,the mice were killed and tumor tissues were harvested for flow cytometry to detect the alteration of cell cycle.Meanwhile,the pathological change of the tumor tissue was observed with HE staining method,and the change of expression of cycle regulatory protein Cyclin B1,Cdc2 and Wee1 were detected by Western blot.Results The growth of tumor was significantly inhibited by artesunate combined with radiation and its inhibition rate was 72.34％.Flow cytometry results showed that the percent of cells in G1 phase increased and G2 phase decreased in the artesunate + radiation group compared with those in irradiation group ( t =4.41,4.12,P ＜ 0.05 ).The expression level of Cyclin B1 was obviously increased while that of Wee1 decreased in the artesunate + radiation compared with irradiation group.There was no difference in the expression of Cdc2 among the four groups.Conclusions Artesunate can dramatically increase the radiosensitivity of transplanted tumor of HeLa cells.The possible mechanism might be related to the decreasing G2 phase by regulating the expression of Cyclin B1 and Wee1.