[Chemerin mediated neutrophil infiltration in oral squamous cell carcinoma and predicted poor prognosis].

PURPOSE: To explore the effect of Chemerin in oral squamous cell carcinoma (OSCC) tissue on neutrophils infiltration and its possible molecular mechanism. METHODS: The relationship between Chemerin expression and neutrophils density was assessed via double immunohistochemistry staining.The chemotactic effect of Chemerin on neutrophils in OSCC was detected by transwell assay, real-time quantitative PCR(qRT-PCR), Western blot, enzyme-linked immunosorbent assay(ELISA) and flow cytometry. The data were statistically analyzed using SPSS 23.0 software package. The relationship between Chemerin expression and neutrophils density was assessed using Spearman rank correlation analysis. ChemR23 knockout efficiency and chemotactic index were calculated by ANOVA. The relationship between Chemerin expression, neutrophils density and clinicopathological factors was analyzed by Mann-Whitney test. Kaplan-Meier test and Log rank test were used for survival analysis, and risk factors affecting the survival of OSCC patients was assessed using Cox regression model. RESULTS: Double immunohistochemistry staining showed that overexpression of Chemerin was significantly correlated with increased neutrophils infiltration in OSCC(P=0.023), and strong Chemerin expression and high neutrophils density were associated with higher clinical stage(P＜0.001), cervical lymph node metastasis (P＜0.001) and tumor recurrence (P=0.002). Kaplan-Meier survival analysis showed that patients in the strong Chemerin expression + high neutrophils density group had shortened cancer-related overall survival time and disease-free survival time compared with the other two groups. Transwell assay results showed that both OSCC cells and R-Chemerin had a significant chemotactic effect on dHL-60 cells; knockdown of ChemR23 suppressed Chemerin-induced chemotaxis to dHL-60 cells. CONCLUSIONS: Overexpression of Chemerin in OSCC tissue chemoattracts more neutrophils to tumor sites through its receptor ChemR23 and is related to poor clinical prognosis.

Identification and validation of an immune-related lncRNAs signature to predict the overall survival of ovarian cancer.

Ovarian cancer (OC) is the most lethal gynecological cancer in women. Studies had reported that immune-related lncRNAs signatures were valuable in predicting the survival and prognosis of patients with various cancers. In our study, the prognostic value of immune-related lncRNAs was investigated in OC patients from TCGA-RNA-seq cohort (n=378) and HG-U133_Plus_2 cohort (n=590), respectively. Pearson correlation analysis was implemented to screen the immune-related lncRNA and then univariate Cox regression analysis was performed to explore their prognostic value in OC patients. Five prognostic immune-related lncRNAs were identified as prognostic lncRNAs. Besides, they were inputted into a LASSO Cox regression to establish and validate an immune-related lncRNA prognostic signature in TCGA-RNA-Seq cohort and HG-U133_Plus_2 cohort, respectively. Based on the best cut-off value of risk score, patients were divided into high- and low-risk groups. Survival analysis suggested that patients in the high-risk group had a worse overall survival (OS) than those in the low-risk group in both cohorts. The association between clinicopathological feathers and risk score was then evaluated by using stratification analysis. Moreover, we constructed a nomogram based on risk score, age and stage, which had a strong ability to forecast the OS of the OC patients. The influence of risk score on immune infiltration and immunotherapy response were assessed and the results suggested that patients with high-risk score might recruit multiple immune cells and stromal cells, leading to facilitating immune surveillance evasive. Ultimately, we demonstrated that the risk model was associated with chemotherapy response of multiple antitumor drugs, especially for paclitaxel, metformin and veliparib, which are commonly used in treating OC patients. In conclusion, we constructed a novel immune-related lncRNA signature, which had a potential prognostic value for OC patients and might facilitate personalized counselling for immunotherapy and chemotherapy.

Evaluating the influence of 6MV and 10MV photon beams on cervical cancer volumetric-modulated arc therapy plans.

BACKGROUND: Cervical cancer is a common gynecological cancer among women worldwide. OBJECTIVE: To determine the effects of 6 MV and 10 MV volumetric-modulated arc therapy (VMAT) photon beams on the target volume (TV) planning and critical organs in cases of cervical cancer. METHODS: Fifty patients with carcinoma of the cervix who underwent radiotherapy were selected. The transverse diameter (T) of the cross section of the upper edge of the sacroiliac joint on computerized tomography (CT) images of the patients was measured, and the mean value was calculated as 34 cm. All patients were divided into two groups: Group A (T < 34 cm) and Group B (T > 34 cm). The VMAT plans were generated using 6 MV and 10 MV plans separately. The prescription dose was 47.5 Gy, and the daily dose was 1.9 Gy. RESULTS: In Group A, the planning target volume (PTV) dose assessment parameters of 6 MV and 10 MV plans and their homogeneity and conformity indices were not statistically significantly different. A significant difference was observed between the 6 MV and 10 MV plans for the PTV dose assessment parameters and the homogeneity index of the plans for Group B. The monitor units (MUs) of the 10 MV plans were lower than in the 6 MV plans in both Groups A and B, and the difference was statistically significant. The assessment parameter V40 Gy of both the rectum and bladder in the 6 MV plans was smaller than the corresponding parameter in the 10 MV plans in Group A; in Group B, the assessment parameter V50 Gy of the rectum in the 10 MV plans was smaller than in the 6 MV plans. CONCLUSION: When T < 34 cm, 6 MV energy is more suitable for the external irradiation of cervical cancer. When T > 34 cm, 10 MV energy is more suitable for cervical cancer radiotherapy. Therefore, 10 MV should be considered for patients with a large abdominal size.

Dosimetric analysis of postoperative radiotherapy for thymoma.

PURPOSE: To compare the dosimetric differences between intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) in the treatment of male and female thymoma. MATERIAL AND METHODS: This single-institutional analysis included 20 patients with thymoma treated with RT between January 2017 and December 2020. Twenty patients were retrospectively planned for IMRT (IMRT1 with an average field angle of 216°, 288°, 0°, 72°,and 144°; IMRT2 with fan-shaped field angles of 280°, 320°, 0°, 40°, and 80°) and VMAT (VMAT1 with two arcs ranging form 280° to 80°,clockwise and then counterclockwise; VMAT2 with two 360° arcs). The plans for all investigated RT modalities were optimized for a prescriptional dose of 50Gy and fractional dose of 2.0Gy. Planning target volume (PTV) and organs-at-risk (OARs: heart, breasts, lungs, spinal cord, and esophagus) dosimetric parameters were compared. RESULTS: All plans met the preparation aims for all the included metrics. There was little difference in the median values of PTV parameters (D2%, D98%, Dmean, homogeneity index[HI], and conformity index [CI]). The CI of the VMAT2 plan was the closest to 1 in both therapy groups. The monitor unit (MU) of IMRT2 and the estimated total delivery time of VMAT1 were the lowest in both therapy groups and were statistically significant. In the male group, the lung parameters (Dmean, V5Gy, V10Gy, and V20Gy) for VMAT1 were the lowest and showed statistical significance. In the female group, the lung parameters (Dmean, V5Gy, V10Gy, and V20Gy) and bilateral breast parameters (Dmean, V5Gy, V10Gy, and V20Gy) of IMRT2 were the lowest and showed statistical significance. CONCLUSIONS: In male thymoma patients undergoing postoperative RT (PORT) treatment, the choice of fan-shaped VMAT may be a better option for protecting the lungs. For female thymoma patients receiving PORT, fan-shaped IMRT can better protect the lungs and breasts. The fan-shaped field performed better than the average and the full arc fields in PORT for thymoma.

Horseshoe kidney with PLA2R-positive membranous nephropathy.

BACKGROUND: Horseshoe kidney (HSK) is a common congenital defect of the urinary system. The most common complications are urinary tract infection, urinary stones, and hydronephrosis. HSK can be combined with glomerular diseases, but the diagnosis rate of renal biopsy is low due to structural abnormalities. There are only a few reports on HSK with glomerular disease. Here, we have reported a case of PLA2R-positive membranous nephropathy occurring in a patient with HSK. CASE PRESENTATION: After admission to the hospital due to oedema of both the lower extremities, the patient was diagnosed with nephrotic syndrome due to abnormal 24-h urine protein (7540 mg) and blood albumin (25 g/L) levels. Abdominal ultrasonography revealed HSK. The patient's brother had a history of end-stage renal disease due to nephrotic syndrome. Therefore, the patient was diagnosed with PLA2R-positive stage II membranous nephropathy through renal biopsy under abdominal ultrasonography guidance. He was administered adequate prednisone and cyclophosphamide, and after 6 months of treatment, urinary protein excretion levels significantly decreased. CONCLUSION: The risk and difficulty of renal biopsy in patients with HSK are increased due to structural abnormalities; however, renal biopsy can be accomplished through precise positioning with abdominal ultrasonography. In the literature, 20 cases of HSK with glomerular disease have been reported thus far. Because of the small number of cases, estimating the incidence rate of glomerular diseases in HSK is impossible, and the correlation between HSK and renal pathology cannot be stated. Further studies should be conducted and cases should be accumulated to elucidate this phenomenon.

Radiation enhancing effects with the combination of sanazole and irinotecan in hypoxic HeLa human cervical cancer cell line.

PURPOSE: This study was conducted to determine the synergistic radiation sensitizing effects of the combination of sanazole and irinotecan in hypoxic cervical cancer HeLa human tumor cell line. METHODS: The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to evaluate the number of surviving cells. Cell cycle was determined by flow cytometry. Surviving cell fractions were determined by the standard in vitro colony formation assay. RESULTS: The MTT assay showed that the presence of irinotecan with or without sanazole reduced significantly the cells' viability. Flow cytometry demonstrated that the combination of sanazole and irinotecan led to more HeLa cells blocked in G(2) phase. Cell colony formation assay indicated that the radiosensitivity of hypoxic HeLa cells was enhanced by sanazole and/or irinotecan. CONCLUSION: This study showed that the radiation enhancing effects produced by the combination sanazole and irinotecan was significant in hypoxic HeLa cells, which were arrested in the G(2) phase of the cell cycle. This study may provide a new combination modality of radiosensitizers in the radiotherapy of cervical cancer.

[Application of simplified intensity modulated radiation therapy in gastric cancer after operation].

OBJECTIVE: To elucidate the application and the dosimetry characteristic of the simplified intensity modulated radiation therapy (sIMRT) for gastric cancer after operation, and to compare the dose distribution with intensity modulated radiation therapy (IMRT) and three-dimension conformal radiation therapy (3D-CRT). METHODS: Twelve patients with gastric cancer after operation were enrolled in this study. 3D-CRT plan, 5-field IMRT plans (20 degree, 80 degree, 180 degree, 280 degree, 340 degree) and 5-field sIMRT plans (20 degree, 80 degree, 180 degree, 280 degree, 340 degree) were performed for each patient. The conformal index (CI), heterogeneity index (HI) of the planning target volume (PTV) and the dose of normal organs were analyzed with the dose volume histogram (DVH). The total MU and treatment time were also compared. RESULTS: The sIMRT and IMRT plans had comparable CI (sIMRT>IMRT>3D-CRT), and showed better dose conformity but worse homogeneity than 3D-CRT. The percentage of volume receiving 20 Gy, 25 Gy, 30 Gy and 40 Gy by liver were significantly lower in sIMRT than that in 3D-CRT, and comparable to IMRT. All the dose volumes to kidneys with sIMRT were still significantly lower as compared to 3D-CRT, and comparable to IMRT. The sIMRT plan was better than IMRT plan in total MU and treatment time. CONCLUSIONS: sIMRT has comparable dose distribution in patients with gastric cancer to IMRT, but is significantly better than 3D-CRT. Treatment time of sIMRT is the shortest. So sIMRT technique can be applied more simply.

C-reactive protein level predicts prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy.

The aim of this study was to investigate the effect of C-reactive protein (CRP) level on the prognosis of patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy. Fifty-seven patients with locoregionally advanced laryngeal carcinoma (cT3-4, N0-3, M0) treated with chemoradiotherapy were reviewed retrospectively. Chemoradiotherapy comprised external beam radiotherapy to the larynx (70 Gy) with three cycles of cisplatin at 3-week intervals. Elevated CRP was defined as >8 mg/L. The survival rate was calculated using the Kaplan-Meier method, and a multivariate analysis was used to identify significant factors associated with prognosis, using a Cox proportional hazards model. During the median (range) follow-up of 5 years (1.3-5), 29 patients died from laryngeal cancer; the 5-year cancer-specific survival (CSS) rate was 49.12%. Fifteen patients had a high CRP level before chemoradiotherapy (>8 mg/L), and their CSS rate was significantly worse than that in the remaining patients (P = 0.003). Multivariate analysis showed that CRP and tumor site were independent prognostic indicators for CSS, with a hazard ratio of 2.66 (95% confidence interval (CI), 1.22-5.82; P = 0.014) and a hazard ratio of 1.67 (95% CI, 1.01-2.77; P = 0.045), respectively. Of those with elevated CRP, the CRP levels of ten patients became normal after chemoradiotherapy, of whom four were alive with no evidence of recurrence or metastasis during the follow-up. By contrast, all six with no CRP normalization after chemoradiotherapy died within 3.8 years. The elevation of CRP before treatment predicts a poor prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy.

Effect of antisense oligonucleotides to nuclear factor-kappaB on the survival of LPS-induced ARDS in mouse.

Because nuclear factor (NF)-kappaB-regulated cytokines, including tumor necrosis factor-alpha (TNF-alpha), from monocytes and macrophages have been implicated in the pathogenesis and development of septic shock and acute respiratory distress syndrome (ARDS), the effect of the antisense oligonucleotide to the p65 subunit of NF-kappaB on the survival of lipopolysaccharide (LPS)-induced ARDS in BALB/c mice was examined. None and 70% of the animals died of diffuse hemorrhagic lung edema 1 to 2.5 days after intraperitoneal administration of 10 and 20 mg/kg LPS alone, respectively. Intravenously administered antisense oligonucleotide alone did not produce any significant changes in the behavior or lung histology. After intravenous administration of the anti-sense oligonucleotide, both peripheral blood monocytes and alveolar macrophages in bronchoalveolar lavage fluid were confirmed to contain sufficiently large amounts of intracellular antisense oligonucleotides for their function usingfluorescein isothiocyanate (FTCC)-labeled microscopy. The antisense oligonucleotide administered 6 hours before the intraperitoneal administration of LPS significantly decreased the survival rate with the progress of hemorrhagic edema in lung histology; 90% and 100% of animals treated with the antisense oligonuleotide died 0.5 to 1.5 days after the administration of 10 and 20 mg/kg LPS, respectively. These findings suggest that the suppression of cytokines and mediators in monocytes and alveolar macrophages by the antisense oligonucleotide to the p65 subunit of NF-kappaB worsens the survival of LPS-induced ARDS in mice with the progress of hemorrhagic lung edema.