Prognostic value of post-radiotherapy neutrophil-to-lymphocyte ratio in locally advanced nasopharyngeal carcinoma.

PURPOSE: To explore the temporal profile of the peripheral neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced nasopharyngeal carcinoma (LANPC) and the potential prognostic value of its dynamic changes. METHODS: Complete blood count of 112 patients from a previous phase II study were retrospectively collected at the timepoints of the initiation of induction chemotherapy (pre-IC), within 1 week before radiotherapy started (pre-RT), and within 1 week after radiotherapy finished (post-RT). Data of 103 patients were fully recorded and Cox regression analysis was used to analyze the correlations of potential risk factors with 5­year overall survival (OS). The performance of the prognostic factor was validated in another independent cohort of 103 matched (by T and N stage) patients selected from 236 consecutive NPC patients treated with IC and concurrent chemoradiation. RESULTS: Multivariate analysis (MVA) identified patient age >50 years old (hazard ratio [HR] = 3.4, p = 0.02), weight loss during RT >7.5% (HR = 3.2, p = 0.03), and post-RT peripheral NLR >7.05 (vs. NLR ≤7.05, HR = 2.5, p = 0.04, 5­year OS 71.4% vs. 87.8%) as unfavorable prognostic factors for OS. There was also a non-significant trend in the MVA that patients with post-RT peripheral NLR >7.05 showed worse progression-free survival (PFS; HR = 1.9, p = 0.06, 5­year PFS 64.1% vs. 81.8%). Post-RT NLR had a good prognostic performance in the validation cohort (concordance index = 0.73, standard error 0.10; p = 0.02, Wilcoxon test). CONCLUSION: Post-RT NLR is an independent prognostic factor for OS in LANPC patients. The dynamic change of the routinely tested inflammatory variable could help selection of appropriate treatment options and follow-up strategies.

ADST: Forecasting Metro Flow Using Attention-Based Deep Spatial-Temporal Networks with Multi-Task Learning.

Passenger flow prediction has drawn increasing attention in the deep learning research field due to its great importance in traffic management and public safety. The major challenge of this essential task lies in multiple spatiotemporal correlations that exhibit complex non-linear correlations. Although both the spatial and temporal perspectives have been considered in modeling, most existing works have ignored complex temporal correlations or underlying spatial similarity. In this paper, we identify the unique spatiotemporal correlation of urban metro flow, and propose an attention-based deep spatiotemporal network with multi-task learning (ADST-Net) at a citywide level to predict the future flow from historical observations. ADST-Net uses three independent channels with the same structure to model the recent, daily-periodic and weekly-periodic complicated spatiotemporal correlations, respectively. Specifically, each channel uses the framework of residual networks, the rectified block and the multi-scale convolutions to mine spatiotemporal correlations. The residual networks can effectively overcome the gradient vanishing problem. The rectified block adopts an attentional mechanism to automatically reweigh measurements at different time intervals, and the multi-scale convolutions are used to extract explicit spatial relationships. ADST-Net also introduces an external embedding mechanism to extract the influence of external factors on flow prediction, such as weather conditions. Furthermore, we enforce multi-task learning to utilize transition passenger flow volume prediction as an auxiliary task during the training process for generalization. Through this model, we can not only capture the steady trend, but also the sudden changes of passenger flow. Extensive experimental results on two real-world traffic flow datasets demonstrate the obvious improvement and superior performance of our proposed algorithm compared with state-of-the-art baselines.

In vitro and in vivo evaluation of chitosan scaffolds combined with simvastatin-loaded nanoparticles for guided bone regeneration.

The objective of this study was to fabricate and characterize chitosan combined with different amounts of simvastatin-loaded nanoparticles and to investigate their potential for guided bone regeneration in vitro and in vivo. Different SIM-CSN formulations were combined into a chitosan scaffold (SIM-CSNs-S), and the morphology, simvastatin release profile, and effect on cell proliferation and differentiation were investigated. For in vivo experiments, ectopic osteogenesis and the critical-size cranial defect model in SD rats were chosen to evaluate bone regeneration potential. All three SIM-CSNs-S formulations had a porous structure and exhibited sustained simvastatin release. CSNs-S showed excellent degradation and biocompatibility characteristics. The 4 mg SIM-CSNs-S formulation stimulated higher BMSC ALP activity levels, demonstrated significantly earlier collagen enhancement, and led to faster bone regeneration than the other formulations. SIM-CSNs-S should have a significant effect on bone regeneration.

Radiological-pathological correlation of yolk sac tumor in 20 patients.

BACKGROUND: Yolk sac tumor (YST) is a rare tumor. Familiarity of its radiological characteristics may permit preoperative diagnosis and improve surgical management of patients. However, a detailed description of the imaging features of YST with pathological correlation in particular is scarce. PURPOSE: To investigate computed tomography (CT) findings of YSTs with pathological correlation. MATERIAL AND METHODS: CT images of 20 patients with pathologically proven YST were retrospectively reviewed. The location, size, margin, internal architecture, and pattern and degree enhancement of the lesion were evaluated. Radiological findings were correlated with pathological results. RESULTS: The locations of 20 tumors were distributed between the testis (n = 3), ovary (n = 6), sacrococcygeal area (n = 6), rectum (n = 1), and mediastinum (n = 4). The median age was 13 years. On CT images, all tumors were seen as oval (n = 14) or irregular (n = 6), well-defined (n = 16) or ill-defined (n = 4) masses with a mean size of 9.7 cm. The lesions were solid cystic (n = 10), entirely solid (n = 6), or predominantly cystic (n = 4). Intratumoral hemorrhage, calcification, and fatty tissue were seen in nine, three, and two tumors, respectively. Discontinuity of the tumor wall was seen in eight tumors. After contrast media administration, most tumors showed heterogeneous moderate to marked enhancement (n = 7) or heterogeneous marked enhancement (n = 9). Enlarged intratumoral vessels were seen in 17 tumors. CONCLUSION: YST usually appears as a large solid-cystic mass with intratumoral hemorrhage, capsular tear, marked heterogeneous enhancement, and enlarged intratumoral vessels on CT images. Intratumoral calcification and fatty tissue, although rare, may indicate a mixed YST containing teratoma component.

Biomimetic remineralization of demineralized enamel with nano-complexes of phosphorylated chitosan and amorphous calcium phosphate.

Remineralization of enamel plays a crucial role in the progression of carious process and the management of early caries lesion. Based on the influence of phosphorylated proteins in biomineralization, the objective of this study was to synthesize nano-complexes of phosphorylated chitosan and amorphous calcium phosphate (Pchi-ACP), and evaluate their ability to remineralize enamel subsurface lesions in vitro. Pchi was synthesized using a previously established chemical method. The biomimetic remineralizing solution containing nano-complexes of Pchi-ACP was prepared by adding CaCl2 and K2HPO4 into Pchi-ACP solution (0.5 % w/v) in sequence. The final concentrations of calcium and phosphate ions were 10 and 6 mM, respectively. The nano-complexes of Pchi-ACP were characterized by Fourier-transform infrared (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). During testing the enamel lesions were treated with Pchi-ACP and fluoridated remineralizing solutions, respectively. The remineralizing of enamel lesions was examined with field emission electron microscope (FE-SEM) and Micro-CT. ACP was stabilized by Pchi to form nano-complexes that were soluble in water. The size of Pchi-ACP nano-complexes particles was determined to be less than 50 nm. XRD and SAED results confirmed their amorphous phases. FE-SEM and Micro-CT results showed that the remineralizing effect of Pchi-ACP on enamel lesions was similar to that of fluoride. However, the remineralizing rate of Pchi-ACP treatment was significantly higher than that of fluoride treatment (P < 0.05). This study highlighted the potential of nanoparticles functionalized with a natural analogue involved in biomineralization, to remineralize early enamel caries.

Ten years' experience with needle biopsy in the early diagnosis of sacroiliitis.

OBJECTIVE: To evaluate the usefulness of needle biopsy in the diagnosis of early sacroiliitis to improve the diagnostic level and outcome of ankylosing spondylitis (AS). METHODS: One hundred nine patients in whom early AS was highly suspected, but in whom only sacroiliitis of grade I or lower on radiography/computed tomography (CT) was seen, were recruited for study. CT-guided needle biopsy of the sacroiliac joints was performed, and the patients were followed up for 5-10 years. RESULTS: Of the 109 patients, magnetic resonance imaging (MRI) was used to confirm the presence or absence of sacroiliitis in 77 patients. Of these, 23 patients were determined to have sacroiliitis on MRI, and 54 had no sacroiliitis on MRI. Needle biopsy was performed on all 109 patients. Features of inflammation were found in 85 patients, which included all 23 patients with MRI evidence of sacroiliitis and 38 of the 54 patients without MRI evidence of sacroiliitis. No features of inflammation were found on needle biopsy in 24 of the patients, including the remaining 16 patients who did not have sacroiliitis on MRI. The sensitivity and specificity of MRI for the early diagnosis of sacroiliitis in these patients were 37.7% and 100%, respectively. Thirty-four patients with pathologic evidence of sacroiliitis were followed up for 5-10 years. At the study end point, 16 of these 34 patients continued to show grade I or lower changes on CT, and 18 had changes of grade II or higher. These 18 patients included 7 of the 8 patients with evidence of sacroiliitis on MRI and 6 of the 20 patients confirmed not to have MRI evidence of sacroiliitis at baseline. CONCLUSION: MRI, though of low sensitivity, is specific for the diagnosis of early sacroiliitis. Sacroiliitis can be detected earlier by needle biopsy than by MRI.

Correlation between expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 and cervical lymph node metastasis of nasopharyngeal carcinoma.

OBJECTIVES: We evaluated the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-2 (MMP-2) in nasopharyngeal carcinoma (NPC) and studied their relationship with cervical lymph node metastasis. METHODS: Immunohistochemical staining was used to detect the expression of EMMPRIN and MMP-2 in specimens from patients with chronic nasopharyngitis (CN), nonmetastastic NPC (NM-NPC), and lymph node-metastatic NPC (LNM-NPC). RESULTS: The rates of positive EMMPRIN expression in CN, NM-NPC, and LNM-NPC were 13.3%, 30.0%, and 66.7%, respectively. Significant differences were found between the rates in CN and LNM-NPC (p <0.01) and between the rates in NM-NPC and LNM-NPC (p = 0.01). In the LNM-NPC group, NPC cells had a higher rate of expression of EMMPRIN in tumor metastases than in the primary tumor (81.8% versus 66.7%; p = 0.01). The rates of positive MMP-2 expression in CN, NM-NPC, and LNM-NPC were 13.3%, 35.0%, and 60.6%, respectively. A significant difference was found between the rates in CN and LNM-NPC (p < 0.01). In the LNM-NPC group, NPC cells had a higher rate of MMP-2 expression in tumor metastases than in the primary tumor (72.7% versus 60.6%; p <0.01). The expressions of MMP-2 and EMMPRIN were highly correlated (rs = 0.466; p <0.01). CONCLUSIONS: Nasopharyngeal carcinoma cells may attain enhanced metastastic capability through the expression of MMP-2 induced by EMMPRIN.

Ferroptosis Regulator Modification Patterns and Tumor Microenvironment Immune Infiltration Characterization in Hepatocellular Carcinoma.

Accumulating studies have highlighted the biologic significances of ferroptosis modification in tumor progression, but little is known whether ferroptosis modification patterns have potential roles in tumor microenvironment (TME) immune cell infiltration of hepatocellular carcinoma (HCC). In this study, we evaluated 51 ferroptosis regulators and performed consensus clustering algorithm to determine ferroptosis modification patterns and the ferroptosis related gene signature in HCC. Gene set variation analysis (GSVA) was employed to explore biological molecular variations in distinct ferroptosis modification patterns. Single sample gene set enrichment analysis (ssGSEA) algorithm was performed to quantify the relative infiltration levels of various immune cell subsets. Principal component analysis (PCA) algorithm was used to construct the ferroptosisSig score to quantify ferroptosis modification patterns of individual tumors with immune responses. Three distinct ferroptosis modification patterns were identified. GSVA enrichment analysis indicated that three ferroptosis modification subgroups were enriched in different metabolic pathways. ssGSEA analysis determined that 19 of 24 immune infiltrating cells had significant differences in three distinct ferroptosis patterns. A 91-ferroptosis gene signature was constructed to stratify patients into two ferroptosisSig score groups. Patients in the higher ferroptosisSig score were characterized by significantly prolonged survival time compared with patients in the lower ferroptosisSig score group (p < .0001). An immunotherapy cohort confirmed patients with higher ferroptosisSig score determined significant therapeutic advantages and clinical benefits. Receiver operating characteristic (ROC) curve analysis confirmed the predictive capacity of anti-PD/L1 immunotherapy by ferroptosisSig score. Our study indicated the ferroptosis modification played a significant role in TME heterogeneity and complexity. Evaluating the ferroptosis modification pattern of individual tumor could strengthen our cognition of TME infiltration characteristics and guide more effective clinic immunotherapy strategies.

Prognostic significance of MRI-based late-course tumor volume in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: To validate tumor volume-based imaging markers for predicting local recurrence-free survival (LRFS) in locoregionally advanced nasopharyngeal carcinoma patients, who underwent induction chemotherapy followed by definitive intensity-modulated radiotherapy. METHODS: We enrolled 145 patients with stage III-IVA nasopharyngeal carcinoma in this retrospective study. Pre-treatment tumor volume (Vpre) and late-course volume (LCV) were measured based on the MRIs scanned before treatment and during the first 3 days in the sixth week of radiotherapy, respectively. The volume regression rate (VRR) was calculated according to Vpre and LCV. Receiver operating characteristic (ROC) curves were used to identify the cut-off best separating patient subgroups in assessing the prognostic value of Vpre, LCV and VRR. The Kaplan-Meier method was used for survival analysis. Prognostic analyses were performed using univariate and multivariate COX proportional hazard models. RESULTS: The LCV was 5.3 ± 0.5 (range 0-42.1) cm3; The VRR was 60.4 ± 2.2% (range 2.9-100.0). The median follow-up period was 36 months (range 6-98 months). The cut-off value of LCV determined by the ROC was 6.8 cm3 for LRFS prediction (sensitivity 68.8%; specificity 79.8%). The combination of LCV and VRR for LRFS prediction (AUC = 0.79, P < 0.001, 95% CI 0.67-0.90), LCV (AUC = 0.74, P = 0.002, 95% CI 0.60-0.88) and Vpre (AUC = 0.71, P = 0.007, 95% CI 0.56-0.85) are better than T category (AUC = 0.64, P = 0.062, 95% CI 0.50-0.79) alone. Patients with LCV ≤ 6.8 cm3 had significantly longer LRFS (P < 0.001), disease-free survival (DFS, P < 0.001) and overall survival (OS, P = 0.005) than those with LCV > 6.8 cm3. Multivariate Cox regression showed LCV was the only independent prognostic factor for local control (HR = 7.80, 95% CI 2.69-22.6, P < 0.001). CONCLUSIONS: LCV is a promising prognostic factor for local control and chemoradiosensitivity in patients with locoregionally advanced NPC. The LCV, and the combination of LCV with VRR are more robust predictors for patient survival than T category.

Comparing Long-Term Survival and Late Toxicities of Different Sequential Chemotherapy Regimens with Intensity-Modulated Radiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma.

OBJECTIVES: To evaluate long-term survival outcomes and late toxicities of the sequential chemotherapy regimen of gemcitabine plus cisplatin (GP) compared with cisplatin plus fluorouracil (PF) in locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From June 2005 to December 2014, 235 patients with pathologically confirmed NPC treated with intensity-modulated radiotherapy (IMRT) combined with GP (n = 144) or PF (n = 91) were retrospectively analyzed. RESULTS: After a median follow-up of 61 months, the 5-year overall survival (OS) rates were not significantly different between GP and PF groups (84.2% vs. 74.4%, P = .208). The 5-year local control rates were significantly improved in the GP group (96.3% vs 84.1%, P = .010). Subgroup analysis demonstrated that the increased benefits of GP were from T1-3 classification (99% vs. 87.8%, P = .013) and stage III patients (100% vs. 82.4%, P = .017). The most common late adverse events were xerostomia and hearing impairment. The incidences of grade 3 to 4 late toxicities were relatively low and were similar in the two groups. CONCLUSIONS: Sequential chemotherapy combined with IMRT achieved satisfactory survival outcomes in locoregionally advanced NPC with acceptable late toxicities. The GP regimen significantly improved local control compared with PF regimen. Further phase III randomized clinical studies were warranted.

Determination of nanograms of proteins based on decreased resonance light scattering of zwitterionic gemini surfactant.

A new high-sensitivity detection of protein assay at the nanogram level is proposed based on the decreased resonance light scattering (RLS) signals of zwitterionic gemini surfactant (phosphodiesters quaternary ammonium salt [PQAS]). It was found that PQAS self-assembled into nanometer-scale PQAS aggregates, which induced intense RLS signal in Britton-Robinson (BR) buffer solution (pH 10.5). Under the optimum conditions, the RLS intensity quenching extent of PQAS aggregation was in proportion to the concentration of proteins in the range of 0.0012-1.08 microg/ml for bovine serum albumin, 0.0015-0.95 microg/ml for human serum albumin, and 0.0025-1.3 microg/ml for gamma-globulin. The detection limits were 0.8, 1.2, and 2.0 ng/ml, respectively. The proposed method was successfully applied to determine total protein in human serum samples, and the results were identical to those obtained by the Bradford assay. The mechanism of interaction between PQAS and protein was studied using RLS, fluorescence, and time-resolved fluorescence, which indicated that the new complex formed between them, disaggregating self-aggregation of PQAS, resulted in the dominated quenching of RLS signal of the assay system.

Intensity-modulated radiotherapy combined with sequential cisplatin and fluorouracil chemotherapy for locoregionally advanced nasopharyngeal carcinoma.

To investigate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) combined with induction-adjuvant cisplatin and fluorouracil (PF) in locoregionally advanced nasopharyngeal carcinoma (NPC).A total of 91 biopsy-proven NPC patients treated with IMRT were retrospectively analyzed. All patients received induction chemotherapy (IC) consisting of cisplatin 25 mg/m2 on day 1 to 3, and 5-Fu 2500 mg/m as an intravenous infusion over 120 hours every 3 weeks for 2 cycles. Adjuvant chemotherapy of the same regime was given 28 days after the end of IMRT.A total of 87 patients completed 2 cycles of IC. During adjuvant chemotherapy phase, 74.7% patients received at least 1 cycle. With a median follow-up time of 45 months (10-123 months), the 5-year local control, regional control, distant metastasis-free (DMF) and overall survival (OS) rates were 84.1%, 86.9%, 81.3%, and 74.4%, respectively. The 5-year local control rates for patients with Stage T1-2 and T3-4 was 94.6% and 76.5%, respectively (P = .045). The 5-year DMF rates for patients with N0-1 and N2-3 diseases were 90.6% and 73.3%, respectively (P = .072). During radiotherapy (RT), 24.2% patients suffered severe acute mucositis (grade 3-4). Severe late toxicities included cranial nerve palsy in 1 patient and grade 3 hearing impairment in 1 patient.IMRT combined with induction-adjuvant chemotherapy consisting of PF regimen is well tolerated and provides satisfactory local-regional control for locoregionally advanced NPC. Further treatment strategies to control distant metastasis are needed in the future.

Corrigendum to "Long-term results of a phase II study of gemcitabine and cisplatin chemotherapy combined with intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma" [Oral Oncol. 73 (2017) 118-123].

OBJECTIVES: To evaluate long-term results of a phase II study of induction and adjuvant gemcitabine and cisplatin (GP) chemotherapy with intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: One hundred and twelve patients (Stage III: 65, IVA-B: 47) with locoregionally advanced NPC were enrolled in this study. All patients received induction chemotherapy consisting of 1000 mg/m2 gemcitabine on day 1 and 8, and cisplatin 25 mg/m2 on day 1-3, every 3 weeks for 2 cycles. Adjuvant chemotherapy for 2 cycles of the same regime was given 28 days after the end of IMRT. The IMRT technique was utilized for all patients. RESULTS: In total, 97.3% patients completed 2 cycles of induction chemotherapy. The overall response rate (RR) of cervical lymph nodes was 89.0%. Acute toxicities were mainly grade 1-2 myleosuppression and vomiting. And 83.9% patients completed 2 cycles of adjuvant chemotherapy. All patients finished IMRT with RR at the end of IMRT for nasopharynx, lymph nodes of neck and retropharyngeal area being 99.1%, 97.9% and 97.7%, respectively. The 5-year local control, regional control, distant metastasis-free and overall survival rates were 93.2%, 92.3%, 89.0% and 82.1%, respectively. The 5-year overall survival of stage III and IVA-B were 87.0%, and 75.5%, respectively. The incidence of grade 3-4 acute radiotherapy-related mucositis was 28.6%. Severe late toxicities were uncommon. CONCLUSION: IMRT combined with GP for locoregionally advanced NPC is well tolerated, effective, and convenient, and warrants further studies.

Long-term results of a phase II study of gemcitabine and cisplatin chemotherapy combined with intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma.

Objectives: To evaluate long-term results of a phase II study of induction and adjuvant gemcitabine and cisplatin (GP) chemotherapy with intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). Materials and methods: One hundred and twelve patients (Stage III: 65, IVA-B: 47) with locoregionally advanced NPC were enrolled in this study. All patients received induction chemotherapy consisting of 1000 mg/m2 gemcitabine on day 1 and 8, and cisplatin 25 mg/m2 on day 1­3, every 3 weeks for 2 cycles. Adjuvant chemotherapy for 2 cycles of the same regime was given 28 days after the end of IMRT. The IMRT technique was utilized for all patients. Results: In total, 97.3% patients completed 2 cycles of induction chemotherapy. The overall response rate (RR) of cervical lymph nodes was 89.0%. Acute toxicities were mainly grade 1­2 myleosuppression and vomiting. And 83.9% patients completed 2 cycles of adjuvant chemotherapy. All patients finished IMRT with RR at the end of IMRT for nasopharynx, lymph nodes of neck and retropharyngeal area being 99.1%, 97.9% and 97.7%, respectively. The 5-year local control, regional control, distant metastasis-free and overall survival rates were 93.2%, 92.3%, 89.0% and 82.1%, respectively. The 5-year overall survival of stage III and IVA-B were 87.0%, and 75.5%, respectively. The incidence of grade 3­4 acute radiotherapy-related mucositis was 28.6%. Severe late toxicities were uncommon. Conclusion: IMRT combined with GP for locoregionally advanced NPC is well tolerated, effective, and convenient, and warrants further studies.

Downregulation of Epstein-Barr virus-encoded latent membrane protein-1 by arsenic trioxide in nasopharyngeal carcinoma cells.

AIMS AND BACKGROUND: It was documented that nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) and that EBV-encoded latent membrane protein-1 expression (LMP1) plays an important role in the pathogenesis of NPC. In preclinical studies, arsenic trioxide (As2O3) has been identified as a promising anticancer agent for treatment of NPC. The purpose of this study is to investigate if this agent can inhibit the expression of LMP1 and therefore lead to growth inhibition of NPC cells in vitro. METHODS: LMP1-positive NPC cells, HNE1-LMP1, were treated with 3 micromol/L of As2O3 for 96 hours. The LMP1 protein expression and mRNA level in HNE1-LMP1 cells were determined by western blot, confocal immunofluorescence staining and semiquantitative reverse transcriptase reaction (RT-PCR). Apoptosis was determined by light microscopy and the TUNEL method. Alterations in the cell cycle distribution were also investigated by flow cytometry. MTT assay and colony formation assay were used to detect the proliferation of the cells. The LMP1-negative parental cell lines HNE1 and HNE2 were used as control in an attempt to elucidate the role of LMP1 in the anticancer effect of As2O3 on NPC cells. RESULTS: The expression of LMP1 at the protein and mRNA level was reduced after exposure to 3 micromol/L As2O3. This dose of As2O3 significantly induced apoptosis and growth retardation of HNE1-LMP1 cells. In addition, more HNE1-LMP1 cells were induced to G0/G1 and G2/M arrest. The same dose of As2O3 had a moderate effect on HNE1 and HNE2 cells. CONCLUSION: Arsenic trioxide can inhibit LMP1 expression and dictate apoptosis and alterations of cell cycle distribution as well as growth retardation. LMP1-positive NPC cells are more sensitive to As2O3 treatment than LMP1-negative NPC cells.

[Expression and significance of heat shock proteins in esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the expression and significance of HSP27, HSP60, HSP70 and HSP90 alpha in esophageal squamous cell carcinoma (ESCC) and tissues along the incision margin (TIM). METHODS: The presence and the level of expression of HSP27, HSP60, HSP70 and HSP90 alpha were determined in 168 specimens from ESCC and 42 from tissues along TIM by EnVision immunohistochemistry and Western blotting, to compare their positive staining rates and explore the correlation between their expressions and clinicopathologic features in ESCC. RESULTS: The positive staining rates of HSP27, HSP60, HSP70 and HSP90 alpha in ESCC and TIM were 62.0% and 42.1%, 92.7% and 63.2%, 57.9% and 22.2%, and 33.7% and 18.5%, respectively. There was very significant difference between the expression of HSP60 and HSP70 in ESCC and TIM (P < 0.01), but not significant about HSP27 and HSP90 alpha (P > 0.05). The positive staining rate of HSP27 declined with the lower grade of differentiation of ESCC (P < 0.05). CONCLUSION: The present findings suggest that the expression of HSPs of different molecular weight in ESCC and TIM is a common event. The level of expressions of HSP60 and HSP70 are higher than those in TIM. HSP60 and HSP70 expression correlated with the biological behavior of ESCC. The expression of HSP27 was positively correlated to the grade of differentiation of ESCC. Overexpression of HSP27 may be associated to the differentiation of squamous cell carcinoma.

Tumor Regression and Patterns of Distant Metastasis of T1-T2 Nasopharyngeal Carcinoma with Intensity-Modulated Radiotherapy.

PURPOSE: To study tumor regression and failure patterns in T1-T2 non-metastatic nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). METHODS: A retrospective analysis of 139 nasopharyngeal carcinoma patients treated with IMRT between January 2005 and December 2010 in our center was performed. According to the AJCC staging system, all primary lesions were attributed to T1 and T2. The prescription doses were 66 Gy at 30 fractions to gross tumor volume of the nasopharynx and the positive neck nodes, 60 Gy to high-risk clinical target volume and 54 Gy to low-risk clinical target volume. Patients staged III, IV A/B or II (lymph node measured 4 cm or more in diameter) received platinum-based chemotherapy. RESULTS: By the end of radiotherapy, 7.2% (10/139), 23.7% (33/139), and 9.4% (13/139) of patients had residual lesions in the nasopharynx, cervical lymph nodes and retropharyngeal lymph nodes, respectively. The majority of patients had complete remission within 6 months of radiotherapy completion. Five months after IMRT, three patients with residual tumors in the cervical lymph nodes underwent surgery. Among these patients, two patients had positive pathological findings, and one patient had negative findings. With a median follow-up of 59 months, the 5-year overall survival, local control, regional control and distant metastasis-free rates were 87.8%, 96.7%, 94.9% and 89.1%, respectively. Fifteen patients developed distant metastases, representing the primary failure pattern. CONCLUSIONS: Most residual lesions that persisted after IMRT vanished completely in six months. Considering the potential damage to normal structures, clinicians should be cautious when considering the use of boost irradiation after radiotherapy. Distant metastasis was the primary cause of treatment failure, which was significantly higher in N2-3 patients than in N0-1. Additional studies to better understand distant metastases are needed.

Loss of CADM1/TSLC1 Expression Is Associated with Poor Clinical Outcome in Patients with Esophageal Squamous Cell Carcinoma.

Aims. We sought to determine the relationship between CADM1/TSLC1 expression and clinicopathological characteristics in patients with esophageal squamous cell carcinoma (ESCC) and the correlation with survival. Materials and Methods. Two hundred and ninety-three ESCC tissues and paired adjacent normal esophageal tissues were immunohistochemically assessed in this study. The association of CADM1/TSLC1 with clinicopathological parameters, as well as disease-free survival (DFS) and overall survival (OS), was determined based on the Kaplan-Meier method and Cox regression models. Results. CADM1/TSLC1 was detected in 236 (80.5%) tumor tissues and 19 (8.0%) paired adjacent normal esophageal tissues. Decreased CADM1/TSLC1 expression was correlated with more advanced histological grade. CADM1/TSLC1 negative tumors were more frequently observed in male cases than in female cases. DFS and OS in the CADM1/TSLC1 negative group were significantly shorter than those in the positive group, particularly in male patients with ESCC. Conclusion. Loss or reduction of CADM1/TSLC1 expression is associated with more advanced histological grade and predicts early recurrence and short survival duration. Thus, loss of CADM1/TSLC1 could be a prognostic factor that can be used to assess the risk of recurrence and survival.

Asymmetric Collagen/chitosan Membrane Containing Minocycline-loaded Chitosan Nanoparticles for Guided Bone Regeneration.

Infections caused by pathogens colonization at wound sites in the process of bone healing are considered as one of the major reasons for the failure of guided bone regeneration (GBR). The objective of this study was to prepare a novel asymmetric collagen/chitosan GBR membrane containing minocycline-loaded chitosan nanoparticles. The morphologies of the membranes and nanoparticles were observed by SEM and TEM, respectively. The characterization and biocompatibility of the membranes was evaluated. The effect of the membrane on bone regeneration was assessed using the critical-size at cranial defect model. TEM images showed the spherical morphology of the nanoparticles. The results of SEM indicated that the asymmetric membrane contained a dense collagen layer and a loose chitosan layer. An in vitro experiment showed that the membrane can inhibit bacterial growth and promote osteoblasts and fibroblasts growth. The membrane showed the ability to promote angiogenesis and enhance bone regeneration in vivo. An asymmetric collagen/chitosan GBR membrane can be fabricated by loading minocycline encapsulated chitosan nanoparticles, and shows satisfactory biocompatibility and barrier function, which enhances bone regeneration. Therefore, this antibacterial GBR membrane is a promising therapeutic approach to prevent infection and guide bone regeneration.