Anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To identify anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma (M1-NPC). MATERIALS AND METHODS: All M1-NPC treated with chemotherapy and/or radiotherapy between 2010 and 2019 from two centers (training and validation cohort) were included. The prognostic value of metastatic disease extent and involved organs for overall survival (OS) were assessed by several multivariable analyses (MVA) models. A new M1 classification was proposed and validated in a separate cohort who received immuno-chemotherapy. RESULTS: A total of 197 M1-NPC in the training and 307 in the validation cohorts were included for M1 subdivision study with median follow-up of 46 and 57 months. MVA model with "≤2 organs/≤5 lesions" as the definition of oligometastasis had the highest C-index (0.623) versus others (0.606-0.621). Patients with oligometastasis had better OS versus polymetastasis (hazard ratio [HR] 0.47/0.63) while liver metastases carried worse OS (HR 1.57/1.45) in MVA in the training/validation cohorts, respectively. We proposed to divide M1-NPC into M1a (oligometastasis without liver metastases) and M1b (liver metastases or polymetastasis) with 3-year OS of 66.5%/31.7% and 64.9%/35.0% in the training/validation cohorts, respectively. M1a subset had a better median progress-free survival (not reach vs. 17 months, p < 0.001) in the immuno-chemotherapy cohort (n = 163). CONCLUSION: Oligometastasis (≤2 organs/≤5 lesions) and liver metastasis are prognostic for M1-NPC. Subdivision of M1-NPC into M1a (oligometastasis without liver metastasis) and M1b (liver metastasis or polymetastasis) depicts the prognosis well in M1-NPC patients who received immuno-chemotherapy.

Comparison of radiotherapy combined with nimotuzumab vs. chemoradiotherapy for locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). METHODS: Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. RESULTS: A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). CONCLUSION: Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

The Vascular Notch Ligands Delta-Like Ligand 4 (DLL4) and Jagged1 (JAG1) Have Opposing Correlations with Microvascularization but a Uniform Prognostic Effect in Primary Glioblastoma: A Preliminary Study.

PURPOSE: Delta-like ligand 4 (DLL4) and Jagged1 (JAG1), 2 vascular Notch ligands, are involved in the process of tumor angiogenesis. The present study investigates their relationship with microvascularization and the prognostic effect in primary glioblastoma. METHODS: Tumor tissues from 61 glioblastomas were analyzed using immunohistochemistry for DLL4/JAG1 expression and microvascular formations. The correlations between DLL4/JAG1 and microvascularization were analyzed. The survival probabilities were computed using the Kaplan-Meier method. The Cox proportional hazards regression model was used for multivariate analysis of time to progression (TTP) and overall survival (OS). RESULTS: The results showed increased DLL4 and JAG1 expression in glioblastoma tissues. Five types of basic microvascular formations, including microvascular sprouting, vascular cluster, vascular garland, glomeruloid vascular proliferation, and vasculogenic mimicry, were detected. Glioblastomas with the type I microvascular pattern (MVP) that displayed prominent microvascular sprouting and vascular clusters tended to have higher DLL4 expression, whereas those with the type II MVP that had numerous vascular garlands, glomeruloid vascular proliferations, and vasculogenic mimicries showed upregulated JAG1 expression. Univariate analysis documented that high DLL4 expression, high JAG1 expression, and type II (MVP) were statistically associated with reduced TTP and OS. Multivariate analysis confirmed high DLL4 expression, high JAG1 expression, and type II MVP as significant prognostic factors for both shorter TTP and OS, independent of age, Karnofsky performance scale, and other molecular markers (vascular endothelial growth factor, Ki67, and P53). CONCLUSIONS: DLL4 and JAG1 may have opposing effects on tumor angiogenesis in glioblastoma. The Notch pathway may be a new target for antiangiogenic therapy in glioblastoma.

High Jagged1 expression is associated with poor outcome in primary glioblastoma.

Glioblastoma is a highly aggressive brain tumor. Aberrant Notch pathway has been implicated in the formation and progression of glioblastoma. The present study attempted to investigate the expression of Notch ligand Jagged1 and its association with patient outcome in primary glioblastoma. Tumor tissues from 82 patients with primary glioblastoma were analyzed using immunohistochemistry for Jagged1 expression. Relationships between Jagged1 expression and clinical features (age, gender, KPS, symptom duration, extent of resection and Ki67 index) were evaluated. The prognostic value of Jagged1 was assessed using the Kaplan-Meier survival estimates and the Cox proportional hazard models. Immunohistochemistry results showed markedly increased Jagged1 expression in glioblastoma tissues compared to adjacent non-neoplastic brain tissues. Univariate analysis documented that high Jagged1 expression in tumor cells (TC) and endothelial cells (EC) were both statistically associated with reduced time to progression (TTP) (P < 0.001 for TC, P = 0.001 for EC) and overall survival (OS) (P < 0.001 for TC, P = 0.003 for EC) in primary glioblastoma. The median TTP (P < 0.001) and OS (P = 0.001) were higher in patients with dual-low Jagged1 expression in TC and EC compared to those in patients with non-dual Jagged1 expression and dual high expression. By multivariate survival analysis, we found that high Jagged1 expression in both tumor cells and endothelial cells was independent unfavorable prognostic factors TTP (P < 0.001 for TC, P < 0.001 for TC) and OS (P < 0.001 for TC, P < 0.001 for TC) in primary glioblastoma patients. Jagged1-Notch signaling plays an important role in the progress of glioblastoma. Jagged1 expression may be used as an independent prognosis factor in patients with glioblastoma.

[Petroleum hydrocarbon pollution status in shellfish culture area of Sanggou Bay and effect on quality safety of shellfish].

Petroleum hydrocarbon concentrations in seawater, surface sediments and culture shellfish were investigated in shellfish culture area of Sanggou Bay from Jan. to Nov. in 2008. Investigation was conducted on the distribution and variation of petroleum hydrocarbon concentrations in seawater and sediments in the shellfish culture area of Sanggou Bay, as well as on the levels and the differences in petroleum hydrocarbon concentrations among the shellfish species. In addition, the petroleum hydrocarbon pollution status in the three media was evaluated and the effects of accumulated petroleum hydrocarbon in shellfish on the food safety risk were discussed. The results indicated: 1) Petroleum hydrocarbon concentrations in seawater in the shellfish culture area of Sanggou Bay were in the range of 3.61 - 98.21 microg/L; the mean values of petroleum hydrocarbon concentrations in sediments were in the range of 6.75-25.95 mg/kg; petroleum hydrocarbon concentrations in culture shellfish were in the range of 2.14- 42.87 mg/kg; and petroleum hydrocarbon concentrations in shellfish varied largely among different species, with the mean values in the sequence of clam Venerupis variegata > oyster > scallop; 2) Monthly petroleum hydrocarbon concentrations in seawater and surface sediments varied significantly in Sanggou Bay shellfish culture area, with the highest and the lowest values of petroleum hydrocarbon concentrations in seawater that occurred in July and in August, respectively, and with the highest and the lowest values of petroleum hydrocarbon concentrations in surface sediments that occurred in September and in March, respectively; 3) According to the corresponding evaluation criteria, the petroleum hydrocarbon pollution status in surface sediments in Sanggou Bay shellfish culture area was unpolluted but the status in surface seawater was polluted. The culture shellfish was also polluted by petroleum hydrocarbon with different degrees among three species, namely, the pollution degree of clam Venerupis variegata and oyster was more serious than that of scallop Chlamys farreri; 4) The results of linear regression analysis showed that petroleum hydrocarbon concentrations in shellfish had a significantly positive correlation with the concentrations in seawater, while the linear correlation between the concentrations in shellfish and surface sediments was not obvious; and 5) According to the pollution level of petroleum hydrocarbon in shellfish, the food safety risk of three culture shellfishes in Sanggou Bay was relatively low.

[Distribution of organic carbon and carbon fixed strength of phytoplankton in Enteromorpha prolifera outbreak area of the Western South Yellow Sea, 2008].

Based on the analysis of dissolved organic carbon (DOC), particulate organic carbon (POC) and particulate nitrogen (PN) of the samples collected from stations in Enteromorpha prolifera outbreak area of the Western South Yellow Sea during the period August 9-13 of 2008, combining with the data of environmental hydrology, the horizontal distribution, source and influential factors of organic carbon and carbon fixed strength of phytoplankton were discussed. The results showed that the concentrations of DOC and POC ranged from 1.55 mg/L to 3.22 mg/L, 0.11 mg/L to 0.68 mg/L, with average values of 2.44 mg/L and 0.27 mg/L. The horizontal distributions of DOC and POC were similar in study area. The concentrations of DOC and POC in coastal area were higher than that in the outer sea and the concentrations of DOC and POC at surface water layer were higher than those at the bottom water layer. There were a positive correlation between POC and TSS, indicating that the concentrations and source of TSS were main factors for the POC. According to the univariate linear regression model between POC and PN, the concentrations of particulate inorganic nitrogen (PIN) were evaluated. Removing the content of PIN in the samples, the average POC/PON values in most coastal waters were less than 8, combining with the values of POC/chlorophyll a, suggesting that the marine primary production were the important source of POC in most coastal waters, and the presence of degraded organic matter which derived from degraded Enteromorph prolifera was in the latter period of green tide outbreak. The results of evaluated carbon fixed strength based on primary productivity showed that carbon fixed strength of phytoplankton in Enteromorpha prolifera outbreak area of the Western South Yellow Sea ranged from 167 mg/(m2 x d) to 2017 mg/(m2 x d), with the average of 730 mg/(m2 x d). The daily carbon fixed quantities of the study area were up to 2.95 x 10(4) t. Then the daily carbon fixed quantities of the Yellow Sea were 28.03 x 10(4) t.

[Diffusive fluxes of dissolved inorganic nitrogen across sediment-water interface in net-cage culture area of Tangdao Bay].

Abstract: On basis of field data measured during 4 cruises from August 2004 to May 2005, concentrations of NH4+ -N, NO3- -N, NO2- -N in overlying and interstitial waters of sediments in net-cage culture areas of Tangdao Bay were analyzed. Moreover, diffusive fluxes of dissolved inorganic nitrogen from sediments were estimated by Fick's first law. Results showed that the main form of inorganic nitrogen in overlying and interstitial waters of sediments was NO3- -N, accounting for 73.34% and 61.45% respectively. Concentrations distributions of dissolved inorganic nitrogen (DIN) and NO3- -N in overlying water varied seasonally, which got their maximum concentration in October 2004 while the NH4+ -N concentration showed a little difference. The seasonal change of dissolved inorganic nitrogen (DIN) and NO3- -N, NH4+ -N in interstitial water varied similarly and also got their maximum concentration in October 2004. The concentration of NO2- -N in overlying and interstitial waters increased from spring to winter. The average fluxes of NH4+ -N, NO3- -N, NO2- -N were separately 5.46, -5.04, 8.71 micromol/(m2 x d). And NO2- -N was the most diffusive flux component in net-cage culture area of Tangdao Bay.