Recombined humanized endostatin (Endostar) intravenous infusion in the treatment of refractory nasopharyngeal carcinoma: Three case reports.

RATIONALE: Refractory nasopharyngeal carcinoma is challenging to treat and at present there is no standard treatment or any good choice. PATIENT CONCERNS: Although the three patients in our case reports had already underwent multiple treatments before, they still suffered from disease recurrence of nasopharyngeal carcinoma. DIAGNOSIS: They were diagnosed as refractory nasopharyngeal carcinoma. INTERVENTIONS: A continuous infusion of Endostar, an antiangiogenic agent, combined with chemotherapy and radiation therapy was given to treat the patients. OUTCOMES: Patients showed complete or partial response to the combined therapy as evidenced by regression of tumors and decrease in plasma Epstein-Barr virus (EBV) DNA load. LESSONS: Continuous infusions of Endostar in combination with chemotherapy and/or radiation therapy showed promising efficacy and safety. The combination therapy indicates a new approach to treat refractory nasopharyngeal carcinoma.

[Prokaryotic Expression and Purification of the Notch Ligand and Its Effect on Hematopoiesis after Carbon Tetrachloride Damage].

OBJECTIVE: To express and purify the mouse endothelial cell-targeted recombinant Notch ligand protein mD1R, and to investigate its effect on hematopoiesis after carbon tetrachloride damage. METHODS: PCR was performed to clone and construct the expression vector pET22b(+)-mD1R. The mD1R successfully transformed into E. coli was induced by IPTG, and purified with Ni2+-beads affinity chromatography. The target protein was detected by SDS-PAGE. The fluorescence-activated cell sorting analysis (FACS), cell adhesion test, immunofluorescence staining and quantitative real-time PCR were employed to detect the endothelial cell-targeted and Notch signaling-activated biological characteristics of mD1R. The carbon tetrachloride mouse model was established to observe the effects of mD1R on the hematopoietic stem cell (HSC), myeloid cells and lymphoid cells by flow cytometry. The Lin-Scal-1+c-Kit+ cells were sorted by magnetic bead, FACS was performed to analyze the cell cycle, and RT-PCR was employed to observe the expression of interleukin (IL)-10. RESULTS: The prokaryotic expression vector was successfully cloned and constructed. The purity and the activity were confirmed in mD1R recombinant protein. The purified mD1R activated the Notch signaling pathway of hematopoietic stem cells in carbon tetrachloride damaged mouse, and internally elevated the number of HSC and long-term HSC to 2.96-fold and 6.18-fold. In addition, mD1R improved the amplification of the myeloid progenitor cells and the myeloid-derived suppressor cells, particularly the granulocyte/monocyte into blood. Mechanistically, the further analyses suggested that Notch pathway could increase the proliferation of HSC and enhance expression of IL-10 after stress injury. CONCLUSIONS: A new and activated recombinant Notch ligand protein has been obtained successfully to communicate hematopoietic stem cells and hematopoietic microenvironment. The Notch- mediated intrinsic hematopoiesis has been regulated by the anti-inflammatory factor after stress injury.

An inflammatory biomarker-based nomogram to predict prognosis of patients with nasopharyngeal carcinoma: an analysis of a prospective study.

Chronic inflammation plays an important role in tumor progression. The aim of this analysis was to evaluate whether inflammatory biomarkers such as the Glasgow prognostic score (GPS), the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the lymphocyte-monocyte ratio (LMR) could predict the prognosis of nasopharyngeal carcinoma (NPC). In this analysis, pretreatment GPS, NLR, PLR, LMR of 388 patients who were diagnosed as nonmetastatic NPC and recruited prospectively in the 863 Program No. 2006AA02Z4B4 were assessed. Of those, the 249 cases enrolled between December 27th 2006 and July 31st 2011 were defined as the development set. The rest 139 cases enrolled between August 1st 2011 and July 31st 2013 were defined as the validation set. The variables above were analyzed in the development set, together with age, gender, Karnofsky performance score, T stage, and N stage, with respect to their impact on the disease-specific survival (DSS) through a univariate analysis. The candidate prognostic factors then underwent a multivariate analysis. A nomogram was established to predict the DSS, by involving the independent prognostic factors. Its predction capacity was evaluated through calculating Harrell's concordance index (C-index) in the validation set. After multivariate analysis for the development set, age (≤50 vs. >50 years old), T stage (T1-2 vs. T3-4), N stage (N0-1 vs. N2-3) and pretreatment GPS (0 vs. 1-2), NLR (≤2.5 vs. >2.5), LMR (≤2.35 vs. >2.35) were independent prognostic factors of DSS (P values were 0.002, 0.008, <0.001, 0.004, 0.018, and 0.004, respectively). A nomogram was established by involving all the factors above. Its C-index for predicting the DSS of the validation set was 0.734 (standard error 0.056). Pretreatment GPS, NLR, and LMR were independent prognostic factors of NPC. The nomogram based on them could be used to predict the DSS of NPC patients.

[The biological behavior of hepatocarcinoma stem cells in rats].

OBJECTIVES: To study the biological behavior of hepatocarcinoma stem cells in rats. METHODS: Primary liver carcinomas were induced in rats using diethylnitrosamine. Tumor cells from 8 rats were separated according to rats oval cell (OVC) markers CD34, c-Kit, Thy-1, AFP, CK7, CK8, CK14, CK18, CK19 and GGT and then they were separately injected into the livers of nude mice. The tumors grown from the different subpopulation of OVC markers in the nude mice livers (10 OVC markers negative or positive cells) were weighted 1 month after the inoculations. The hepatocarcinoma cell subpopulations with higher ability in causing tumor growths were further studied in vitro. The cell cycles and DNA content of those subpopulation cells were investigated using flow cytometry. RESULTS: (1) Subpopulation cells with CK7(-), Thy-1(+) and AFP(+) markers had a higher ability in causing tumors in nude mice; (2) Subpopulation cells, exhibiting characters of TSC, had a low growth rate in vitro. CONCLUSIONS: (1) Different subpopulations of hepatocarcinoma cells had different abilities in causing tumors in rats. Some subpopulation cells, such as CK7(-), Thy-1(+) and AFP(+) cells, have characteristics of tumor stem cells. (2) The hepatocarcinoma stem cells may have a low growth rate in vitro.

[Effects of basic fibroblast growth factor on rat models of Alzheimer disease].

OBJECTIVE: To study the effects of basic fibroblast growth factor (bFGF) on the praxiology and cerebral acetylcholinesterase (AchE) fiber density of kainic acid-lesioned rat models of Alzheimer disease (AD). METHODS: AD models were induced in 30 normal adult rats by damaging the rat nucleus basalis of Meynert (NBM) with kainic acid, and the models were then assigned into 3 groups to receive cerebroventricular infusion with bFGF, saline or nothing for treatment, serving respectively as the treatment group at 30 min, 1, 3 and 7 d after the injury, sham treatment group or injury group. Another 10 rats were used as control group, which received saline injections into the NBM without further treatment. The learning and memory abilities of the rats were measured through Y-maze test 30 d after the operations, and AchE cytochemical study was conducted to calculate the density of the AchE fibers in the hippocampus and forebrain of the rats. RESULTS: In comparison with the injury group, improvement was noted in the memory ability of rats with bFGF treatment and the density of AchE fiber was also significantly increased (P<0.01), but the improvement in both respects failed to reach the normal level (P<0.01). CONCLUSIONS: AD model can be successfully established by damaging the NBM with kainic acid, and bFGF is beneficial in improving the impaired learning and memory abilities and increasing the density of AchE fibers in the basal forebrain cortex and hippocampus in the models.

[Expression of serum sICAM-1 in patients with primary hepatocellular carcinoma and its relationship with liver fibrosis].

AIM: To explore the clinical value of serum soluble intercellular adhesion molecule-1 (sICAM-1) in patients with primary hepatocellular carcinoma (PHC) and its relationship with liver fibrosis. METHODS: The serun sICAM-1, PC III, IV-C, LN and HA level of 45 cases of patients with PHC, 30 cases of benign tumor and 35 cases of healthy people were determined by ELISA, the relationship between sICAM-1 and liver fibrosis was analyzed. RESULTS: The serum sICAM-1, PC III, IV-C, LN and HA levels of the PHC group were significantly higher than that of the benign tumor group and normal control group, compared the difference was significant (P<0.05); The serum markers was no significant difference between the benign tumor group and normal control group (P>0.05); The serum sICAM-1 was positively correlated with the PC III, IV-C, LN and HA (γ= 0.683, 0.575, 0.573 and 0.539, P<0.05). CONCLUSION: Detection of serum sICAM-1 has important clinical significance for assessing the PHC patient's condition, early diagnosing and treating liver cancer.

[Correlation of antitumor drug sensitivity between marrow mesenchymal stem cells (MSCs) and hepatocarcinoma cells in rats].

BACKGROUND & OBJECTIVE: As hepatocarcinoma stem cells may originate from oval cells and oval cells are difficult to be separated and purified, MSCs (marrow mesenchymal stem cells), which are the progenitor cells of the hepatocarcinoma stem cells, were selected instead in our study to investigate the correlation of anticancer drug sensitivity between hepatocarcinoma cells and MSCs in rats. METHODS: The primary liver carcinoma modle of rats was induced by diethylnitrosamine. Tumor cells and MSCs from eight hepatocarcinoma rats were separated. The inhibitory effects of 3 anticancer drugs [adriacin (0.04 microg/ml), cisplatin (0.2 microg/ml) and fluorouracil (1 microg/ml)] to hepatocarcinoma cells and MSCs were measured by MTT assay. The weight of the tumor in nude mice which were injected with rat hepatocarcinoma cells was measured after 6 weeks. Then the correlation of the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and MSCs, and to the tumor weight of nude mice was analyzed. RESULTS: No correlation was revealed between the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and the tumor weights of nude mice injectal with drug treated tumor cells. The correlation coefficient was: 0.6307 (adriacin, P>0.05), 0.4358 (fuiorouracil, P>0.05) and 0.7080 (cisplatin, P>0.05). No correlation was observed between the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and to MSCs. The correlation coefficient was: 0.6316 (adriacin, P>0.05), 0.4214 (fluorouracil, P>0.05) and 0.5943 (cisplatin, P>0.05). However, significant reverse correlation was found between the inhibitory ratio of 3 anticancer drugs to MSCs and the tumor weights of nude mice injectal with drug treated tumor cells. The correlation coefficient was: -0.8308 (adriacin, P<0.05), -0.8991 (fluorouracil, P<0.01) and -0.8311 (cisplatin, P<0.05). CONCLUSIONS: Conventional anticancer drug sensitivity experiments could not reflect the chemoresistance of the hepatocarcinoma cells. However the inhibitory ratio of the anticancer drugs to MSCs in the hepatocarcinoma rats can reflect the chemoresistance of hepatocarcinoma cells accordingly.