Radiotherapy vs sequential pegaspargase, gemcitabine, cisplatin and dexamethasone and radiotherapy in newly diagnosed early natural killer/T-cell lymphoma: A randomized, controlled, open-label, multicenter study.

To compare the efficacy and safety of radiotherapy (RT) and chemotherapy of pegaspargase, gemcitabine, cisplatin and dexamethasone (DDGP) combined with RT in newly diagnosed stage I-II natural killer/T-cell lymphoma (NKTL), we designed a randomized, controlled, open-label, multicenter clinical trial. Data from 65 stage I-II NKTL patients whose diagnoses were confirmed using immunohistochemistry were enrolled from January 2011 to December 2013 in the First Affiliated Hospital of Zhengzhou University. Patients were randomly divided into the RT group (n = 35) and the DDGP combined with RT group (n = 30). There was a difference between the Eastern Cooperative Oncology Group (ECOG) score in the two arms (P = .013). The complete response rate (CRR) and objective response rate (ORR) of DDGP combined with RT group were superior to those in the RT group (CRR: 73.3% vs 48.6%; ORR: 83.3% vs 60.0%, respectively). The 5-year progression-free survival (PFS) rate and overall survival (OS) rate in the DDGP combined with RT group were higher than those in the RT group (82.9% vs 56.5% for PFS, P = .023; 85.7% vs 60.4% for OS, P = .040), and treatment methods and lactate dehydrogenase were independent risk factors. Myelosuppression (P < .001), gastrointestinal reactions (P < .001), abnormal liver function (P = .007), coagulation abnormalities (P < .001) and baldness (P < .001) were more likely to occur in the DDGP combined with RT group. In conclusion, DDGP combined with radiotherapy obviously obtained great efficacy and prolonged the survival time of patients, also the side effects were mild for stage I-II NKTL. This trial was registered at https://register.clinicaltrials.gov as #NCT01501136.

Co-delivery of paclitaxel and gemcitabine by methoxy poly(ethylene glycol)-poly(lactide-coglycolide)-polypeptide nanoparticles for effective breast cancer therapy.

Traditional chemotherapeutic drugs have shown limited clinical curative effects in antitumor therapy. The application of multidrug combination and adjuvant-drug carriers is a feasible strategy to overcome the limitations while minimizing the dosage of single drug and acquiring the synergistic effects in tumor therapy. However, the systemic toxicity, drug resistance, and tumor recurrence are still unavoidable. Here we develop core-shell nanoparticles (NPs) to encapsulate paclitaxel (PTX) and gemcitabine (GEM) for breast cancer therapy. We find that the NPs could encapsulate PTX and GEM, with an encapsulation efficiency of 96.3 and 95.13%, respectively. Moreover, the drug loading of these NPs is 2.71% (PTX) and 2.64% (GEM). Notably, the co-delivery of GEM and PTX performs enhanced anticancer effect compared with the PTX alone or GEM alone therapy at the same concentration, which indicates a synergistic effect. Moreover, encapsulation of PTX and GEM by methoxy poly(ethylene glycol)-poly(lactide-coglycolide) also shows enhanced anticancer effects (81.5% tumor inhibition) and reduced systemic toxicity in vivo compared with free drugs (65% tumor inhibition). Together with those results, co-delivery of PTX and GEM by methoxy poly(ethylene glycol)-poly(lactide-coglycolide) might have important potencies in clinical applications for breast cancer therapy.

Effectiveness of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of relapsed/refractory extranodal NK/T cell lymphoma: a retrospective study of 17 patients.

The prognosis of extranodal nature killer (NK)/T cell lymphoma (ENKL) is dismal because of its aggressive course and multidrug resistance. Currently, for patients with relapsed/refractory ENKL, L-asparaginase-based regimens such as L-asparaginase, ifosfamide, methotrexate, etoposide, and dexamethasone (SMILE) or L-asparaginase, methotrexate, and dexamethasone (AspaMetDex) are recommended. We retrospectively investigated the efficacy and safety of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of 17 relapsed/refractory ENKL patients. Clinical data from these patients were collected and analyzed. The primary end point was overall response rate (ORR). All patients were subjected to 2 to 6 cycles of DDGP chemotherapy, and the median number of cycles of DDGP regimen administrated was four. The ORR was 88.2 % (15/17), with nine patients (52.9 %) achieved complete response (CR) and six patients (35.3 %) achieved partial response (PR). The median follow-up time was 17 months (range 2-28 months). The 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) were 82.4 and 64.7 %, respectively. For those CR responders, the median PFS was 17 months. Grade 3/4 neutropenia occurred in nine patients (52.9 %) and grade 3/4 thrombocytopenia occurred in six patients (35.3 %). DDGP combination chemotherapy produces favorable outcomes in relapsed/refractory ENKL, and more attention should be paid to treatment-related myelosuppression. Further prospective trials are expected to define the efficacy.

Effects of periodontal treatment on glycemic control in type 2 diabetic patients: a meta-analysis of randomized controlled trials.

The association between diabetes and inflammatory periodontal diseases has been studied extensively. However, there is a lack of robustness and homogeneity among studies describing effects of periodontal treatment on glycemic control. The aim of this study was to carry out a meta-analysis to understand whether periodontal treatment could improve glycemic control in type 2 diabetic patients. Electronic searches were carried out on MEDLINE, EMBASE and the Cochrane central register of controlled trials from 1980 to July 2012. Randomized controlled trials of periodontal therapy on glycemic control in diabetic patients with a minimum of 3 months of follow-up were included. Meta-analysis was carried out with 8 studies involving 515 participants using Stata 11.0 software. Our results showed that periodontal treatment could lead to a significant decrease in HbA1c level. The standardized mean difference between intervention groups and control groups was significant: 1.03% (95% confidence interval: 0.31% to 1.70%, P = 0.003) from baseline to 3 months, and 1.18% (95% confidence interval: 0.72% to 1.64%, P < 0.001) from baseline to 6 months. Periodontal treatment could lead to a non-significant decrease in fasting plasma glucose (FPG) levels from baseline to 3 months. The standardized mean difference between the intervention and the control group was 0.69 mg/dl (95% confidence interval: -0.27 mg/dl to 1.66 mg/dl, P = 0.158). Our analysis indicated that periodontal treatment could improve glycemic control in type 2 diabetic patients with periodontal diseases.

The long-term release and particle fracture behaviors of nanoplastics retained in porous media: Effects of surfactants, natural organic matters, antibiotics, and bacteria.

The transport of nanoplastics (NPs) in porous media has received a lot of attention, but the studies on the long-term release of NPs retained in porous media and the particle fracture during this process are seriously lacking. For filling this deficiency, we examined the individual or synergistic effects of surfactants, natural organic matters (NOMs), antibiotics, and bacteria on the desorption, long-term release, and particle fracture behaviors of polystyrene NPs (PS-NPs) retained in porous media. It was found that the change in hydrophilicity of PS-NPs dominated the long-term release of PS-NPs retained in porous media when surfactants were present. In the single system of surfactants and the dual system of surfactants and NOMs, the release of PS-NPs were improved owing to the increasing hydrophilicity of PS-NPs, although cationic surfactants also reduced the electrostatic repulsion between PS-NPs and porous media. Increasing antibiotic concentration reduced the electrostatic repulsion between PS-NPs and porous media to inhibit the release of PS-NPs. When bacteria were present whether containing antibiotics or not, the effects on roughness of PS-NPs dominated the release of PS-NPs. The effects of surfactants and NOMs on the PS-NP desorption were similar with the long-term release, with changes in hydrophilicity dominating the process. Whereas the effects of antibiotics and bacteria on the PS-NP desorption were different with the long-term release. Surfactants and NOMs in the presence of surfactants inhibited the fracture of PS-NPs by increasing the hydrophilicity of PS-NPs brought about the coating of water molecules on PS-NPs for protection. Antibiotics had no significant effects on the fracture of PS-NPs due to unaltered vertical forces on PS-NPs and no protective effect. Bacteria in the presence or absence of antibiotics inhibited the fracture of PS-NPs by coating PS-NPs retained in porous media to protect PS-NPs from fracture.

Quality of life in oral cancer patients-effects of tongue resection and sociocultural aspects.

BACKGROUND: The aims of this study were to evaluate postoperative quality of life in patients who have had resections of tongue cancer and reconstruction by flaps and to collect information about their sociocultural situation. METHODS: In this cross-sectional study, patients with primary tongue cancer treated with total and subtotal tongue resection in the First Affiliated Hospital of Zhengzhou University, between July 2008 and October 2011, were included. Quality of life was assessed by the 14-item Oral Health Impact Profile and the Medical Outcomes Study-Short Form 36 questionnaires 12 months postoperatively. Furthermore, a questionnaire about the sociocultural background of the patients was applied. RESULTS: Forty-six of the 62 questionnaires were returned (74.19%). In the Medical Outcomes Study-Short Form 36, the best-scoring domain was bodily pain, whereas the lowest scores were for social functioning and vitality. In the 14-item Oral Health Impact Profile, the lowest-scoring domain was psychological disability, followed by psychological discomfort and social disability. CONCLUSIONS: The postoperative quality of life in our patients was significantly influenced by tongue resection. This should be considered for surgical planning. The sociocultural data showed a rather low education level and life standard level for the majority of the patients.

Influences of input concentration, media particle size, metal cation valence, and ionic concentration on the transport, long-term release, and particle breakage of polyvinyl chloride nanoplastics in saturated porous media.

The environmental impact of nanoplastics has gradually attracted widespread attention; however, nanoplastics of polyvinyl chloride, one of the most commonly used plastics, have not yet been studied. In this study, we investigated the transport, long-term release behavior, and particle fracture of polyvinyl chloride nanoplastics (PVC NPs) in saturated quartz sand with different metal cations, ionic concentrations, input concentrations, and sand grain sizes by determining breakthrough, long-term release, and particle size distribution curves. The breakthrough curves and retention profiles were simulated by a mathematical model. The transport of PVC NPs increased with increased input concentration and sand grain size, which could be predicted by the Derjaguin-Landau-Verwey-Overbeek (DLVO) and colloid filtration theories. Increased ionic concentration and metal cation valence could restrain the transport of PVC NPs in saturated quartz sand owing to the decreased energy barrier between PVC NPs and sand grains. The total released amount of PVC NPs in the long-term release tests with different experimental conditions ranged from 3.91 to 21.95%. Increased sand grain size and decreased metal cation valence and ionic concentration resulted in an increased released amount of retained PVC NPs in saturated quartz sand, indicating increased release ability and mobility. The particle fracture results indicated that the PVC NPs were not broken down during long-term release under the experimental conditions of this research. This opens up a completely new and meaningful study of whether nanoplastics are broken down into smaller nanoplastics during their long-term release under various conditions.

A innovative stepwise strategy using magnetic Fe3O4-co-graft tannin/polyethyleneimine composites in a coupled process of sulfate radical-advanced oxidation processes to control harmful algal blooms.

A novel co-graft tannin and polyethyleneimine co-coating magnetic composite (TP@Fe3O4) was prepared in the study. On this premise, an unique stepwise efficient strategy based on magnetic flocculation and Sulfate radical (SO4•-)-advanced oxidation processes (S-AOPs) for eliminating Microcystis aeruginosa (M. aeruginosa) and algal organic matters (AOMs) was presented. Due to the high positive charge of TP@Fe3O4, a > 99 % high algae removal rate was obtained at a modest TP@Fe3O4 dosage of 100 mg/L at pH = 8.0 with a short separation time of 5 min. Further, peroxymonosulfate (PMS) treatment was employed as a pre-oxidation method to lower cell stability and promote M. aeruginosa removal by subsequent TP@Fe3O4 flocculation. The PMS/TP@Fe3O4 system successfully cuts the optimum dose of TP@Fe3O4 in half (50 mg/L) without causing obvious cell damage. Following algal fast magnetic separation, ultraviolet (UV) was introduced to activate PMS to totally degrade AOM and microcystin. Response surface methodology (RSM) demonstrated that UV/PMS oxidation removed > 80 % of DOC and > 94 % of microcystin under optimal conditions. SO4•- was the main radical species that aided in the elimination of AOM. This is the first study to use magnetic flocculation in conjunction with AOPs to mitigate harmful algal blooms, which can enable the non-destructive eradication of M. aeruginosa while also efficiently degrading AOMs.

Association of PM2.5 and its components with lengths of hospital stay for hand foot and mouth disease in children.

Hand foot and mouth disease (HFMD) is a widespread public health concern but the studies on air pollution and the lengths of hospital stay (LOS) of HFMD are scarce nevertheless. Clinic demographic features among 5135 hospitalized HFMD cases in Nanjing, China, had been characterized from 2012 to 2017. Then, we had analyzed the association between PM2.5 short-term exposure as well as its components (OM, BC, SO42-, NH4+, NIT, SOIL, and SS) and the LOS of HFMD. Among these cases that were involved in our study, 98.62% were aged 0-6 years old, and 3772 (73.46%) were hospitalized within 1 week or less. The LOS of HFMD patients was different in various age ranges, illness onset years, and illness onset seasons (P < 0.01). For per IQR increase in PM2.5 concentrations, LOS of HFMD increased by 0.52 (0.33, 0.71), 0.50 (95% CI, 0.31-0.69) and 0.46 (95% CI, 0.28-0.65) day in adjusted models at lag 3 days, lag 7 days, and lag 14 days, respectively. In addition, per IQR increase of BC, SO42-, NH4+, NIT, and SOIL was also significantly associated with the LOS of HFMD. Our findings corroborated that short-term PM2.5 exposure was associated with the increased LOS of HFMD, and its components (BC, SO42-, NH4+, NIT, and SOIL) of PM2.5 might play a key role in prolonged LOS of HFMD.

Utility of baseline, interim and end-of-treatment 18F-FDG PET/CT in extranodal natural killer/T-cell lymphoma patients treated with L-asparaginase/pegaspargase.

Positron emission tomography-computed tomography (PET/CT) is widely used for initial staging and monitoring treatment responses in Hodgkin and diffuse large B-cell lymphoma. However, its prognostic value in extranodal natural killer (NK)/T-cell lymphoma (ENKL) remains unclear. Here, we conducted a retrospective study to determine the impact of PET/CT in ENKL. Fifty-two patients newly diagnosed with ENKL were enrolled. Baseline maximum standardized uptake values (SUVmax), whole-body metabolic tumor volume (WBMTV) and whole-body total lesion glycolysis (WBTLG) were recorded. Additionally, interim PET/CT (I-PET) and end-of-treatment PET/CT (E-PET) results were scored using a 5-point scale. Patients were divided into groups using baseline parameter cut-off values; significant differences were found in overall survival (OS) and progression-free survival (PFS) between the high and low WBMTV and WBTLG groups and in OS between the two SUVmax groups. Positive I-PET and E-PET results predicted inferior PFS and OS. A multivariate analysis showed that baseline WBTLG, I-PET and E-PET results were associated with PFS and OS, and baseline SUVmax was an independent predictor of OS. Thus, baseline WBTLG, I-PET and E-PET results are good predictors of PFS and OS in ENKL patients who received L-asparaginase/pegaspargase in their first-line treatment, and baseline SUVmax is a valuable tool for assessing OS.

Transport, retention, and long-term release behavior of polymer-coated silver nanoparticles in saturated quartz sand: The impact of natural organic matters and electrolyte.

This study investigated the transport and long-term release of stabilized silver nanoparticles (AgNPs), including polyvinylpyrrolidone-coated AgNPs (PVP-AgNPs) and bare AgNPs (Bare-AgNPs), in the presence of natural organic matters (NOMs; both humic acids (HA) and alginate (Alg)) and an electrolyte (Ca2+) in a sand-packed column. Very low breakthrough rate (C/C0) of AgNPs (below 0.04) occurred in the absence of NOM and the electrolyte. Increasing the concentration of NOM and decreasing the influent NOM solution's ionic strength (IS) reduced the retention of AgNPs. The reduced NP retention at high NOM and low IS was mainly attributed to the increased energy barrier between the AgNPs and the sand grain surface. Notably, the retention of PVP-AgNPs was enhanced at high Alg concentration and low IS, which mainly resulted from the improved hydrophobicity that could increase the interaction between the PVP-AgNPs and the collector. The total release amount of PVP-AgNPs (10.03%, 9.50%, 28.42%, 6.37%) and Bare-AgNPs (3.28%, 2.58%, 10.36%, 1.54%) were gained when exposed to four kinds of NOM solutions, including deionized water, an electrolyte solution (1 mM Ca2+), HA with an electrolyte (1 mM Ca2+), and a Alg (40 mg/L) solution with an electrolyte (1 mM Ca2+). The long-term release of retained silver nanoparticles in the quartz sand was mostly through the form of released Ag NPs. The factors that increased the mobility of AgNPs in quartz sand could improve the release of the AgNPs. The release of AgNPs had no significant change in the presence Ca2+ but were increased in the presence of HA. The Alg slightly decreased the release of AgNPs by increasing the hydrophobicity of AgNPs. The results of the study indicated that all the tested NOM and Ca2+ have prominent influence on the transport and long-term release behavior of silver nanoparticles in saturated quartz sand.

Transport and long-term release behavior of polymer-coated silver nanoparticles in saturated quartz sand: The impacts of input concentration, grain size and flow rate.

This study investigated the transport and long-term release of stabilized poly vinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) in a quartz sand column with various sand grain sizes (0.3-0.5 µm, 0.5-1.0 µm, 1.0-2.0 µm), input concentrations of PVP-AgNP solution (1, 5, 15, 25 mg/L), and flow rates corresponding to a filter velocities (1.0, 1.5, 2.0, 2.5 mL/min-0.14, 0.21, 0.28, 0.35 cm/min) by determining breakthrough curves, retention profiles, and long-term release curves. Breakthrough curves and retention profiles were simulated by a mathematical model based on the advection dispersion equation coupled with second-order kinetics. The increased transport of PVP-AgNPs in quartz sand occurred with increased grain sizes and reduced input concentrations, and the transport can be predicted by the colloid filtration theory and DLVO theory. The long-term (one week) release amounts of retained PVP-AgNPs were 42.78%, 31.45%, and 10.95% in the fine, medium, and coarse sand columns, respectively, and were 34.70%, 40.79%, 47.24%, and 57.32% at flow rates of 0.0363, 0.0436, 0.0545, and 0.0726 mL/min, respectively. The released quantity of retained PVP-AgNPs decreased as the sand grain size increased. This phenomenon is opposite with the trend of increased transport of PVP-AgNPs with increased grain size in the transport test, which most likely because colloidal filtration regulates the transport process and adsorption (and desorption) dominates the release process. Increasing the flow rate increased the shear force on the particles, which improved the release of PVP-AgNPs. The results of the release tests further verified our previous published studies showing that the long-term release of retained PVP-AgNPs in the quartz sand was mostly in the form of released nanoparticles rather than ions. The results of this study indicated that sand grain size, input concentration, and flow rate have a prominent influence on the transport and long-term release behavior of PVP-AgNPs in saturated quartz sand.

S100A9 and ORM1 serve as predictors of therapeutic response and prognostic factors in advanced extranodal NK/T cell lymphoma patients treated with pegaspargase/gemcitabine.

Pegaspargase combined with gemcitabine have greatly improved the outcomes of advanced extranodal NK/T cell lymphoma (ENKL). However, patients frequently undergo recurrent disease due to chemoresistance, and few predictive parameters are available. The present study explored potential biomarkers to predict the therapeutic response of advanced ENKL treated with pegaspargase/gemcitabine and evaluate the prognostic significance. Through serum proteomic analysis, we identified 61 upregulated and 22 downregulated proteins in nonresponders compared with responders. We further validated that patients with unfavourable treatment outcomes displayed higher levels of S100A9 and ORM1 via enzyme-linked immunosorbent assay (ELISA). Moreover, the sensitivity and specificity for detecting refractory patients were 81.5% and 71.4% for S100A9 > 62 ng/ml, 85.2% and 77.1% for ORM1 > 1436 ug/ml, 100% and 57.1% for S100A9 combined with ORM1. Furthermore, in multivariate analysis elevated levels of S100A9 were associated with poor 2-year OS (40.2% vs. 76.6%, RR = 2.92, p = 0.005) and 2-year PFS (33.1% vs. 61.1%, RR = 2.61 p = 0.011). High ORM1 also predicted inferior 2-year OS (38.7% vs.76.1, RR = 2.46, p = 0.023) and 2-year PFS (18.4% vs. 73.2%, RR = 2.86, p = 0.009). Our results indicated that S100A9 and ORM1 could serve as reliable predictors of therapeutic response and independent prognostic factors of survival in advanced ENKL patients treated with pegaspargase/gemcitabine.

The DDGP (cisplatin, dexamethasone, gemcitabine, and pegaspargase) regimen for treatment of extranodal natural killer (NK)/T-cell lymphoma, nasal type.

Extranodal natural killer/T cell lymphoma (ENKL) is a high invasive disease with poor prognosis. Since there is no consensus on standard chemotherapy, we developed an original chemotherapeutic DDGP (cisplatin, dexamethasone, gemcitabine, and pegaspargase) regimen. We retrospectively analyzed 80 patients who received DDGP chemotherapy. The primary end point was progression-free survival (PFS) and secondary end points were overall survival (OS), complete response rate (CRR), and overall response rate (ORR). The one-year PFS and OS rates were 86.0% and 88.6%, and the 2-year PFS and OS rates were 81.40% and 87.1%, respectively. The ORR and CRR of DDGP chemotherapy were 91.3% and 60.0%. The major adverse events were myelosuppression, digestive tract toxicities, and coagulation disorder. No treatment-related deaths were observed. Our results suggest that the DDGP regimen is a high effective and safe treatment for ENKL.

DDGP versus SMILE in Newly Diagnosed Advanced Natural Killer/T-Cell Lymphoma: A Randomized Controlled, Multicenter, Open-label Study in China.

PURPOSE: Optimal treatment strategies for advanced natural killer/T (NK/T)-cell lymphoma have not been fully defined. We compared the safety and efficacy of DDGP and SMILE regimens for advanced NK/T-cell lymphoma in a randomized controlled, multicenter, and open-label clinical trial. EXPERIMENTAL DESIGN: Patients were newly diagnosed in stages III-IV and had performance scores in 0 to 2. Six cycles of DDGP (dexamethasone, cisplatin, gemcitabline, and pegaspargase) or SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy were randomly assigned to them. The primary end point was progression-free survival (PFS). Secondary end points included response rate and overall survival (OS). The trial is ongoing and is registered with ClinicalTrials.gov (No. NCT01501149). RESULTS: Of 42 patients enrolled, 21 were treated with DDGP therapy, and 21 patients were treated with SMILE therapy. The 1-year PFS and 2-year OS rates were better in the DDGP group than that in the SMILE group (86% vs. 38% for 1-year PFS, P = 0.006; 74% vs. 45% for 2-year OS, P = 0.027). Complete remission (CR) rate and overall response rate (ORR) of the DDGP group were higher than that in the SMILE group (71% vs. 29%, P = 0.005 for CR rate; 95% vs. 67%, P = 0.018 for ORR). The SMILE group showed more serious leucopenia (P = 0.030) and severe allergic reaction (P = 0.015) than the DDGP group. In addition, two cases in the SMILE group underwent grade 4 mucosal reaction. CONCLUSIONS: DDGP chemotherapy resulted in significant improvement in PFS, OS, and better tolerability compared with SMILE chemotherapy for newly diagnosed advanced NK/T-cell lymphoma patients. Clin Cancer Res; 22(21); 5223-8. ©2016 AACR.

Efficacy and safety of cisplatin, dexamethasone, gemcitabine and pegaspargase (DDGP) regimen in newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma: interim analysis of a phase 4 study NCT01501149.

To explore a more effective treatment for newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), we conducted a phase 4 study of the cisplatin, dexamethasone, gemcitabine, pegaspargase (DDGP) regimen. The primary end point was the 2-year progression-free survival (PFS) after the protocol treatment. Secondary endpoints included response rate (RR), overall survival (OS) and median survival time (MST). The interim analysis included data only from March 2011 to September 2013, who received six cycles of DDGP chemotherapy. A total of 25 eligible patients were enrolled. Seventeen patients (17/24, 70.83%) achieved complete response (CR) and four (4/24, 16.67%) achieved partial response (PR), three (3/24, 12.50%) had progressive disease (PD). The RR after treatment was 87.50%. After a median follow-up duration of 24.67 months (range 4-48 months). The 2-year PFS and OS rate were 61.80% (95% CI, 42.00% to 81.60%) and 68.50 % (95% CI, 48.70% to 88.30%), respectively. The MST was 36.55 months (95% CI, 29.41 months to 43.70 months). Grade 3/4 leukopenia occurred in fourteen patients (58.33%) and grade 3/4 thrombocytopenia occurred in eleven patients (45.83%). Twelve patients (50.00%) experienced Activated Partial Phromboplastin Ptime (APTT) elongation and fourteen patients (58.33%) experienced hypofibrinogenemia. In conclusion, DDGP regimen is an effective and tolerated treatment for newly diagnosed, advanced-stage ENKTL. This trial was registered at www.ClinicalTrials.gov as #NCT01501149.

Directing adult human periodontal ligament-derived stem cells to retinal fate.

PURPOSE: To investigate the retinal fate competence of human postnatal periodontal ligament (PDL)-derived stem cells (PDLSC) through a directed differentiation mimicking mammalian retinogenesis. METHODS: Human teeth were collected from healthy subjects younger than 35 years old. Primary PDLSC were isolated by collagenase digestion and cultivated. PDLSC at passage 3 were cultured in the induction media containing Noggin (antagonist of bone morphogenic protein) and Dkk-1 (antagonist of Wnt/ß-catenin signaling). Gene expression of neural crest cells, retinal progenitors, and retinal neurons, including photoreceptors, was revealed by RNA analyses, immunofluorescence, and flow cytometry. The neuronal-like property of differentiated cells in response to excitatory glutamate was examined by fluo-4-acetoxymethyl calcium imaging assay. RESULTS: Primary human PDLSC stably expressed marker genes for neural crest (Notch1, BMP2, Slug, Snail, nestin, and Tuj1), mesenchymal stem cell (CD44, CD90, and vimentin), and embryonic stem cell (c-Myc, Klf4, Nanog, and SSEA4). Under low attachment culture, PDLSC generated neurospheres expressing nestin, p75/NGFR, Pax6, and Tuj1 (markers of neural progenitors). When neurospheres were plated on Matrigel-coated surface, they exhibited rosette-like outgrowth. They expressed eye field transcription factors (Pax6, Rx, Lhx, Otx2). By flow cytometry, 94% of cells were Pax6(nuclear)Rx(+), indicative of retinal progenitors. At prolonged induction, they expressed photoreceptor markers (Nrl, rhodopsin and its kinase) and showed significant responsiveness to excitatory glutamate. CONCLUSIONS: Primary human PDLSC could be directed to retinal progenitors with competence for photoreceptor differentiation. Human neural crest-derived PDL is readily accessible and can be an ample autologous source of undifferentiated cells for retinal cell regeneration.