An ssDNA aptamer specific for detection and purification of hexahistidine-tagged proteins.

Aptamers are small-sized RNA or ssDNA ligands with a unique structure, which have high specificity and affinity to their cognate targets. Thus, in addition to the extensive values in various bio-medical fields, aptamers can also be alternatively used as affinity ligands in the bioprocess, such as for protein purification. In the present study, a hexahistidine specific aptamer named AptHis-C, was developed through the SELEX methodology, which has high affinity to hexahistidine, and its dissociation constant was as low as 20.8 nM. The structural prediction revealed that AptHis-C contains two connected stem-loop conformations. AptHis-C can only specifically recognize recombinant proteins with the hexahistidine-tag in simple or complex situations, and not to those with other tags. When immobilized on magnetic beads, AptHis-C can be used as a tool for hexahistidine-tagged recombinant protein purification. Its effectiveness is as good as traditional Ni-based beads. Besides, due to the intrinsic characteristics of nucleic acids, such as high thermal/chemical stability, immobilized aptamer-magnetic beads can be reused many times without an obvious decrease of purification effectiveness. This aptamer may represent a novel method for the detection and purification of hexahistidine-tagged recombinant proteins.

Neoadjuvant dose-modified docetaxel in squamous cell carcinoma of the head and neck: A phase 3 study.

OBJECTIVE: To evaluate the efficacy and safety of dose-modified docetaxel plus cisplatin and 5-fluorouracil (TPF) in Chinese patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: This Phase III, open-label, multi-center study included Chinese adults with previously untreated TNM Stage III or IV SCCHN (NCT00995293). Patients were randomized (1:1) to induction chemotherapy with TPF (docetaxel 60 mg/m2 and cisplatin 60 mg/m2 on day 1 and 5-FU 750 mg/m2  per day continuous IV infusion on days 1-5) or PF (cisplatin 75 mg/m2 on day 1 and 5-FU 750 mg/m2  per day on days 1-5) every 3 weeks for 3-4 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Median PFS in the TPF (n = 108) and PF (n = 111) groups was 400 days and 342 days (HR = 0.75; 95% CI, 0.53─1.06; p = .227), respectively. Overall response rate was higher for TPF versus PF (76.3% vs. 52.9%; p = .001), although this equalized following radiotherapy (75.0% vs. 73.9%). In the TPF and PF groups, ≥1 treatment-emergent adverse event was experienced by 104 (94.5%) and 110 (93.2%) patients, respectively. CONCLUSION: Adding dose-modified docetaxel to PF did not significantly improve PFS but may increase anti-tumor activity in Chinese patients with locally advanced SCCHN.

Investigation of expressions of PDK1, PLK1 and c-Myc in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Because the prognosis of DLBCL patients varies considerably, there is an urgent need to identify novel prognostic factors. In this study, we investigated the expression levels of the signalling enzyme 3-phosphoinositide-dependent protein kinase-1 (PDK1), the cell cycle regulatory enzyme Polo-like kinase 1 (PLK1) and the transcription factor (c-Myc) in DLBCL tissues and evaluated their clinical and prognostic significance. PDK1, PLK1 and c-Myc were detected by immunohistochemical staining of paraffin-embedded specimens from 152 DLBCL and 48 lymphadenitis patients. Expression levels were correlated with clinicopathological factors. PDK1, PLK1 and c-Myc were more commonly expressed in DLBCL specimens than in lymphadenitis specimens, and the expression of each protein correlated positively with that of the other two molecules. High PDK1, PLK1 and c-Myc expression, high international prognostic index score, high lactate dehydrogenase levels and late Ann Arbor stage were shown to correlate with shorter overall survival time. A multivariate Cox regression model showed that high expression levels of PLK1 and c-Myc were independent prognostic factors for DLBCL. Our findings indicate that PLK1 and c-Myc expression might be promising predictive biomarkers for DLBCL patients.

Inhibition of Aurora Kinase A Induces Necroptosis in Pancreatic Carcinoma.

BACKGROUND & AIMS: Induction of nonapoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2.03, CFPAC1, MiaPaCa2, BxPc3, and PANC02) and the HEK293 cell line, measuring loss of plasma membrane integrity, gain in cell volume, swollen organelles, and cytoplasmic vacuoles. We tested the effects of CCT137690 in colon formation assays, and the effects of the necroptosis (necrostatin-1 and necrosulfonamide), apoptosis, autophagy, and ferroptosis inhibitors. We derived cells from tumors that developed in Pdx1-Cre;K-RasG12D/+;p53R172H/+ (KPC) mice. Genes encoding proteins in cell death pathways were knocked out, knocked down, or expressed from transgenes in PDAC cell lines. Athymic nude or B6 mice were given subcutaneous injections of PDAC cells or tail-vein injections of KPC tumor cells. Mice were given CCT137690 (80 mg/kg) or vehicle and tumor growth was monitored; tumor tissues were collected and analyzed by immunohistochemistry. We compared gene expression levels between human pancreatic cancer tissues (n = 130) with patient survival times using the online R2 genomics analysis and visualization platform. RESULTS: CCT137690 induced necrosis-like death in PDAC cell lines and reduced colony formation; these effects required RIPK1, RIPK3, and MLKL, as well as inhibition of aurora kinase A (AURKA). AURKA interacted directly with RIPK1 and RIPK3 to reduce necrosome activation. AURKA-mediated phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) at serine 9 inhibited activation of the RIPK3 and MLKL necrosome. Mutations in AURKA (D274A) or GSK3ß (S9A), or pharmacologic inhibitors of RIPK1 signaling via RIPK3 and MLKL, reduced the cytotoxic activity of CCT137690 in PDAC cells. Oral administration of CCT137690 induced necroptosis and immunogenic cell death in subcutaneous and orthotopic tumors in mice, and reduced tumor growth and tumor cell phosphorylation of AURKA and GSK3ß. CCT137690 increased survival times of mice with orthotopic KPC PDACs and reduced tumor growth, stroma, and metastasis. Increased expression of AURKA and GSK3ß mRNAs associated with shorter survival times of patients with pancreatic cancer. CONCLUSIONS: We identified the aurora kinase inhibitor CCT137690 as an agent that induces necrosis-like death in PDAC cells, via RIPK1, RIPK3, and MLKL. CCT137690 slowed growth of orthotopic tumors from PDAC cells in mice, and expression of AURKA and GSK3ß associate with patient survival times. AURKA might be targeted for treatment of pancreatic cancer.

Efficacy and tolerance of GELOXD/P-GEMOXD in newly diagnosed nasal-type extranodal NK/T-cell lymphoma: A multicenter retrospective study.

OBJECTIVES: Nasal-type extranodal natural killer NK/T-cell lymphoma (ENKTCL) is a distinct type of non-Hodgkin lymphoma with poor prognosis. This research aimed to evaluate the efficacy and safety of the GELOXD or P-GEMOXD regimens in patients with ENKTCL. METHODS: Newly diagnosed ENKTCL patients treated with either the GELOXD or the P-GEMOXD regimen were identified from three cancer centers between January 2010 and December 2016. Kaplan-Meier and Cox regression analyses were used to calculate overall survival (OS) and progression-free survival (PFS) and to investigate prognostic factors. RESULTS: One hundred and eighty-four cases were identified from three cancer centers. After 1-5 treatment cycles of GELOXD or P-GEMOXD chemotherapy, 155 (84%) patients showed a complete response (CR). The 3-year OS (73.0% vs 38.2%, P = .001) and PFS (72.8% vs 32.4%, P = .000) rates were significantly higher in early-stage patients compared with advanced-stage patients. A multivariate analysis revealed that patient CR status was a significant independent factor in disease prognosis. Grade 3/4 leukopenia occurred in 43 (23.4%) patients. Major non-hematological toxicities included nausea (n = 117, 63.6%) and vomiting (n = 66, 35.9%). CONCLUSIONS: The GELOXD and P-GEMOXD chemotherapy regimens are well tolerated and provide favorable survival outcomes in patients with ENKTCL.

Short-Course Versus Long-Course Chemoradiotherapy for Stage IE-IIE Extranodal Natural Killer/T cell Lymphoma, Nasal Type: A Multicenter Retrospective Study.

BACKGROUND This study compared clinical outcomes and adverse events between L-asparaginase/pegaspargase-based short-course and long-course chemoradiotherapy in newly diagnosed stage IE-IIE extranodal natural killer/T cell lymphoma, nasal type (ENKTL). MATERIAL AND METHODS Patients were categorized into a short-course (2-4 chemotherapy cycles, median: 4, n=153) and long-course group (5-6 cycles, median: 6, n=83). The chemotherapy regimens included GELOX, SMILE, and VLP. The radiotherapy dose was 40-63 Gy (median: 55 Gy). Adverse events, treatment responses, and survival outcomes between the 2 groups were compared. RESULTS Ann Arbor stage IIE and short-course chemotherapy adversely affected overall survival (OS). Ann Arbor stage IE favorably affected progression-free survival (PFS). Grade 3-4 hematological toxicities were higher in the long-course group (25.3% vs. 14.4%, p=0.038). Ann Arbor stage was the single different clinical feature between the 2 groups, and independently affected survival outcomes. In subgroup analysis of stage IE, there was no difference in response rates and survival outcomes between the 2 groups. In subgroup analysis of stage IIE, the recurrence and death rates were significantly lower in the long-course group (6.1% vs. 23.2%, p=0.015; 12.2% vs. 39.3%, p=0.002; respectively), and the 3-year OS and PFS rates were much longer in the long-course group (87.8% vs. 62.5%, p<0.001; 83.7% vs. 57.1%, p=0.001; respectively). CONCLUSIONS When radiotherapy was combined with L-asparaginase/pegaspargase-based chemotherapy to treat early-stage ENKTL patients, 2-4 cycles of chemotherapy might be sufficient for stage IE patients, while stage IIE patients might require 5+ cycles.

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells.

BACKGROUND/AIMS: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. METHODS: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53). RESULTS: Mutant p53 cells exhibited increased expression of the C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and inositol-requiring enzyme-1α (IRE1α). The Mutant p53 cells were also found to be sensitive to chemotherapy and displayed decreased expression of PI3K, Akt, and mTOR. The mutant p53 cell lines were treated with tunicamycin to induce ERS and rapamycin in order to inhibit mTOR. Both agents increased the expression of CHOP, GRP78, IRE1α, LC3-II/LC3-I, Atg5, Atg7, caspase-3, caspase-12, cleaved caspase-3, cleaved caspase-12, as well as decreases in cell proliferation as well as the expression levels of PI3K, Akt, and mTOR. Enhanced levels of cell apoptosis and reduced chemotherapy resistance were also detected. CONCLUSION: The findings of our study suggest that ERS promotes autophagy and apoptosis, while acting to reduce chemotherapy resistance in mutant p53 LC cells by downregulating the PI3K/Akt/mTOR signaling pathway.

STAT3 mediates multidrug resistance of Burkitt lymphoma cells by promoting antioxidant feedback.

Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm. Although BL is relatively sensitive to chemotherapy, some patients do not respond to initial therapy or relapse after standard therapy, which leads to poor prognosis. The mechanisms underlying BL chemoresistance remain poorly defined. Here, we report a mechanism for the relationship between the phosphorylation of STAT3 on Tyr705 and BL chemoresistance. In chemoresistant BL cells, STAT3 was activated and phosphorylated on Tyr705 in response to the generation of the reactive oxygen species (ROS), which induced Src Tyr416 phosphorylation after multi-chemotherapeutics treatment. As a transcription factor, the elevated phosphorylation level of STAT3Y705 increased the expression of GPx1 and SOD2, both of which protected cells against oxidative damage. Our findings revealed that the ROS-Src-STAT3-antioxidation pathway mediated negative feedback inhibition of apoptosis induced by chemotherapy. Thus, the phosphorylation of STAT3 on Tyr705 might be a target for the chemo-sensitization of BL.

WITHDRAWN: ALDH1A1 induces resistance to CHOP in diffuse large B-cell lymphoma through activation of the JAK2/STAT3 pathway.

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Identification of baicalein as a ferroptosis inhibitor by natural product library screening.

Ferroptosis, a novel form of regulated cell death, is characterized by oxidative injury from iron accumulation and lipid peroxidation. In a natural product library screening for ferroptosis inhibitor, we found that baicalein is a potent inhibitor of erastin-induced ferroptosis in pancreatic cancer cells. Baicalein (also termed 5,6,7-trihydroxyflavone) is a flavonoid originally obtained from the roots of Scutellaria baicalensis and Scutellaria lateriflora. We showed that baicalein exhibits remarkable anti-ferroptosis activity compared with well-known ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, deferoxamine mesylate, and ß-mercaptoethanol. At the biochemistry level, baicalein limits erastin-induced ferrous iron production, glutathione depletion, and lipid peroxidation. At the protein level, baicalein suppresses erastin-mediated degradation of glutathione peroxidase 4, a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation. Thus, baicalein enhances cellular anti-ferroptosis capacity and could be a potential therapeutic agent for ferroptosis-associated tissue injury.

Inhibition of microRNA-196a might reverse cisplatin resistance of A549/DDP non-small-cell lung cancer cell line.

We aimed to explore the possible mechanism of microRNA-196a (miR-196a) inhibition and reversion of drug resistance to cisplatin (DDP) of the A549/DDP non-small-cell lung cancer (NSCLC) cell line. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect expression differences of miR-196a in the drug-resistant A549/DDP NLCLC cell line and the parental A549 cell line, and expressions of miR-196a in the A549/DDP NLCLC cell line transfected with miR-196a inhibitor (anti-miR-196a group) and the miR-196a negative control (miR-NC) group and blank group (without transfection). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was applied in examining the cell viability of A549/DDP cell line before and after transfection. Clonogenic assay was used to detect cell proliferation ability. Flow cytometry was applied in detecting apoptosis rate of assayed tumor cell and rhodamine-123 changes in cells. Western blot was applied in detecting proteins of drug-resistant related gene in A549/DDP cell line. Significantly higher expression of miR-196a was detected in the drug-resistant A549/DDP cell line than that in the parental A549 cell line (P < 0.05). However, miR-196a expression in the anti-miR-196a group decreased obviously compared to that in the blank group and the miR-NC group (both P < 0.05); The value of IC50 in the anti-miR-196a group showed remarkably lower than that in the blank group and the miR-NC group (both P < 0.05); Rh-123 absorbing ability in the anti-miR-196a group increased 2.51 times and 2.49 times respectively compared to that in the blank group and the miR-NC group (both P < 0.05). No statistical differences in the apoptosis rate of A549/DDP cell line in the early stage were found among the three groups (all P > 0.05), but the late-stage apoptosis rate in the anti-miR-196a group was significantly higher than that in the blank group and the miR-NC group (both P < 0.05); The expressions of human multidrug resistance 1 (MDR1), multidrug resistance protein 1 (MRP1), excision repair cross-complementation 1 (ERCC1), survivin, and B cell lymphoma 2 (Bcl-2) decreased significantly while RhoE increased significantly in the anti-miR-196a group than the blank group and the miR-NC group (all P < 0.05). Inhibition of miR-196a could reverse cisplatin resistance of A549/DDP cell lines, which might relate with inhibition of drug efflux, down-regulation of drug-resistant protein expression, cell apoptosis, and cell proliferation suppression.

Multiple Roles of WNT5A in Breast Cancer.

Breast cancer is one of the most common malignant tumors of women. Modern combinatorial therapeutic regimens can reduce patient tumor burdens to undetectable levels, yet in many cases these tumors will relapse. Understanding of breast cancer biology, developing more potent therapeutic approaches, and overcoming resistance are of great importance. WNT5A is a non-canonical signaling member of the WNT family. Its role in breast cancer still remains unclear. Most of the evidence shows that WNT5A is a suppressor in breast cancer and loss of its expression is associated with poor prognosis, while some evidence suggests the tumorigenicity of WNT5A. WNT signaling molecules are potent targets for treatment of cancer. Therefore, understanding the role of WNT5A in breast cancer may provide new ideas and methods for breast cancer treatment. We review the evidence concerning WNT5A and breast cancer involving the signaling pathways and the molecular-targeted therapy of WNT5A. Our results show that the role WNT5A plays depends on the availability of key receptors and intercellular interactions among different cell types.

ALDH1A1 mediates resistance of diffuse large B cell lymphoma to the CHOP regimen.

Although there have been substantial advances in our knowledge of the resistance of diffuse large B cell lymphoma (DLBCL) to chemotherapy, there are few efficient treatment strategies for recurrent/refractory DLBCL. The aim of this study was to investigate the role of aldehyde dehydrogenase (ALDH) 1A1 in the resistance of diffuse large B cell lymphoma to the chemotherapeutic mixture consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). The involvement of ALDH1A1 in DLBCL was elucidated by knockdown and pharmacologic inhibition; Cell Counting Kit-8 (CCK-8) and clone formation assays were used to determine its role in CHOP sensitivity and clone formation ability. Caspase colorimetric assay was used to measure the extent of apoptosis. Western blot analysis was used to measure signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa B (NF-κB) signaling proteins, and quantitative real-time PCR (RT-PCR) was used to measure the differential expression of ALDH1A1 of DLBCL patients and healthy donors. ALDH1A1 showed a 5.64-fold higher expression in malignant B cells than in normal B cells. Diethylaminobenzaldehyde (DEAB) decreased the half maximal inhibitory concentration (IC50) of the CHOP regimen in Farage cells from 344.78 ± 65.75 to 183.88 ± 49.75 ng/ml (P = 0.004). Both knockdown and inhibition of ALDH1A1 reduced clonogenicity, increased caspase-3/caspase-9 activity, and attenuated the phosphorylation status of STAT3/NF-κB. The prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels of expression (P = 0.044). ALDH1A1 is a new mediator for resistance of DLBCL to CHOP; it is a predictor of clinical prognosis and may serve as a potential target to improve chemotherapy responsiveness of human DLBCL.

miR-217 inhibits invasion of hepatocellular carcinoma cells through direct suppression of E2F3.

The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to the development of invasion and metastasis. Recent data strongly suggests the important role of miRNAs in cancer progression, including invasion and metastasis. Here, we found miR-217 expression was much lower in highly invasive MHCC-97H HCC cells and metastatic HCC tissues. Restored miR-217 expression with miR-217 mimics inhibited invasion of MHCC-97H cells. Inversely, miR-217 inhibition enhanced the invasive ability of Huh7 and MHCC-97L cells. Mechanically, bioinformatics analysis combined with experimental analysis demonstrated E2F3 was a novel direct target of miR-217. Moreover, E2F3 protein level was positively associated with HCC metastasis and functional analysis confirmed the positive role of E2F3 in HCC cell invasion. Our findings suggest miR-217 function as a potential tumor suppressor in HCC progression and miR-217-E2F3 axis may be a novel candidate for developing rational therapeutic strategies.

Hypercoagulability in cancer patients grouped by syndromes differentiated with the theory of abnormal hilit in traditional Uyghur medicine.

OBJECTIVE: To investigate the relationship in malignant-neoplasm patients of hypercoagulability between syndromes differentiated with the theory of abnormal hilit in traditional Uyghur medicine (TUM). METHODS: A total of 248 patients with malignant tumors were enrolled. Based on the theory of TUM they were divided into two groups: abnormal Savda and abnormal Non-Savda (including abnormal Khan, abnormal Sepra and abnormal Belghem types); fifty healthy volunteers were selected as controls. Platelet (PLT), prothrombin time (PT), plasma fibrinogen (FIB), thrombin time (TT), activated partial thromboplastin time (aPTT) and D-Dimer (D-D) were measured in both groups. RESULTS: Compared with the control and abnormal Non-Savda groups, in the abnormal Savda group the PLT count increased (P < 0.05), the PT was lengthened (P < 0.01), and the FIB significantly increased (P < 0.01). D-Ds in the three groups were significantly different (P < 0.05). No significant difference was found in TT and aPTT values (P > 0.05). CONCLUSION: Hypercoagulability existed in patients with malignant tumors in the different types of TUM syndromes, especially in the abnormal Savda group; this was characterized by increased blood viscosity, platelet aggregation and thrombosis. D-D appears to be a significant predictor for the therapeutic effect of TUM in relation to malignant tumor therapies.

[Metabolic changes in abnormal savda patients with different types of tumor: a clinical observation].

OBJECTIVE: To explore in vivo metabolic changes in abnormal savda patients with different types of tumor. METHODS: A total of 142 abnormal savda patients with common cancer types were enrolled in this study, and 50 healthy volunteers were recruited as the control group. For each sample, the H Nuclear Magnetic Resonance (NMR) based metabonomic analysis was performed. The free attenuation signal was computed subsection integral. Data obtained were analyzed by the Orthogonal Partial Least-Squares Discriminant Analysis (OPLS-DA). RESULTS: Compared with the control group, leucine, isoleucine, valine, histidine, phenylalanine, tyrosine, alanine, creatine, lactic acid, inositol, alpha-and beta-glucose, unsaturated lipids, very low density lipoprotein (VLDL) significantly decreased (P <0.05), while glycoprotein and carnitine significantly increased (P <0. 05) in the abnormal Savda group. CONCLUSION: Abnormal savda patients with different types of tumor had similar metabonomics changes.

Treatment of Abdominal Desmoplastic Small Round Cell Tumor Induces Acute Myeloid Leukemia-M5: A Case Report and Literature Review.

Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive malignancy. Most patients are diagnosed at a late stage with poor prognosis. The treatment usually includes combined intensive chemotherapy, cytoreductive surgery, radiotherapy, and targeted therapy. Due to the low incidence rate and dismal survival, there is currently a lack of case reports on DSRCT with concurrent leukemia. We report a case of a young patient who achieved disease stabilization for 14 months after receiving 6 cycles of chemotherapy and whole abdominal radiation therapy (WART), followed by consolidation treatment with anlotinib. However, the treatment was terminated due to the development of Acute Myeloid Leukemia-M5 (AML-M5). Multimodal therapy may provide a survival benefit for rare tumors that lack standard treatment. However, intensive chemotherapy and extensive radiotherapy carry a risk of inducing secondary malignancies. This is the first reported case of concurrent DSRCT and AML-M5 with short intervals between onset.

Increased coexpression of PD-L1 and IDO1 is associated with poor overall survival in patients with NK/T-cell lymphoma.

Immunotherapy with programmed cell death 1 ligand 1 (PD-L1) blockade was effective in patients with NK/T-cell lymphoma. In addition to PD-L1, indoleamine 2,3-dioxygenase-1 (IDO1) is one of the most promising immunotherapeutic targets. High proportions of PD-L1 and IDO1 proteins were observed by immunohistochemistry (IHC) from 230 newly diagnosed patients with NK/T lymphoma with tissue samples from three cancer centers and were associated with poor overall survival (OS) in patients with NK/T lymphoma. Importantly, the coexpression of PD-L1 and IDO1 was related to poor OS and short restricted mean survival time in patients with NK/T lymphoma and was an independent prognostic factor in the training cohorts, and which was also validated in 58 NK/T lymphoma patients (GSE90597). Moreover, a nomogram model constructed with PD-L1 and IDO1 expression together with age could provide concise and precise predictions of OS rates and median survival time. The high-risk group in the nomogram model had a positive correlation with CD4 + T-cell infiltration in the validation cohort, as did the immunosuppressive factor level. Therefore, high PD-L1 and IDO1 expression was associated with poor OS in patients with NK/T lymphoma. PD-L1 and IDO1 might be potential targets for future immune checkpoint blockade (ICB) therapy for NK/T lymphoma.

Diagnostic accuracy of circulating tumor cells detection in gastric cancer: systematic review and meta-analysis.

BACKGROUND: Circulating tumor cells (CTCs) detection has previously been used for diagnosing gastric cancer. However, the previous studies failed to make an agreement whether the detection of CTCs contributes to the diagnosis of gastric cancer. METHODS: A systematic review and meta-analysis was performed to evaluate the overall accuracy of CTCs detection for diagnosing gastric cancer. PubMed, Embase and the Wanfang database were searched in all languages published up to Oct 2012. The pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic odds ratio (DOR) and summary receiver operating characteristic (sROC) curve were calculated to evaluate the overall test performance. RESULTS: Twenty studies were included in this systematic review and meta-analysis. The diagnostic value of CTCs detection for the gastric cancer was calculated to evaluate the overall test performance. The summary estimates of The pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio were 0.42 (95% confidence interval (CI), 0.21-0.67), 0.99 (95% CI, 0.96-1.00), 58.2 (95% CI, 9.8-345.9), 0.58 (95% CI, 0.38-0.89), and 100 (95% CI, 15-663), respectively. The summary receiver operating characteristic curve was 0.97 (95% CI, 0.95-0.98). Deek's funnel plot asymmetry test found no evidence of study publication bias in the current study (P = 0.49). CONCLUSION: This systematic review suggests that CTCs detection alone cannot be recommended as a screening test for gastric cancer. However, it might be used as a noninvasive method for the confirmation of the gastric cancer diagnosis.

Facile synthesis of monodispersed Fe2O3 nanoparticles and its cellular uptake and cytotoxicity studies.

Monodispersed Fe2O3 nanoparticles were fabricated with a facile hydrothermal synthetic route by using Fe(NO3)3 x 7H2O and glycin as reagents without using any templates or surfactants in this report. The prepared nanoparticles were pure hexagonal alpha-Fe2O3 particles from the characterization of XRD analysis. The Fe2O3 nanoparticles with a narrow size distribution and a mean diameter of - 50 nm can be well dispersed in water. Cellular uptake and cellular responses of the as-prepared Fe2O3 nanoparticles for human cancer cells have been studied. The Fe2O3 nanoparticles can be readily uptake by the cells, but no obvious oxidative damages in the cells can be detected after an incubation of 24 h. Also the treatment of Fe2O3 nanoparticles did not induce any changes in cell viability and cell proliferation. These results demonstrate that the Fe2O3 nanoparticles prepared with our method are remarkably biocompatible, which can be used as a substitute with high biosafety for the present iron oxides materials in different kinds of applications.