Extranodal natural killer/T-cell lymphoma is an aggressive Epstein-Barr virus-associated lymphoma with poor outcomes in advanced-stage disease. High-dose methotrexate-containing, asparaginase-based regimens induce responses but are limited by toxicity, and lower-intensity alternatives show suboptimal durability. We conducted a prospective, multicenter, single-arm phase II trial of the LEAP regimen in newly diagnosed stage IV disease. Eligible patients had ECOG 0-3 and were >65 years or ≤65 years with contraindications to high-dose methotrexate. Treatment comprised up to eight 21-day cycles of sintilimab 200 mg (day 1), pegaspargase 2500 IU/m2 (day 1), and anlotinib 8 mg (days 1-14), with autologous hematopoietic stem cell transplantation (auto-HSCT) allowed for complete responders at the investigator's discretion and patient's preference. Thirty-seven patients were enrolled (median age 64; range, 32-78). At week 24, the complete remission (CR) was 72.9% (27/37), surpassing the prespecified 55% threshold. With a median follow-up of 48 months, estimated 4-year progression-free survival (PFS) and overall survival (OS) were 56.6% and 75.2%, respectively. Seventeen patients underwent auto-HSCT after achieving CR and had lower relapse (17.6% vs 60.0%) and improved PFS (Hazard Ratio=0.23; p<0.05) versus observation. Grade ≥3 adverse events were limited to neutropenia (10.8%) and hyperbilirubinemia (10.8%), with no treatment discontinuations for toxicity or treatment-related deaths. LEAP regimen produced high CR rates and durable survival with manageable toxicity in advanced-stage disease unsuitable for HD-MTX induction and may enable curative-intent therapy; randomized validation is warranted. The study was registered at ClinicalTrials.gov (NCT04004572).

In the published version of this article [1], it was identified that a mandatory section of the Supplementary Material and the List of Abbreviations were missing. To address this issue and ensure clarity and accuracy, the corrected version of the section is presented below. The original article can be found online at https://www.benthamscience.com/article/145711 Details of the error and the corrections are provided below. Corrected: LIST OF ABBREVIATIONS OMIM = Online Mendelian Inheritance in Man STRING = Search Tool for the Retrieval of Interacting Genes/Proteins TCMSP = Traditional Chinese Medicine Systems Pharmacology database SUPPLEMENTARY MATERIAL Supplementary material is available on the publisher’s website along with the published article. The publisher apologizes for any inconvenience caused.

Background: The prognostic superiority of preoperative chemoradiotherapy (pre-CRT) over preoperative chemotherapy (pre-CT) in patients with locally advanced gastric cancer remains controversial. Herein, we evaluated the efficacy and safety of pre-CRT relative to those of pre-CT in this cohort. Methods: This open-label, phase III, randomized controlled trial was conducted at 4 medical centers in China. Eligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma were randomly assigned (1:1) to receive either 3 cycles of oxaliplatin and S-1 (SOX), followed by surgery and 3 postoperative cycles of SOX (pre-CT), or 1 cycle of SOX, followed by concurrent chemoradiotherapy, a second cycle of SOX, surgery, and 3 postoperative cycles of SOX (pre-CRT). The primary endpoint was 3-year disease-free survival (DFS). Secondary endpoints included 3-year overall survival (OS), R0 resection rate, pathological complete response (pCR) rate, treatment-related toxicity, and postoperative complications. Results: Due to premature trial termination, only 204 patients were enrolled, and an efficacy analysis was conducted on 194 eligible patients. The baseline characteristics were well balanced between the 2 groups. The DFS and OS were indistinguishable between the 2 groups. The 3-year DFS rates were 53.6% in the pre-CRT group and 53.9% in the pre-CT group [hazard ratio (HR), 1.02; 95% confidence interval (CI), 0.70 to 1.50; log-rank P = 0.913]. The 3-year OS rates were 62.8% in the pre-CRT group and 60.5% in the pre-CT group (HR, 0.97; 95% CI, 0.63 to 1.47; log-rank P = 0.874). The R0 resection rates were 81.0% and 74.5% in the pre-CRT and pre-CT groups, respectively. Additionally, the pCR rate was higher in the pre-CRT group (12.0%) than in the pre-CT group (2.1%). Treatment-related toxic effects were comparable between the 2 groups. Conclusion: This trial did not demonstrate a survival advantage for pre-CRT over pre-CT in patients with locally advanced gastric or gastroesophageal adenocarcinoma.

Background: Combined asparaginase-based chemoradiotherapy for early-stage extranodal natural killer/T-cell lymphoma (NKTCL) is effective but often causes significant hematological toxicity and infection, compromising treatment delivery. We evaluated a chemotherapy-sparing induction regimen of camrelizumab, low-dose apatinib, and pegaspargase (CAPA) followed by sequential radiotherapy. Methods: In this multicentre, single-arm, phase 2 trial, adults with biopsy-confirmed nasal or upper aerodigestive tract NKTCL (WHO 2016; Lugano stage IE/IIE) received four 21-day cycles of CAPA followed by intensity-modulated radiotherapy (50–56 Gy). The primary endpoint was complete response (CR) at week 24 by Lugano 2014. Safety was assessed in all treated patients. Exploratory analyses examined interim response and plasma EBV DNA dynamics. Trial registration: NCT04366128. Findings: Between June 2020 and Oct 2022, 61 patients received CAPA; 54 (88·5%) had an evaluable week-24 assessment. Week-24 CR was 88.9% (48/54; 95% CI 77·4–95·8) and overall response was 92.6% (95% CI 82·1–97·9). At median follow-up 42.2 months (IQR 34·7–46·1), 2-year progression-free survival was 83·3% (95% CI 70·4–91·0) and overall survival was 88.9% (76·9–94·9). Grade 3–4 treatment-related adverse events occurred in 29 (47·5%) patients, mainly hypertriglyceridaemia (19·7%) and hypertension (11·5%); grade 3–4 neutropenia occurred in two (3·3%) and anaemia in one (1·6%), with no treatment-related deaths. Week-12 non-response (SD/PD) and lack of plasma EBV DNA clearance by week 24 (EBV-notclear) were associated with inferior survival. Interpretation: CAPA followed by sequential radiotherapy achieved high CR and durable disease control with minimal severe haematological toxicity in early-stage NKTCL, supporting comparative evaluation and prospective integration of PET-based response assessment and plasma EBV-DNA monitoring.

Shuanghuanglian (SHL) and its primary constituents have demonstrated protective effects against allergenic diseases. This review examines the anaphylactic and anti-allergenic activities of SHL and its constituents. We also discuss potential avenues for future research, particularly regarding the expansion of the clinical applications of SHL formulations (oral or nebulized) for the treatment of allergenic disorders. For this review, we searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases for relevant publications. Additionally, details of the essential active components and target genes of SHL were obtained from the Traditional Chinese Medicine Systems Pharmacology database (TCMSP), and information on allergy-related genes was collected from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Lists of both the SHL target and disease-related genes were imported into the 'Draw Venn Diagram' tool on the website (http://bioinformatics.psb.ugen /web tools/Venn/). A protein-protein interaction network for SHL and disease targets was constructed with reference to the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the potential pathways were identified based on Kyoto Encyclopaedia of Genes and Genome enrichment analyses. The allergenic reactions induced by SHL injection (intravenous) and its main constituents (intraperitoneal or intravenous injection) have been verified in animal experiments. Furthermore, the protective effects of SHL injection (intraperitoneal) and its individual Chinese herb components (intragastric administration), namely, Flos Lonicerae, Radix Scutellariae, and Fructus Forsythiae, as well as their main constituents (intraperitoneal or intragastric administration), have been verified in asthma, rhinitis, atopic dermatitis, and both IgE- and non-IgE-mediated systemic allergic responses. The network pharmacology analysis revealed that the therapeutic effects of SHL might be primarily mediated through the regulation of the IL-17 and TNF-α signalling pathways and Th17 cell differentiation. Accumulated research data provide a theoretical basis for the clinical application of SHL (via extravascular routes) in the treatment of allergenic diseases.

8581 Background: Although the ASTRUM-004 trial has confirmed that serplulimab plus platinum-based therapy improves survival in patients with locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC), evidence regarding its efficacy and safety in routine clinical practice remains limited. Previous results from the ASTRUM-004R trial have shown that a serplulimab plus platinum-based therapy exhibits promising antitumor activity in sqNSCLC. Here, we report the updated follow-up results from this study. Methods: The ASTRUM-004R trial is a retrospective, real-world study conducted across 14 centers in China. Patients with locally advanced or metastatic sqNSCLC received first-line serplulimab plus platinum-based therapy, followed by serplulimab maintenance treatment until disease progression, intolerable toxicity, or up to 2 years. This update presents the survival outcomes, including progression-free survival (PFS) and overall survival (OS). Additionally, PFS was assessed across various patient subgroups. Results: A total of 132 patients were enrolled in the analysis, with a median follow-up of 18 months as of October 31, 2025. The median patient age was 69 years. Overall, 92.4% (n = 122) were male, 71.2% (n = 94) were aged 65 or older, 19.7% (n = 26) had an ECOG performance status of 2, and 47.0% (n = 62) had stage IV disease. Maintenance therapy was administered to 50.8% (n = 67) of the patients. The median PFS for all patients was 14.8 months (95% CI: 11.9-19.6), with a 6-month PFS rate of 78.5% (95% CI: 71.5%-86.2%). The median PFS benefit was comparable between patients receiving nab-paclitaxel and those receiving paclitaxel (17.5 vs. 15.2 months, P = 0.677), suggesting no significant difference in efficacy between the two groups. Furthermore, a significantly longer median PFS was observed in patients with stage III disease compared to those with stage IV disease (20.4 vs. 11.9 months, P = 0.009). The median OS for all patients was 29.7 months (95% CI: 29.7-NR), with a 12-month OS rate of 90.1% (95% CI: 84.7%-95.9%). The updated findings confirm sustained antitumor activity, as evidenced by an objective response rate of 66.7% (95% CI: 57.9%-74.6%) and a disease control rate of 95.5% (95% CI: 90.4%-98.3%). Adverse events (AEs) of any grade occurred in 48 patients (36.4%), most of whom had hematological disorders. Immune-related AEs (irAEs) were reported in 35 patients (26.5%), including 9 (6.8%) who experienced grade ≥3 irAEs. Conclusions: Updated results from the ASTRUM-004R study show that first-line serplulimab platinum-based therapy provides a significant survival benefit with a manageable safety profile in locally advanced or metastatic sqNSCLC, consistent with findings from the ASTRUM-004 trial. The long-term survival benefit warrants further validation with extended follow-up.

OBJECTIVE:This study aimed to create and validate a machine learning (ML) model to predict the likelihood of invasive mechanical ventilation (IMV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated by respiratory failure. METHODS:Data from patients diagnosed with AECOPD and respiratory failure were retrospectively extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV). A total of 551 cases were split 7:3 into a training set (385 cases) for model construction and an internal validation set (166 cases). The IMV served as the outcome event. Features were selected with the Boruta algorithm and least absolute shrinkage and selection operator (LASSO). Eight ML algorithms-XGBoost, decision tree (DT), random forest (RF), support-vector machine (SVM), LightGBM, CatBoost, Gaussian naïve Bayes (NB) and K-nearest neighbor (NN)-were trained with 10-fold cross-validation. Model performance was assessed by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, F1 score, calibration curve, decision curve and clinical impact curve. An external validation cohort of 100 AECOPD-respiratory failure patients admitted to Baoying People's Hospital between January 2020 and August 2025 was collected. The final best model was interpreted with SHapley Additive exPlanations (SHAP) to clarify feature importance and decision logic, and an interactive dynamic nomogram was plotted to increase readability. RESULTS:Boruta plus LASSO identified total calcium, partial pressure of oxygen (PO2), oxygen saturation (SpO2) and sepsis as significant predictors. XGBoost outperformed the other algorithms, achieving an internal validation accuracy of 72.2%, sensitivity of 64.6%, specificity of 79.8 %, F1 score of 69.7% and AUC of 0.813 (95% CI 0.748-0.878). The external validation accuracy reached 76.4%, the sensitivity reached 82.6%, the specificity reached 70.0%, the F1 score reached 78.7%, and the AUC reached 0.840 (95% CI 0.801-0.879). SHAP analysis further indicated that PO2 and SpO2 were the primary drivers of model decisions. An interactive dynamic nomogram was successfully constructed. CONCLUSION:IMV in AECOPD patients with respiratory failure was associated with total calcium, PO2, and SpO2 levels and sepsis. The developed XGBoost model demonstrated good predictive value for IMV in this clinical population.

e18078 Background: In recent years, endoscopic surgery has become the first-line treatment for surgically resectable recurrent nasopharyngeal carcinoma (rNPC); however, the role of programmed death 1 (PD-1) blockade in patients after endoscopic surgery for rNPC remains unknown. This study aimed to evaluate the efficacy and safety of tislelizumab as adjuvant consolidation therapy. Methods: This was a single-center, open-label, randomized, controlled, phase 2 trial. Eligible patients aged 18–70 years were histopathologically diagnosed with undifferentiated or differentiated nonkeratinizing rNPC. Patients with rNPC were randomized to receive endoscopic surgery alone or endoscopic surgery followed by tislelizumab treatment. Tislelizumab was administered as a 200 mg intravenous infusion every 3 weeks until disease progression or unacceptable toxicity was confirmed. The primary endpoint was progression-free survival (PFS) at 1 year, and secondary endpoints included 1-year progression-free interval (PFI), 1-year overall survival (OS), and safety. Results: The trial is ongoing. Forty-two patients had been enrolled between November 23, 2021 and May 8, 2024. At a median follow-up of 18 months (IQR 10–27), the 1-year PFS was significantly higher in the tislelizumab group (94%, 95% confidence interval (CI) 83–100%) than in the endoscopic surgery alone group (57%, 95% CI 38–85%). The 1-year PFI was also higher in the tislelizumab group (100%, 95% CI: 100%–100%) than in the endoscopic surgery alone group (60%, 95% CI: 40%–89%). No significant difference in the 1-year OS was observed at the data cutoff. Common surgery-related adverse events in the endoscopic surgery group included skull base osteonecrosis (30%), with three cases of grade 2 and three cases of grade 3 or higher AEs. In the tislelizumab group, 18% of patients with osteonecrosis only experienced grade 1 AEs. Grade ≥3 immune-related adverse events (irAEs) occurred in 9% of tislelizumab recipients, and the most common irAEs in this group were hypothyroidism, affecting 27%, and pruritus, observed in 9%. Conclusions: Tislelizumab as adjuvant therapy significantly enhanced PFS and PFI, with a favorable safety profile. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with resectable rNPC following endoscopic surgery. Clinical trial information: NCT05092217 .

This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC. Locally advanced hypopharyngeal squamous cell carcinoma is an aggressive form of head and neck cancer with a poor prognosis. Here, the authors report the safety and efficacy of induction camrelizumab (anti-PD-1) and chemotherapy for the treatment of locally advanced hypopharyngeal squamous cell carcinoma.

Background Previous studies have investigated the value of induction chemotherapy (IC) in organ preservation strategies for head and neck cancers. This study evaluated the effectiveness of sequential IC with radiotherapy as a laryngeal preservation strategy for locally advanced hypopharyngeal carcinoma (LAHSCC). Methods One hundred and forty-two consecutive patients with LAHSCC were retrospectively analyzed who received three IC regimens from 2015 to 2019. Results In the TP (docetaxel plus cisplatin), TPF (TP plus 5-fluorouracil), and TPX (TP plus capecitabine) IC groups, there were 51, 29, and 62 patients, respectively. The primary tumor objective response rates were 51%, 55.2%, and 71%, and the 3-year survival rates with preserved larynx were 36.6%, 31.8%, and 51.2%, respectively (p = 0.03). There was no difference in overall survival and the adverse events were tolerable. Conclusions The TPX regimen displayed good efficacy and safety, indicating its potential as a therapeutic IC regimen for LAHSCC.

Abstract Extranodal natural killer/T‐cell lymphoma (ENKL), nasal‐type is a rare but highly aggressive disease with poor prognosis. Optimal treatment strategies for newly diagnosed localized ENKL have not been fully defined. Here we retrospectively analyzed 72 patients with newly diagnosed stage IE/IIE ENKL treated with gemcitabine, dexamethasone, and cisplatin (GDP) regimen chemotherapy with sandwiched radiotherapy in our department between May 2012 and September 2014. After 2 cycles of GDP induction chemotherapy, the complete response rate (CRR) and overall response rate (ORR) were 30.6% (22/72) and 91.7% (66/72). After whole treatment completion, the CRR and ORR were 81.9% (59/72) and 91.7% (66/72), respectively. With a median follow‐up of 57.8 months (Interquartile Range 54.0‐64.5 months), the 5‐year progression‐free survival rate was 70.9% (95% CI, 60.1% to 81.7%), and the 5‐year overall survival rate was 72.0% (95% CI, 61.6% to 82.4%), respectively. Patients with CRR after treatment had better prognosis than their counterparts. The major adverse events were myelosuppression, liver dysfunction, gemcitabine‐related skin rash, and digestive tract toxicities. Grade 3 to 4 neutropenia and thrombocytopenia were 18.0% (13/72) and 15.3% (11/72), respectively. No treatment related deaths were observed. It is concluded that the GDP regimen with sandwiched radiotherapy was an effective and well‐tolerated treatment for newly diagnosed stage IE/IIE ENKL, nasal‐type.

Background: Most previous studies are separate dosimetric analyses of conductive or sensorineural hearing loss, and they are not conducive to a comprehensive assessment of auditory radiation damage. Aims/objectives: Our study aimed to evaluate the long-term incidence of sensorineural hearing loss (SNHL) or conductive hearing loss (CHL) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiation therapy (IMRT), and to investigate the relationship between SNHL or CHL and patient factors, treatment-related factors, and radiation dose parameters. Material and methods: Seventy patients (117 ears) with NPC, who were also treated with IMRT in our hospital from 2006 to 2014, were retrospectively analyzed. Radiation doses to the Eustachian tube (ET), middle ear (ME), cochlear (Co), and internal auditory canal (IAC) were assessed. Pure tone audiometry and impedance audiometry were performed before and during the follow-up period. The relationships between low-frequencies (0.5-2 kHz) or high-frequency (4 kHz) SNHL/CHL and radiotherapy dose parameters were analyzed. Results: Of the 117 ears studied, 7.69% had low-frequency SNHL, 35.9% had high-frequency SNHL, 23.93% had low-frequency CHL, and 18.80% had high-frequency CHL. The incidence of high-frequency CHL was higher in the T4 group than in the T (1-3) group (p < .05). When IAC D-max > 42.13 Gy or IAC D-mean > 32.71 Gy, the risk of high-frequency SNHL increased in NPC patients. When ME D-max > 44.27 Gy, ME D-mean > 29.28 Gy, or ET D-max > 57.23 Gy, the risk of high-frequency CHL in NPC patients increased. Conclusions and significance: SNHL and CHL remain common ear complications after IMRT for NPC. IAC D-max, IAC D-mean, ME D-max,D- ME D-mean, and ET D-max all need to be carefully considered during the IMRT treatment protocol.

Objective To investigate the clinical features and treatment strategies of primary diffuse large B cell lymphoma (DLBCL) of nasal cavity and paranasal sinuses.Methods The clinical features and prognostic factors of 30 patients who were newly diagnosed as primary DLBCL of nasal cavity and paranasal sinuses from January 2007 to December 2014 were retrospectively analyzed.Results Among 30 patients,21 cases were male and 9 were female;the median age was 63 years;26 patients were Ann Arbor stage Ⅰ,4 patients were stage Ⅱ,none presented with B symptoms.All patients received chemotherapy and radiotherapy;8 patients received R-CHOP and 22 patients received CHOP-like-based chemotherapy regimens with a median of 4 cycles.Patients were treated with three-dimensional conformal radiotherapy with a dose of 36 ～54 Gy(median dose of 46.8 Gy).One patient received central nervous system(CNS) prophylaxis during the treatment.There were 22 patients in complete remission,6 in partial remission,one in progressive disease,and one died of upper gastrointestinal hemorrhage during radiotherapy.With a median follow-up of 72 months,the 5-year survival rate was 56.7％ (95％ CI:47.7％ to 65.7％) and two CNS relapses occurred.Conclusions Patients with primary DLBCL of nasal cavity and paranasal sinuses commonly present with localized disease but have a poor prognosis.At present,R-CHOP chemotherapy regimen is mainly used for the treatment of the disease and local radiotherapy also has an important role.CNS prophylaxis should not be routinely used in these patients.

7561 Background: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type is highly aggressive with rather poor prognosis. Combined chemoradiotherapy is necessary for those having fever and/or extensive lesions. It is imperative to develop an effective chemotherapy regimen as ENKTL is often refractory to CHOP. This study was conducted to evaluate the efficacy and safety profiles of gemcitabine, dexamethasone, and cisplatin (GDP) as initial treatment combined with radiotherapy for patients with stage IE/IIE ENKTL. Methods: This study was conducted of

Background: Cancer-related systemic inflammation has been demonstrated to be associated with poor outcome in multiple types of cancers. Meanwhile, the local inflammation, which is characterized by dense intratumoral immune infiltrate, is a favorable predictor of survival outcome.Purpose: To evaluate the role of systemic and local inflammation in predicting outcome in patients with laryngeal squamous cell carcinoma.Patients and methods: In this retrospective study, 120 patients who had undergone postoperative radiotherapy were enrolled. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to- lymphocyte ratio (PLR), as calculated from pretreatment whole blood counts, were used to indicate systemic inflammation. The optimal cutoff values of NLR and PLR were determined using receiver operating characteristic curve analysis. Tumor infiltrating lymphocytes (TILs) density, as assessed by pathologist review of hematoxylin and eosin-stained slides, was used to represent local inflammation. Overall survival (OS) and recurrence-free survival (RFS) were assessed using the Kaplan-Meier method and multivariate Cox regression analysis.Results: The best cutoff was 2.79 for NLR and 112 for PLR. Kaplan-Meier analysis revealed that high NLR, high PLR, and low TILs density were significantly correlated with inferior OS and RFS, respectively (all P<0.05). The Cox proportional multivariate hazard model showed that a high pretreatment PLR and a low TILs density were both independently correlated with poor OS and RFS, respectively (all P<0.05).Conclusion: Markers of systemic and local inflammation, especially PLR and TILs density, are reliable prognostic factors in patients with laryngeal squamous cell carcinoma.

Objective To identify the expression of transcription factor Sp1 in NK/T-cell lymphoma (NK/TCL) cell lines and to investigate the role of Sp1 in regulation of cell invasion. Methods Real-time PCR, immunofluorescence and Western blot were performed to detect the expression of Sp1 in NK/TCL cell lines SNK-1 and SNK-6 and normal NK cells. Expression levels of IGF-1R and MMP-2 were measured by real-time PCR and Western blot, respectively. Transwell assay was applied to observe the effects of mythramycin A(MIT) on cell invasion. Results Sp1 expression in mRNA and protein were over-expression in NK/TCL cell lines SNK-1 and SNK-6 when compared with normal NK cells. Inhibition of Sp1 by MIT remarkably reduced expression of IGF-1R and MMP-2 in SNK-1, SNK-6 and as a result, or significantly suppressed cell invasion. Expression levels of Sp1 mRNA in SNK-1 and SNK-6 were (9.4±0.3) and (10.6±0.3) foldsincrease as compared with that of control group, respectively (P=0.005 2, P=0.003 7). Levels of Sp1 protein were (5.4±0.3) and (8.6±0.5) foldsincrease times than control groups, respectively (P=0.008 3, P=0.006 9). Inhibition of Sp1 by MIT (100 nmol/L) remarkably reduced expression levels of IGF-1R mRNA by (83.9±3.7) % and (65.8±4.2) % (P = 0.008 2, P = 0.009 7) as compared with controls. Meanwhile, levels of IGF-1R protein were reduced by (51.5±7.1) % and (49.6±9.1) % (P = 0.017 8, P = 0.015 5) as compared with control group. Inhibition of Sp1 by MIT (100 nmol/L) significantly reduced cell invasion and MMP-2 expression in the two cell lines,the cell invasion rates were reduced by (29.6±6.4) % and (37.2±7.6) % (P =0.041 8, P = 0.037 2) in SNK-1 and SNK-6 as compared with control group. The MMP-2 protein levels were found to be (52.7±4.7) % and (29.7±5.6) % (P = 0.028 6, P = 0.020 2) of control group. Conclusion Sp1 is over-expressed in NK/TCL cell lines, and it promotes NK/TCL cell invasion by up-regulating IGF-1R and further increasing MMP-2 expression.

As one of the common malignant tumors that threaten human health severely, gastric carcinoma is the second highest cause of cancer death and the fourth most common cancer globally. However, the mechanism underlying gastric cancer is still not fully understood. PABPC1 plays an important role in translation, control the rate of mRNA deadenylation and participates in mRNA decay, which is involved in carcinogenesis. Here in present study, we reported that PABPC1 is an oncogenic protein in gastric carcinoma. The results showed that PABPC1 is upregulated in gastric carcinoma tissues, and high PABPC1 expression predicts poor survival. PABPC1 regulates proliferation and transformation of gastric cancer cells in vitro and in vivo. PABPC1 knockdown induces apoptosis by upregulating pro-apoptotic proteins and downregulating anti-apoptotic proteins. In addition, miR-34c is a target of PABPC1, and miR-34c is critically essential for the function of PABPC1. In summary, PABPC1 exerts carcinogenesis and promotes growth and survival of gastric cancer cells by regulating miR-34c.

Zhu Chen, Sai-Juan Chen, Wei-Li Zhao and colleagues identify recurrent loss-of-function mutations in the RNA helicase gene DDX3X in 20% of subjects with natural killer/T-cell lymphoma (NKTCL) in their study. The results suggest that DDX3X acts as a tumor suppressor and that its inactivation leads to poor clinical outcome.