The gastrointestinal (GI) tract is one of the most common extranasal sites in extranodal NK/T-cell lymphoma (ENKTL). However, data regarding ENKTL involving the GI tract are relatively scarce. Thus, we performed a multicenter, multinational retrospective study to analyze clinical features and treatment outcomes of ENKTL involving the GI tract. Patients with ENKTL involving the GI tract diagnosed in twelve participating centers between 1991 and 2012 were retrospectively analyzed from five Asian countries. The analysis of 81 patients with ENKTL involving the GI tract revealed that more than 60% of patients presented as advanced disease with B symptoms. 55 patients (68%) had GI manifestations including abdominal pain (n = 26, 32%), GI tract bleeding (n = 17, 21%) and bowel perforation (n = 12, 15%). The most common GI site was the small intestine, including the jejunum and ileum (n = 57, 70.3%). There were 34 patients (42%) who received systemic chemotherapy while 33 patients (41%) underwent surgery plus chemotherapy. However, 35 patients (43%) died due to disease progression, and treatment-related mortality including sepsis occurred in 17 patients (21%). Thus, the median overall survival was 7.8 months (95% Confidence interval: 3.9 – 11.7 months). Patients who could undergo surgery plus chemotherapy showed a trend of better survival than those treated with chemotherapy alone. Overall, the data indicated that ENKTL involving the GI tract has a dismal prognosis despite active treatment including chemotherapy and surgery. Thus, more effective treatment strategies are required for this disease entity.

Although the incidence of glioma is relatively low, it is the most malignant tumor of the central nervous system. The prognosis of high-grade glioma patient is very poor due to the difficulties in complete resection and resistance to radio-/chemotherapy. Therefore, it is worth investigating the molecular mechanisms involved in glioma drug resistance. MicroRNAs have been found to play important roles in tumor progression and drug resistance. Our previous work showed that miR-181b is involved in the regulation of temozolomide resistance. In the current study, we investigated whether miR-181b also plays a role in antagonizing the effect of teniposide. MiR-181b expression was measured in 90 glioma patient tissues and its relationship to prognosis of these patients was analyzed. Cell sensitivity to teniposide was tested in 48 primary cultured glioma samples. Then miR-181b stably overexpressed U87 cells were generated. The candidate genes of miR-181b from our previous study were reanalyzed, and the interaction between miR-181b and target gene MDM2 was confirmed by dual luciferase assay. Cell sensitivity to teniposide was detected on miR-181b over expressed and MDM2 down regulated cells. Our data confirmed the low expression levels of miR-181b in high-grade glioma tissues, which is related to teniposide resistance in primary cultured glioma cells. Overexpression of miR-181b increased glioma cell sensitivity to teniposide. Through target gene prediction, we found that MDM2 is a candidate target of miR-181b. MDM2 knockdown mimicked the sensitization effect of miR-181b. Further study revealed that miR-181b binds to the 3’-UTR region of MDM2 leading to the decrease in MDM2 levels and subsequent increase in teniposide sensitivity. Partial restoration of MDM2 attenuated the sensitivity enhancement by miR-181b. MiR-181b is an important positive regulator on glioma cell sensitivity to teniposide. It confers glioma cell sensitivity to teniposide through binding to the 3’-UTR region of MDM2 leading to its reduced expression. Our findings not only reveal the novel mechanism involved in teniposide resistance, but also shed light on the optimization of glioma treatment in the future.

Context: Precision medicine for pituitary neuroendocrine tumors (PitNETs) is limited by the lack of reliable research models. Objective: To generate patient-derived organoids (PDOs), which could serve as a platform for personalized drug screening for PitNET patients. Design: From July 2019 to May 2022, a total of 32 human PitNET specimens were collected for the establishment of organoids with an optimized culture protocol. Setting: This study was conducted at Sun Yat-Sen University Cancer Center. Patients: PitNET patients who were pathologically confirmed were enrolled in this study. Interventions: Histological staining and whole-exome sequencing were utilized to confirm the pathologic and genomic features of PDOs. A drug response assay on PDOs was also performed. Main Outcome Measures: PDOs retained key genetic and morphological features of their parental tumors. Results: PDOs were successfully established from various types of PitNET samples with an overall success rate of 87.5%. Clinical nonfunctioning PitNETs-derived organoids (22/23, 95.7%) showed a higher likelihood of successful generation compared to those from functioning PitNETs (6/9, 66.7%). Preservation of cellular structure, subtype-specific neuroendocrine profiles, mutational features, and tumor microenvironment heterogeneity from parental tumors was observed. A distinctive response profile in drug tests was observed among the organoids from patients with different subtypes of PitNETs. With the validation of key characteristics from parental tumors in histological, genomic, and microenvironment heterogeneity consistency assays, we demonstrated the predictive value of the PDOs in testing individual drugs. Conclusion: The established PDOs, retaining typical features of parental tumors, indicate a translational significance in innovating personalized treatment for refractory PitNETs.

Background: Brain metastases (BM) from non-small-cell lung cancer (NSCLC) is the most common brain malignancy. Systemic inflammation biomarkers have recently been evaluated as prognosis indicators in several tumors. The combination of these markers has not been evaluated in NSCLC with BM yet. Here, we explored the predictive value of pretreatment inflammatory biomarkers and established a novel, clinically applicable prognostic index for NSCLC patients with BM. Methods: A retrospective investigation of 951 NSCLC patients newly diagnosed with BM at Sun Yat-sen University Cancer Center was conducted. We randomly divided patients into a training cohort (n = 674) or validation cohort (n = 277). Receiver operating characteristic (ROC) curve analysis was carried out to obtain the optimal cut-off values of pretreatment systemic inflammatory indexes. The associations between serum biomarkers and overall survival (OS) were analyzed by Kaplan–Meier curves and Cox proportional models. The resulting prediction model has been externally verified through the validation cohort. Results: The optimal cut-off value of the neutrophil–lymphocyte ratio (NLR) in predicting OS was 4.71, while the clinical standard of 40 mg/L was chosen as the optimal cut-off value of albumin. Univariate and multivariate analyses revealed that patients receiving local treatment, chemotherapy, a NLR < 4.71 and albumin ≥ 40 mg/l independently predicted improved survival. We combined the two inflammatory indexes (NLR and albumin level) to establish the modified systemic inflammation score (mSIS) which divides patients into low risk, medium risk or high-risk groups. The 1-year OS rates of three groups were 59.7%, 40.5% and 29.4%, respectively in the training cohort. The same result was verified in the validation cohort with the 1-year OS rates 69.7%, 47.0% and 7.7%, respectively. The mSIS exhibited better discrimination power than the American Joint Committee on Cancer’s (AJCC) 7th T + N staging system in the training cohort (Harrell’s concordance index (C-index): 0.744 vs 0.502, P < 0.05), and the discrimination was also superior to that of AJCC’s 7th T + N staging system in the validation cohort (C-index: 0.724 vs 0.527, P < 0.05). The 1-year and 2-year OS rates of the AUC also exhibited superior survival predictive ability to that of the AJCC’s 7th T + N staging system in NSCLC patients with BM. Conclusion: The pretreatment mSIS may be an independent prognostic factor for OS in NSCLC patients with BM and warrants further research.

A photocurable hydrogel showed potential application prospects in patient-derived glioblastoma organoid cultures.