[Clinical analyses of 24 patients with primary pulmonary NK/T-cell lymphoma].

Objective: To explore the clinical characteristics, the best treatment and prognostic factors of primary pulmonary NK/T-cell lymphoma. Methods: A total of 24 cases with primary pulmonary NK/T-cell lymphoma from April 2011 to May 2019 were analyzed retrospectively. Survival analysis was performed using the Kaplan-Meier method and groups were compared using the log-rank test. Multivariate analysis using Cox proportional hazard regression model was conducted to confirm independent prognostic factors for overall survival (OS) and progression-free survival (PFS) . Results: ①The cohort of 24 patients included 16 male and 8 female with a median age of 49 years (range, 4-76 years) old. ②Most patients initially presented with a fever (66.7%) , cough and dyspnea. Chest imaging manifestations were primarily unilateral (45.8%) or bilateral (54.2%) pulmonary consolidation, nodules or mass. ③20 patients received chemotherapy, radiotherapy or hematopoietic stem cell transplantation, the rest 4 cases palliative treatment. Median OS was 9.5 months (range, 0.1-26.0 months) . The estimated 1-year OS rate was 45.8%. Overall response rate of patients treated with asparaginase-based regimen was 88.2%. ④In univariate survival analysis, age≤60 was prognostic for longer OS and PFS, compared with age>60 (P=0.002 and 0.004, respectively) ; ECOG≤2 was prognostic for longer OS and PFS, compared with ECOG>2 (P=0.042 and 0.004, respectively) . In multivariate survival analysis, age>60 and ECOG>2 were significantly correlated with inferior OS and PFS (OS: P=0.024 and 0.024, respectively; PFS: P=0.035 and 0.024, respectively) . Conclusions: Primary pulmonary NK/T-cell lymphoma was a rare disease with poor prognosis. Asparaginase-based regimens appeared to be effective. Age and ECOG served as independent prognostic factors for primary pulmonary NK/T-cell lymphoma patients.

[14-3-3ζ protein mediates gemcitabine resistance in NK/T-cell lymphoma].

Objective: To explore the molecular mechanisms of 14-3-3ζ in gemcitabine resistance in extranodal NK/T-cell lymphoma, nasal type (ENKTL) . Methods: The effects of cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and transwell assay. YTS cells were exposed to gradually increased concentrations of gemcitabine to establish gemcitabine-resistant YTS cells (YTS-gem) in vitro. 14-3-3ζ specific siRNA lentiviral vector was transfected into YTS and YTS-gem cells to downregulate 14-3-3ζ expression, and stable transfected cell clones were screened. The protein expression was determined by Western blot. Results: ①14-3-3ζ expression was significantly up-regulated in gemcitabine resistant YTS-gem cells, comparing with that of YTS cells (P<0.05) . ②The results of CCK-8 and transwell assay showed that downregulation of 14-3-3ζ significantly reduced the cell proliferation and invasion abilities (P<0.05) . ③Downregulation of 14-3-3ζ could restore gemcitabine sensitivity in gemcitabine resistant YTS-gem cells (P<0.05) . ④Western blotting results showed that knockdown of 14-3-3ζ significantly upregulated pro-apoptotic Bax, and downregulated anti-apoptotic Bcl-2, Caspase-3, cleaved caspase-3, Cyclin D1 in gemcitabine-resistant YTS-gem cells (P<0.05) . There was no significant difference in p53 ang P-gp expression levels. Conclusions: 14-3-3ζ was upregulated in gemcitabine resistant YTS cells. Overexpression of 14-3-3ζ promoted cell proliferation and enhanced cell migration. 14-3-3ζ contributed to gemcitabine resistance to ENKTL through anti-apoptosis.

[Clinical characteristics of lung NK/T cell lymphoma misdiagnosed as pneumonia].

Objective: To investigate the clinical features of lung natural killer (NK)/T cell lymphoma. Methods: The clinical data of patients with lung NK/T-cell lymphoma confirmed by pathology who were hospitalized due to lung shadow and initially treated as pneumonia from the First Affiliated Hospital of Zhengzhou University was collected from June 2013 to January 2019. The clinical manifestations, laboratory tests, chest CT findings, treatment procedures, outcomes, and misdiagnosis were retrospectively analyzed. Results: Among the 15 enrolled patients with lung NK/T-cell lymphoma, 5 were primary and the other 10 were secondary. There were 8 males and 7 females, aged 20-76 years. Fever presented in 14 cases, dyspnea was observed in 4 cases and 2 cases had cough. A total of 12 cases had leukopenia, 10 cases had mononuclear cell increase, 10 cases had liver dysfunction, 13 cases had elevated serum lactate dehydrogenase (LDH), and 2 cases of primary lung NK/T-cell lymphoma had increased pleural LDH and adenosine deaminase. Five cases of primary lung NK/T-cell lymphoma had multiple lung lesions, with diffuse multiple solid shadows, ground glass and patchy shadows, some with nodules; 10 cases of secondary lung NK/T-cell lymphoma showed nodular masses, some were accompanied by patchy shadows, and most patients had multiple lesions scattering in the lung. All the fifteen patients were misdiagnosed as pneumonia in the early stage, and then were diagnosed by percutaneous lung biopsy or transbronchial biopsy. Six patients underwent chemotherapy, of which 1 achieved complete response, 4 were in follow-up and 1 died of respiratory failure; 5 patients died of respiratory failure after diagnosis and 4 patients discharged and died within half a year. Conclusions: The lung NK/T-cell lymphoma are rare. The clinical manifestations and pulmonary imaging findings are indistinguishable from pulmonary inflammatory lesions. They are easily misdiagnosed as pneumonia. Early CT-guided percutaneous lung biopsy or transbronchial biopsy can improve the diagnostic accuracy.

[PD-L1 expression is related with prognosis of small cell lung cancer].

Objective: To explore the correlation between programmed death ligand 1 (PD-L1) expression and clinicopathological features and prognosis of small cell lung cancer (SCLC). Methods: The clinicopathological data of 64 patients with small cell lung cancer from January 2013 to December 2016 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed in this study. The correlation between PD-L1 expression and the clinicopathological features and prognosis of SCLC was analyzed. Results: Immunohistochemical staining revealed that PD-L1 expression was observed in 60.9% (39/64) of patients with small cell lung cancer. PD-L1 expression was significantly related to stages (P<0.001). Univariate analysis showed that the median overall survival of PD-L1 negative group was longer than PD-L1 positive group (16 months vs 14 months, P<0.001). Median progression-free survival of PD-L1 negative group was longer than PD-L1 positive group(15 months vs 9 months, P<0.000 1). In multivariate analysis, PD-L1 positive was significantly correlated with inferior progression-free survival (P=0.006). Conclusions: PD-L1 expression rate was high in small cell lung cancer. PD-L1 expression was an independent predictor for poor prognosis of patients with small cell lung cancer.

Opa interacting protein 5 promotes metastasis of nasopharyngeal carcinoma cells by promoting EMT via modulation of JAK2/STAT3 signal.

OBJECTIVE: Opa interacting protein 5 (OIP5), as a tumor promoter gene, has emerged as a regulator in several types of tumors. However, the role of OIP5 in nasopharyngeal carcinoma (NPC) has not been reported. In this study, we aimed to explore the expression and biological function of OIP5 in NPC. PATIENTS AND METHODS: The lung cancer datasets GSE12452 and GSE53819 were downloaded from the Gene Expression Omnibus (GEO) repository. Real-time-Polymerase Chain Reaction (RT-PCR) was performed to detect the expression levels of OIP5 mRNA. Cell Counting Kit-8 (CCK-8), colony-formation assay, wound healing assay and transwell assay were conducted to measure cells' proliferation, migration and invasion. Flow cytometry was used for analysis of apoptosis. Western blot assays were used to assess the effects of OIP5 on EMT and JAK2/STAT3 pathway. RESULTS: The up-regulation of OIP5 mRNA was observed in NPC tissues from both GSE12452 and GSE53819. The results of RT-PCR also showed that the expression of OIP5 mRNA was significantly up-regulated in several NPC cell lines compared to normal nasopharyngeal cells. Furthermore, lost-function assay revealed that the knockdown of OIP5 markedly suppressed NPC cells proliferation, migration and invasion, and promoted cell apoptosis. In addition, the results of Western blot showed that silencing of OIP5 suppressed the EMT in NPC cell line. Meanwhile, the knockdown of OIP5 remarkably decreased the expression of p-JAK2 and p-STAT3 protein in both CNE1 and SUNE1 cells. CONCLUSIONS: Our data indicated that OIP5 was highly expressed in NPC and promoted NPC progression by modulating JAK2/STAT3; our results shed light on utilizing OIP5 as a potential novel therapeutic target for the treatment of NPC.

Efficacy of a pegaspargase-based regimen in the treatment of newly-diagnosed extranodal natural killer/T-cell lymphoma.

Extranodal natural killer (NK)/T-cell lymphoma (ENKL) is an aggressive neoplasm with poor prognosis. Currently, there is no consensus on the optimal treatment of this disease. In this study, we report the efficacy of a pegaspargase (PEG-Asp)-based chemotherapy, a DDGP regimen (PEG-Asp, dexamethasone, cisplatin, gemcitabine), for the treatment of newly-diagnosed ENKL. From August 2010 to May 2012, 12 patients with newly-diagnosed stage II - IV ENKL were initially treated with a DDGP regimen in our center. Ten patients (10/12, 83.3%) achieved complete response (CR) and two (2/12, 16.7%) achieved partial response (PR). The objective overall response rate (ORR) was 100%. Three patients (3/12, 25.0%) relapsed, and as a result, two died of disease. Eight patients (8/12, 66.7%) were alive with no evidence of disease (NOD) after a median follow-up of 19 months (range 16 - 31 months). Hematologic toxicity was the most frequent toxicity reported in this study. Grade 3/4 leukopenia and neutropenia were common and both occurred in eight patients (8/12, 66.7%), respectively. Additionally, six patients (6/12, 50.0%) experienced grade 3/4 thrombocytopenia and three (3/12, 25.0%) experienced grade 3/4 anemia. However, no patient died of hematologic toxicity. Our results demonstrate the significant efficacy and safety profile of a DDGP regimen in the treatment of newly-diagnosed ENKL, and indicate the potential of this regimen as a first-line therapy against this disease.