Clinical features, prognostic stratification, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma: a multi-institutional real-world study.

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.

Tislelizumab and radiation therapy in low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type: a phase II study protocol.

Low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type has a favorable outcome with radiation therapy alone, and the addition of chemotherapy shows no survival benefit. Nonetheless, a proportion of patients will relapse or progress, with a dismal outcome, highlighting the need for a novel therapeutic strategy. Promising preliminary findings indicate the efficacy of PD-1/PD-L1 inhibitors in extranodal natural killer/T-cell lymphoma, nasal type, with good toxicity profiles. Here we describe the design of a phase II study (CLCG-NKT-2101), which is evaluating the safety and efficacy of adding anti-PD-1 antibody to the current radiation therapy regimen in low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type patients. Tislelizumab will be added in an inductive and concurrent way to radiation therapy. The primary end point will be the complete response rate after induction immunotherapy. Clinical trial registration: ClinicalTrials.gov (NCT05149170).

Intensive therapy can improve long-term survival in newly diagnosed, advanced-stage extranodal NK/T-cell lymphoma: A multi-institutional, real-world study.

The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT.

Extranodal natural killer/T-cell lymphoma with hepatosplenic involvement: a retrospective study of a consecutive 14-year case series.

Extranodal natural killer/T-cell lymphoma (ENKTL) with hepatosplenic involvement is rare, accounting for approximately 0.2% of ENKTL cases. The clinicopathologic features of ENKTL with hepatosplenic involvement are still poorly understood. Seven cases of ENKTL with hepatosplenic involvement were investigated retrospectively by clinical features, pathology, immunophenotype, genotype, Epstein-Barr virus (EBV) status, and survival analysis. The median age was 36 years; three patients (3/7) had a history of primary nasal ENKTL. Six cases (6/7) presented liver or spleen structures that were replaced by neoplasms, and the neoplastic cells displayed diffuse infiltration; one case (1/7) displayed neoplastic cells scattered in hepatic sinuses and portal areas. The cellular morphology and immunohistochemical features were similar to those of ENKTL involving other sites. Follow-up data were available in five of the seven patients. All five patients received first-line chemotherapy based on L-asparaginase. Three patients died, and two were still alive by the last follow-up. The median overall survival (OS) was 21 months. ENKTL with hepatosplenic involvement is rare, regardless of whether it is initial or secondary. There are two histopathologic patterns of ENKTL with hepatosplenic involvement, and L-asparaginase-based chemotherapy combined with AHSCT might yield good efficacy. Morphological features of ENKTL in the spleen and liver A The architecture of the spleen was affected, and dense infiltration of the neoplastic cells was observed in the left part; B Focal infiltration of the neoplastic cells was located in the red pulp; C Dense infiltration of the neoplastic cells in the liver, accompanied by fatty change of hepatocytes and congestion; D More neoplastic cells accumulated in sinusoidal region.

Prognostic value and computer image analysis of p53 in mantle cell lymphoma.

P53 prognostic cut-off values differ between studies of mantle cell lymphoma (MCL), and its immunohistochemistry (IHC) interpretation is still based on semiquantitative estimation, which might be inaccurate. This study aimed to investigate the optimal cut-off value for p53 in predicting prognosis of patients with MCL and the possible use of computer image analysis to identify the positive rate of p53. We calculated p53 positive rate using QuPath software and compared it with the data obtained by manual counting and semiquantitative estimation. Survival curves were generated by using the Youden index and the Kaplan-Meier method. The chi-squared (χ2) test was used to compare MIPI, Ann Arbor stage, and cell morphology with p53. Spearman rank correlation test and Bland-Altman analysis were used to compare manual counting, computer image analysis and semiquantitative estimation, as well as the consistency between different observers. The optimal cut-off value of p53 for predicting prognosis was 20% in MCL patients. Patients with p53 ≥ 20% had a significantly worse overall survival (OS) than those with p53 < 20% (P < 0.0001). MCL patients with MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant cell morphology had more p53 ≥ 20%. There was a strong correlation between computer image analysis and manual counting of p53 from the same areas in MCL tissues (Spearman's rho = 0.966, P < 0.0001). The results of computer analysis are completely consistent between observers, and computer image analysis of Ki-67 can predict the prognosis of MCL patients. MCL patients with p53 ≥ 20% had a shorter OS and a tendency for MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant. Computer image analysis could determine the actual positive rate of p53 and Ki-67 and is a more attractive alternative than semiquantitative estimation in MCL.

Comparative Study of the Clinical Pathology, Immunophenotype, Epstein-Barr Virus Infection Status, and Gene Rearrangements in Adult and Child Patients With Hydroa Vacciniforme-Like Lymphoproliferative Disorder.

BACKGROUND: Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a rare Epstein-Barr virus (EBV)-associated lymphoma that mainly affects children. OBJECTIVES: To examine the similarities and differences in the clinical pathological features, EBV infection status, and gene rearrangements in adults and children patients with HVLPD. METHODS: We compared the clinical manifestations, histopathology, immunophenotypical features, EBV infection status, and T-cell receptor gene rearrangements in the adult and children HVLPD groups. RESULTS: Clinical manifestations differed between children and adults groups. The children were characterized by blisters and severe facial swelling, whereas the adults were characterized by mild facial swelling and papules. Mosquito bite was significantly related to morbidity in the children group. Histologically, the number of mast cells in the adult group was greater than in the children group (P < 0.05). There were no significant differences in EBV infection status or TCR-γ gene rearrangements between 2 groups. CONCLUSIONS: There were differences in clinical pathology and prognosis between the 2 groups. A higher mast cell count and T-cell phenotype might be associated with a poor prognosis.

Incidence, clinical characteristics, and outcome of interstitial pneumonia in patients with lymphoma.

Interstitial pneumonia (IP) is a lethal complication in lymphoma patients undergoing chemotherapy. A total of 2212 consecutive patients diagnosed with lymphoma between 2009 and 2014 were enrolled in the present study. IP was defined as diffuse pulmonary interstitial infiltrate found on computed tomography scans. IP was observed in 106 patients. Of these, 23 patients were excluded from the study. Finally, 83 patients with IP were included in this study. The incidence of IP was 3.9% (7/287) in Hodgkin lymphoma and 2.4% (76/1925) in non-Hodgkin lymphoma (P = 0.210). The median number of chemotherapy cycles before IP was 3. The median time from the cessation of chemotherapy to IP was 17 days. Eighty-two (98.8%) patients recovered after the treatment with glucocorticoids. Sixty-six (79.5%) patients had a delay in chemotherapy, and 14 (16.9%) patients had premature termination of chemotherapy. Sixty-nine patients were re-treated with chemotherapy after remission from IP, of which 22 (31.9%) experienced IP recurrence. The incidence of IP recurrence was significantly higher in patients re-treated with a similar regimen than in those re-treated with an alternative regimen (65.4 vs. 11.6%, P < 0.001). In a multivariate Cox regression analysis, B symptoms and a history of drug allergies were identified as risk factors for IP. In conclusion, IP is a life-threatening complication in lymphoma patients. Glucocorticoid therapy with continuous monitoring of chest radiographic changes may be a favourable strategy for treating IP. However, IP may recur, especially in patients re-treated with a similar chemotherapy regimen.

Receptor-type tyrosine-protein phosphatase κ directly targets STAT3 activation for tumor suppression in nasal NK/T-cell lymphoma.

Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive disease characterized by frequent deletions on 6q, and constitutive activation of signal transducer and activator of transcription 3 (STAT3). Phosphorylation at Tyr705 activates STAT3, inducing dimerization, nuclear translocation, and DNA binding. In this study, we investigated whether receptor-type tyrosine-protein phosphatase κ (PTPRK), the only protein tyrosine phosphatase at 6q that contains a STAT3-specifying motif, negatively regulates STAT3 activation in NKTCL. PTPRK was highly expressed in normal NK cells but was underexpressed in 4 of 5 (80%) NKTCL cell lines and 15 of 27 (55.6%) primary tumors. Significantly, PTPRK protein expression was inversely correlated with nuclear phospho-STAT3(Tyr705) expression in NKTCL cell lines (P = .025) and tumors (P = .040). PTPRK restoration decreased nuclear phospho-STAT3(Tyr705) levels, whereas knockdown of PTPRK increased such levels in NKTCL cells. Phosphatase substrate-trapping mutant assays demonstrated the binding of PTPRK to STAT3, and phosphatase assays showed that PTPRK directly dephosphorylated phospho-STAT3(Tyr705). Restoration of PTPRK inhibited tumor cell growth and reduced the migration and invasion ability of NKTCL cells. Monoallelic deletion and promoter hypermethylation caused underexpression of PTPRK messenger RNA in NKTCL, and methylation of the PTPRK promoter significantly correlated with inferior overall survival (P = .049) in NKTCL patients treated with the steroid-dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide regimen. Altogether, our findings show that PTPRK underexpression leads to STAT3 activation and contributes to NKTCL pathogenesis.

[Changes in the expression of EphA5/ephrinA5 in the CA3 region of the hippocampus in rats with epilepsy and their role in the pathogenesis of temporal lobe epilepsy].

OBJECTIVE: To investigate the changes in the expression of EphA5 and its ligand ephrinA5 in the hippocampus of rats with epilepsy and their role in the pathogenesis of temporal lobe epilepsy (TLE). METHODS: A total of 240 Sprague-Dawley rats were randomly divided into control group and TLE group, with 120 rats in each group. A rat model of lithium-pilocarpine TLE was established, and then the rats were divided into subgroups at 12 and 24 hours and 7, 15, 30, and 60 days after epilepsy was induced. In-situ hybridization was used to measure the mRNA expression of ephrinA5 in the CA3 region and the dentate gyrus of the hippocampus in 9 rats; immunohistochemistry was used to measure the protein expression of EphA5 in the CA3 region and the dentate gyrus of the hippocampus in 9 rats; Neo-Timm silver staining was used to observe mossy fiber sprouting in the CA3 region of the hippocampus in 2 rats. RESULTS: In-situ hybridization showed mRNA expression of ephrinA5 in the CA3 region of the hippocampus, but this was not found in the dentate gyrus. Compared with the control group at the same time point, the TLE group had a significant reduction in the mRNA expression of ephrinA5 in the CA3 region of the hippocampus at 7 and 15 days after epilepsy was induced (P<0.05); at 30 and 60 days after epilepsy was induced, the TLE group had a gradual increase in the mRNA expression of ephrinA5 in the CA3 region of the hippocampus, and there was no significant difference between the TLE and control groups (P>0.05). Immunohistochemistry showed that EphA5 protein was expressed in the CA3 region and the dentate gyrus of the hippocampus and had a similar trend of change as ephrinA5 mRNA. Neo-Timm silver staining showed that the TLE group developed marked mossy fiber sprouting in the CA3 region of the hippocampus at 7 and 15 days after epilepsy was induced. CONCLUSIONS: Downregulation of ephrinA5 and EphA5 in the CA3 region of the hippocampus may participate in the mechanism of mossy fiber sprouting and is closely associated with the development and progression of epilepsy.

Differential Expression of Adenosine P1 Receptor ADORA1 and ADORA2A Associated with Glioma Development and Tumor-Associated Epilepsy.

Level of adenosine, an endogenous astrocyte-based neuromodulator, is primarily regulated by adenosine P1 receptors. This study assessed expression of adenosine P1 receptors, ADORA1 (adenosine A1 receptor) and ADORA2A (adenosine A2a receptor) and their association with glioma development and epilepsy in glioma patients. Expression of ADORA1/ADORA2A was assessed immunohistochemically in 65 surgically removed glioma tissue and 21 peri-tumor tissues and 8 cases of normal brain tissues obtained from hematoma patients with cerebral trauma. Immunofluorescence, Western blot, and qRT-PCR were also used to verify immunohistochemical data. Adenosine P1 receptor ADORA1 and ADORA2A proteins were localized in the cell membrane and cytoplasm and ADORA1/ADORA2A immunoreactivity was significantly stronger in glioma and peri-tumor tissues that contained infiltrating tumor cells than in normal brain tissues (p < 0.05). The World Health Organization (WHO) grade III gliomas expressed even higher level of ADORA1 and ADORA2A. Western blot and qRT-PCR confirmed immunohistochemical data. Moreover, higher levels of ADORA1 and ADORA2A expression occurred in high-grade gliomas, in which incidence of epilepsy were lower (p < 0.05). In contrast, a lower level of ADORA1/ADORA2A expression was found in peri-tumor tissues with tumor cell presence from patients with epilepsy compared to patients without epilepsy (p < 0.05). The data from the current study indicates that dysregulation in ADORA1/ADORA2A expression was associated with glioma development, whereas low level of ADORA1/ADORA2A expression could increase susceptibility of tumor-associated epilepsy.

[Expression of USP9X in Non-small Cell Lung Cancer and Its Clinical Significance].

OBJECTIVE: To investigate the expression and clinical significance of ubiquitin-specific protease 9X (USP9X) protein in non-small cell lung cancer (NSCLC). METHODS: USP9X proteins were detected in 71 cases of NSCLC and 20 cases of benign pulmonary tissues by immunohistochemical staining. The correlation between USP9X expression and 51 NSCLC clinicopathological parameters as well as survival rates were indicated. RESULTS: Higher rate [69. 0% (49/71)] of the expression of USP9X was observed in NSCLC samples, compared with 20. 0% (4/20) in benign pulmonary tissues (P<0. 001). Furthermore, the expression of USP9X proteins was positively associated with both histological types and lymph node metastasis (P<0. 05). The survival analysis showed that the survival rate was lower in patients with positive expressions of USP9X than in patients with negative expressions (P< 0. 05). USP9X expression, together with histological types and TNM stage was an independent predictor for overall survival in the multivariate Cox regression model (P < 0. 05). CONCLUSION: Up-regulation of USP9X plays an important role in the invasion and progression of NSCLC and could be considered as a prognostic predictor for NSCLC.

MicroRNA-34a induces apoptosis in the human glioma cell line, A172, through enhanced ROS production and NOX2 expression.

BACKGROUND: MicroRNA is a type of non-coding small RNA involved in regulating genes and signaling pathways through incomplete complementation with target genes. Recent research supports key roles of miRNA in the formation and development of human glioma. METHODS: The relative quantity of miR-34a was initially determined in human glioma A172 cells and glioma tissues. Next, we analyzed the impact of miR-34a on A172 cell viability with the MTT assay. The effects of miR-34a overexpression on apoptosis were confirmed with flow cytometry and Hoechst staining experiments. We further defined the target genes of miR-34a using immunofluorescence and Western blot. RESULTS: MiR-34a expression was significantly reduced in human glioma A172 cells and glioma tissue, compared with normal glial cells and tissue samples. Our MTT data suggest that up-regulation of miR-34a inhibits cell viability while suppression of miR-34a enhances cell viability. Flow cytometry and Hoechst staining results revealed increased rates of apoptosis in A172 human glioma cells overexpressing miR-34a. Using immunofluorescence and Western blot analyses, we identified NOX2 as a target of miR-34a in A172 cells. CONCLUSION: MiR-34a serves as a tumor suppressor in human glioma mainly by decreasing NOX2 expression.

[Prognostic analysis of 525 Chinese patients with diffuse large B cell lymphoma].

OBJECTIVE: To describe the clinical characteristics, overall survival as well as to evaluate the prognostic factors in Chinese diffuse large B cell lymphoma (DLBCL) patients. METHODS: DLBCL patients who were initially diagnosed and treated in Peking University Cancer Hospital from January 1995 to December 2008 were identified and analyzed,retrospectively.The 5-year OS rates were estimated with Kaplan-Meier. Log-rank test was used to compare the survival curves of the different groups. The multivariate analysis of prognostic factors was conducted with Cox regression model, which included all statistically significant prognostic factors in the univariate analyses. RESULTS: A total of 525 DLBCL patients were included in this retrospective analysis, of whom, 294 were male and 231 female (male:female=1.27:1). The median age at the initial diagnosis was 55 (range 16-90) years, and 37.0% (n=194) were 60 years and above. Regarding the clinical staging at the initial diagnosis, 54 patients (10.3%) were diagnosed as Stage I of the disease, 152 (28.9%) as Stage II, 117 (22.3%) as Stage III and 202 (38.5%) as Stage IV. The "B symptoms" and increased serum LDH were presented in 206 (39.2%) and 192 (36.6%) patients, respectively. A total of 197 (37.5%) patients were treated with rituximab (R). The survival follow-up continued till 31 January 2014 with a median follow-up time of 77.5 (range: 0-205) months. A total of 267 patients (50.9%) died during the follow-up period. The medial overall survival (OS) time was 84 months, and 5-year OS rate was 52.3%. There were six statistically significant prognostic factors that were identified in both univariate and multivariate analyses: gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment. The relative risk (RR) of these prognostic factors in the multivariate analyses were: age > 60 years / ≤ 60 years=1.380 (95%CI 1.078-1.765), male / female=1.315 (95%CI 1.025-1.687), stage III/stage I=3.034 (95%CI 1.667-5.522), stage IV/I=3.748(95%CI 2.102-6.681), with B symptoms/without B symptoms=1.278(95%CI 0.999-1.636), serum LDH increased/LDH not increased=1.351(95%CI 1.057-1.726), without R treatment / with R treatment=1.543 (95%CI 1.182-2.015).Compared with the IPI, age >50 years/ ≤ 50 years was a statistically significant factor in both univariate and multivariate analyses RR=1.478 (95%CI 1.148-1.902), P=0.002. CONCLUSION: Six factors were related to DLBCL survival: gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment. Compared with the IPI, several specific factors may predict a poor prognosis in Chinese DLBCL patients: male, age>50 years and the presence of "B symptoms". But this result is not conclusive until these factors are further tested.

[A clinicopathologic and prognosis study of Epstein-Barr virus positive diffuse large B-cell lymphoma in west-southern China].

OBJECTIVE: To investigate the clinicopathologic features, immunophenotype, and the prognosis related factors of Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) in west-southern China. METHODS: There were 42 cases of EBV+ DLBCL in a total 586 DLBCL, the clinical and pathologic profiles of these patients were evaluated. Immunohistochemical study and in situ hybridization (ISH) of EBER1/2 were performed on formalin fixed tissues by tissue chips. The prognosis related factors were analyzed. RESULTS: The median age of these 42 EBV+ DLBCL patients was 62.5 years. The male-to-female ratio was 2.23 : 1. The site of occurrence included lymph node (69.05%) and spleen, stomach, tonsil, nasal cavity and nasopharynx. The mostly common initial clinical presentations were non-specific symptoms, such as lymphadenopathy, splenomegaly, hepatomegaly, fever, and fatigue. Morphologically, the majority (90.48%, 38/42) were pleomorphic subtypes and only 4 cases (9.52%) were simplex subtypes. Immunophenotype showed non-GCB type of DLBCL was predominance (83.33%, 35/42) by Hans classification. The expression of CD30, CD5, BCL-2, P53 and NF-kappaB/ P65 were 52.38% (22/42), 54.76% (23/42), 54.76% (23/42), 87.5% (35/40) and 0% (0/40) respectively. Follow-up data was available in 23 (54.76%) patients, 14 (60.87%) patients died of the tumor. 5-years overall survival was 16.5%. The median survival time was 40 months. The expression of BCL-2, increased LDH level and starry-sky morphologic character were associated with a poor prognosis. CONCLUSION: EBV positive DLBCL is not uncommon. Most lesions locate in lymph nodes. Pleomorphic histologic subtype is predominant. The tumor has worse prognosis with increased LDH level, starry-sky morphologic character and BCL-2 expression.

Multisystem Erdheim-Chester disease presenting with pericardial effusion confirmed by the effusion cytology specimen.

Erdheim-Chester disease (ECD) is a rare histiocytosis characterized by the foamy CD68+CD1a- histiocytes infiltrating multiple organs and tissues. ECD might be asymptomatic or present with variable manifestations. The diagnosis of ECD requires characteristic radiological findings and pathological features. Herein, we described a 52-year-old female patient who was admitted to our hospital for recurrent pericardial effusion for two months. She has a medical history of papillary thyroid carcinoma (PTC) and underwent a total thyroidectomy two years before admission. The radiological findings suggested a potential diagnosis of ECD. Cytological analysis of the effusion cytology specimen revealed CD68+CD1a- histiocytes, confirming the ECD diagnosis. The BRAF V600E mutation was identified in the histiocytes, prompting the administration of vemurafenib, a BRAF inhibitor. After two months of standard-dose vemurafenib treatment, the disease was well controlled with pericardial effusion regression.

Histone methyltransferase KMT2D inhibits ENKTL carcinogenesis by epigenetically activating SGK1 and SOCS1.

BACKGROUND: Epigenetic alteration plays an essential role in the occurrence and development of extranodal natural killer/T cell lymphoma (ENKTL). Histone methyltransferase (HMT) KMT2D is an epigenetic regulator that plays different roles in different tumors, but its role and mechanism in ENKTL are still unclear. METHODS: We performed immunohistochemical staining of 112 ENKTL formalin-fixed paraffin-embedded (FFPE) samples. Then, we constructed KMT2D knockdown cell lines and conducted research on cell biological behavior. Finally, to further investigate KMT2D-mediated downstream genes, ChIP-seq and ChIP -qPCR was performed. RESULTS: The low expression of KMT2D was related to a decreased abundance in histone H3 lysine 4 mono- and trimethylation (H3K4me1/3). In KMT2D knockdown YT and NK-YS cells, cell proliferation was faster (P < 0.05), apoptosis was decreased (P < 0.05), the abundance of S phase cells was increased (P < 0.05), and the level of H3K4me1 was decreased. Notably, ChIP-seq revealed two crucial genes and pathways downregulated by KMT2D. CONCLUSIONS: KMT2D is a tumor suppressor gene that mediates H3K4me1 and influences ENKTL proliferation and apoptosis by regulating the cell cycle. Moreover, in ENKTL, serum- and glucocorticoid-inducible kinase-1 (SGK1) and suppressor of cytokine signaling-1 (SOCS1) are downstream genes of KMT2D.

Broad distribution of diverse anaerobic ammonium-oxidizing bacteria in chinese agricultural soils.

Anaerobic ammonium-oxidizing (anammox) bacteria have been detected in many marine and freshwater ecosystems. However, little is known about the distribution, diversity, and abundance of anammox bacteria in terrestrial ecosystems. In this study, anammox bacteria were found to be present in various agricultural soils collected from 32 different locations in China. Phylogenetic analysis of the 16S rRNA genes showed "Candidatus Brocadia," "Candidatus Kuenenia," "Candidatus Anammoxoglobus," and "Candidatus Jettenia" in the collected soils, with "Candidatus Brocadia" being the dominant genus. Quantitative PCR showed that the abundance of anammox bacteria ranged from 6.38 × 10(4) ± 0.42 × 10(4) to 3.69 × 10(6) ± 0.25 × 10(6) copies per gram of dry weight. Different levels of diversity, composition, and abundance of the anammox bacterial communities were observed, and redundancy analysis indicated that the soil organic content and the distribution of anammox communities were correlated in the soils examined. Furthermore, Pearson correlation analysis showed that the diversity of the anammox bacteria was positively correlated with the soil ammonium content and the organic content, while the anammox bacterial abundance was positively correlated with the soil ammonium content. These results demonstrate the broad distribution of diverse anammox bacteria and its correlation with the soil environmental conditions within an extensive range of Chinese agricultural soils.

The elicitation effect of pathogenic fungi on trichodermin production by Trichoderma brevicompactum.

The effects of six species of phytopathogenic fungi mycelia as elicitors on trichodermin yield by Trichoderma brevicompactum were investigated. Neither nonviable nor viable mycelia of Botrytis cinerea, Alternaria solani, Colletotrichum lindemuthianum, and Thanatephorus cucumeris demonstrated any elicitation on the accumulation of trichodermin. However, the production of trichodermin was increased by the presence of viable/nonviable Rhizoctonia solani and Fusarium oxysporum mycelia. The strongest elicitation effect was found at the presence of nonviable R. solani. At the presence of nonviable R. solani, the maximum yield of trichodermin (144.55 mg/L) was significantly higher than the Control (67.8 mg/L), and the cultivation time to obtain the maximum yield of trichodermin decreased from 72 h to 60 h. No difference of trichodermin accumulation was observed by changing the concentration of nonviable R. solani from 0.1 to 1.6 g/L. It was observed that the optimum time for adding nonviable R. solani is immediately after inoculation. The diameter of T. brevicompactum mycelial globule after 72 h cultivation with nonviable R. solani elicitor was smaller than that of the Control.

[Effect of doxorubicin on TRAIL resistance and TRAIL receptor expression in lymphoma cell line SNK-6 cells].

OBJECTIVE: To investigate the effect of doxorubicin on TRAIL resistance and TRAIL receptor expression in lymphoma cell line SNK-6 cells. METHODS: SNK-6 cells treated with doxorubicin at different concentrations alone or in combination with tumor necrosis factor related apoptosis inducing ligand (TRAIL). Cell proliferation was evaluated by MTT assay. Apoptosis and the expression of TRAIL receptors were determined by flow cytometry. RESULTS: MTT assay showed that treatment with 100 and 1000 ng/ml doxorubicin for 24 h, the survival rates of SNK-6 cells were (80.9 ± 7.2)% and (53.7 ± 2.8)%, significantly higher than that by treatment combined with 500 ng/ml TRAIL (64.9 ± 1.1)% and (34.0 ± 3.9)%, respectively (P < 0.05). Flow cytometry showed that after treatment with 100 and 1000 ng/ml doxorubicin for 48 h, the survival rates of SNK-6 cells were (69.9 ± 6.1)% and (31.1 ± 1.9)%, while treated in combination with 500 ng/ml TRAIL, the cell survival rates were (37.5 ± 6.4)% and (15.0 ± 1.8)%, respectively. The early apoptosis rate was (14.8 ± 0.6)% and (30.8 ± 1.5)%, significantly lower than that [(28.7 ± 0.6)% and (46.6 ± 2.8)%] after treatment in combination with TRAIL (P < 0.05). The expressions of TRAIL receptors and decoy receptors were increased when SNK-6 cells were treated with 100 ng/ml doxorubicin for 24 hours. CONCLUSIONS: Doxorubicin can overcome to a certain extent the TRAIL resistance of SNK-6 cells and induce upregulation of TRAIL death receptors and decoy receptors on the surface of SNK-6 cells. However, a higher dose is needed.