Anticancer activity of Honokiol against lymphoid malignant cells via activation of ROS-JNK and attenuation of Nrf2 and NF-κB.

PURPOSE: To evaluate the effect of Honokiol (HK) in the ROS-JNK pro-apoptotic pathway and NF-κB, Nrf2 anti-apoptotic pathways, in order to seek a possible explanation for its anticancer efficacy. METHODS: The Raji and Molt4 cell lines were utilized for the determination of anticancer activity against lymphoid malignant cells. BALB/C nude mice, weighing 18-20g each and aged 4-5 weeks, were procured from the central animal house facility. For establishing non-Hodgkin lymphoma in BALB/C, the nude mice were subcutaneously administered 1×10(7) Raji cells, suspended in 0.2 mL sterile PBS on the back. The mice were then randomly divided into 3 groups (6 mice in each group). HK cytotoxicity was determined using the colorimetric MTT assay. RESULTS: In colorimetry-based MTT assay, the cytotoxicity of HK was determined at different time intervals, in lymphoid malignant Raji and Molt4 cell lines. HK exhibited prominent cytotoxicity against Raji cell lines with IC50 of 0.092 ± 0.021 µM. In Molt4 cells, the administration of HK caused significant cytotoxicity with IC50 of 0.521 ± 0.115 µM. The treatment of HK caused significant increase in the activity of reactive oxygen species (ROS) in Raji cells at various time intervals. Moreover, the level of NF-κB was significantly reduced in the presence of HK, which could be easily understood by a decreased level of p-65. Furthermore, in the presence of ROS inhibitor NAC (10mM) for 24 hrs, the JNK pathway was markedly activated, together with inhibition of NF-κB activity and a reduced level of Nrf2 expression. To further confirm the in vitro results by in vivo activity, HK was observed to inhibit the proliferation of Raji cells in vivo, which might be attributable to its inhibitory effect against the progression of the tumor (p<0.05). CONCLUSION: The present study suggests that HK causes considerable induction of apoptosis in lymphoid malignant cells, both in vitro and in vivo, whereas the generation of ROS might serve as an underlying mechanism for inducing apoptosis.

Chronic myelomonocytic leukemia-associated pulmonary alveolar proteinosis: A case report and review of literature.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare condition that can cause progressive symptoms including dyspnea, cough and respiratory insufficiency. Secondary PAP is generally associated with hematological malignancies including chronic myelomonocytic leukemia (CMML). To the best of our knowledge, this is the first reported case of PAP occurring secondary to CMML. CASE SUMMARY: We report the case of a 63-year-old male who presented with a recurrent cough and gradually progressive dyspnea in the absence of fever. Based upon clinical symptoms, computed tomography findings, bone marrow aspiration, flow cytometry studies and cytogenetic analyses, the patient was diagnosed with PAP secondary to CMML. He underwent whole lung lavage in March 2016 to alleviate his dyspnea, after which he began combined chemotherapeutic treatment with decitabine and cytarabine. The patient died in January 2020 as a consequence of severe pulmonary infection. CONCLUSION: This case offers insight regarding the mechanistic basis for PAP secondary to CMML and highlights potential risk factors.

[Prognostic Value of Morphology and Hans Classification in Diffuse Large B Cell Lymphoma].

OBJECTIVE: To investigate the prognostic value of morphology and Hans classification in diffuse large B cell lymphoma（DLBCL）. METHODS: Clinical data of 249 patients diagnosed with DLBCL in our hospital and Hangzhou Xixi hospital during Jan 2006 to Dec 2016 were analyzed retrospectively. These patients were classified into 3 groups: immunoblastic variant（IB） group, centroblastic variant（CB） group and others group according to the cell morphology. And DLBCL was also divided into GCB（germinal center B-cell-like）or non-GCB（non-germinal center B-cell-like） group by analyzing the expression of CD10, BCL6 and MUM1 (GCB: CD10 +,BCL6+-,MUM1+-/CD10-,BCL6+,MUM1-；non-GCB：CD10-,BCL6-,MUM1+-/CD10-,BCL6+,MUM1+). RESULTS: The univariate analysis displayed that the age，LDH level，IPI，IB，non-GCB，B-symptoms and rituximab all could influence the OS and EFS, the CR rate of CB subtype patients was significantly higher than that of the patients with IB subtype （68.3% vs 38.9%)(P=0.02）. IB subtype was the in dependent prognostic factor for both EFS and OS in the whole study. In multivariate analysis, IPI and IB were the independent prognostic factors for OS and EFS. IB subtype was also an independent prognostic factor in EFS and OS with or without rituximab. The expression of BCL2 and BCL6 was related with prognosis in R-CHOP, but not in CHOP treated patients. Other markers (CD5, CD10, IRF4/MUM1, HLA-DR and Ki-67 proliferation index) were not of the significant prognostic value for DLBCL. When accepted rituximab, the GCB and non-GCB were not different significantly for prognosis. However, the non-GCB group showed a poor prognosis without using rituximab （EFS P=0.020；OS P=0.020）. Multivariate Cox models showed that OS and EFS were not significantly different between GCB and non-GCB group, however, the IB subtype had a very significantly poor prognosis in OS and EFS (P=0.001, P=0.002). When the analysis was restricted to DLBCL with CB morphology only, no prognostic value was observed in Hans classification. CONCLUSION: The subtype of immunoblast is a major risk factor in patients treated with CHOP or R-CHOP. There is a significant association between the Hans classification and the morphologic subclassification. Results of this study have supplemented the data for the prognostic factor of DLBCL and demonstrated that the cytomorphologic diagnosis can be reproducible.

[Expression and activity of membrane surface tissue factor in peripheral blood cells of patients with cerebral infarction].

This study was aimed to investigate the expression and activity of membrane surface tissue factor (TF) of monocytes and platelets in peripheral blood cells from patients with cerebral infarction and their clinical significance. The TF expressions in monocytes and platelets from 25 patients with cerebral infarction were detected by flow cytometry, the TF activity was detected by chromogenic reaction method, and compared with 24 normal people used as control. The results showed that the TF expressions of monocytes and platelets in peripheral blood cells from patients with cerebral infarction were significantly higher than that in normal controls (p<0.01), and TF activity was also higher in patients than that in controls (p<0.01). In conclusion, the expression and activity of membrane surface in patients with cerebral infarction were enhanced, the hematocyte-derived tissue factor as a trigger in coagulation pathway is involved in pathological thrombosis in patients with cerebral infarction.