Weipeng Zhao

[Effect of PI3Kδ inhibitor CAL-101 on myeloma cell lines and preliminary study of synergistic effects with other new drugs].

OBJECTIVE To investigate the proliferation inhibitory role and mechanism of PI3Kδ inhibitor CAL-101 on multiple myeloma (MM) cells, and to provide new therapeutic options for MM treatment. METHODS MM cell lines U266 and RPMI8226 cells were treated with various concentrations of CAL-101. MTT assay and CalcuSyn software were performed to determine the inhibitory effect of CAL-101 and the synergistic effect with PCI- 32765, SAHA (suberoylanilide hydroxamic acid), BTZ (Bortezomib) on MM cells. The protein expression level of p-AKT, p-ERK, AKT, ERK and PI3Kδ processed by CAL-101 were analyzed by Western blot. RESULTS CAL-101 at concentration of 15, 20, 25, 30 and 40 μmol/L could induce significant dose-dependent proliferation inhibition on U266 cells after treatment for 48 hours. The cell proliferation inhibition rates were (33.54 ± 1.23)%, (41.72 ± 1.78)%, (53.67 ± 2.01)%, (68.97 ± 2.11)% and (79.25 ± 1.92)%, respectively. Similar results were found in RPMI8226 cell line. Western blots showed high expression level of p-AKT, p-ERK, AKT, ERK and PI3Kδ in cell lines and MM primary cells. p-AKT and p-ERK protein expression levels were down-regulated significantly by CAL-101 treatment. Synergistic effect has been verified between CAL-101 and PCI-32765, SAHA and Bortezomib in U266 cell line, and PCI-32765, Bortezomib in RPMI8226 cell line with CI values less than 1. CONCLUSION CAL-101 could inhibit proliferation of MM cell lines. High levels of p-AKT, p-ERK, AKT, ERK and PI3Kδ protein expression were observed in both cell lines and primary cells. Down-regulation of p-AKT and p-ERK probably related with the mechanism of CAL-101 in MM cell proliferation inhibition. CAL-101 has significant synergistic effect with PCI-32765, SAHA and BTZ.

Toll-like receptor 4-induced inflammatory responses contribute to the tumor-associated macrophages formation and infiltration in patients with diffuse large B-cell lymphoma

To evaluate the expression of tumor-associated macrophages (TAMs) and Toll-like receptor 4 (TLR4) in diffuse large B-cell lymphoma (DLBCL) and their correlation with patient clinical characteristics, we detected using immunohistochemistry in 81 specimens of patients with DLBCL. The correlation between protein expression levels and clinical parameters, as well as the association between CD68 and TLR4 were analyzed. The number of CD68 TAMs was closely related to β2-microglobulin (P = .028 and P < .05), whereas there was no significant correlation between the number of CD68 TAMs and other clinical factors. Toll-like receptor 4 was related to tumor size and peripheral blood lymphocyte to monocyte ratio. The Spearman correlation coefficient indicated a significant positive correlation between CD68 TAMs and TLR4 expression (r = 0.240; P = .038, P = .05). These results, on one hand, indicated that TLR4-induced inflammatory responses may affect TAM infiltration and accumulation, and that TAMs and TLR4 may interact to play important roles in DLBCL microenvironment regulating the tumor growth, but, on the other hand demonstrated that both of TAMs and TLR4 had not only one side on DLBCL growth.

[The clinical and pathological characteristics of 14 patients' nodular lymphocyte predominant Hodgkin's lymphoma].

目的 探讨结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）患者的临床病理特征及疗效。 方法 收集14例NLPHL患者的临床资料，对其临床病理特征及近、远期疗效进行相关性分析。 结果 14例患者均为初治者，男、女各7例，中位发病年龄38（13～54）岁，中位随访时间为55.5（23～189）个月。发病率占同期霍奇金淋巴瘤（HL）的6.3%（14/223）。免疫组织化学检查结果示14例患者CD20均呈（+）/弱（+），CD30均（−），仅1例患者呈CD15弱（+）。14例患者中13例因自觉浅表淋巴结肿大就诊，所有患者惰性起病，病情进展缓慢。7例患者采用单纯化疗，7例患者采用放、化疗联合治疗。14例患者均有效，其中完全缓解（CR）+未证实的CR（CRu）12例。5年无疾病生存率为85.7%，5年总生存率为100.0%。单纯化疗与放、化疗联合治疗相比，不同的化疗方案相比，其近、远期疗效差异均无统计学意义（P值均>0.05）。 结论 NLPHL患者瘤细胞呈CD20（+）/弱（+），CD30（−），极少数患者呈CD15弱（+）。NLPHL在HL患者中所占比例低，以中青年患者多见，起病缓慢，与经典型HL患者相比疗效较好。