Long-term, 13-year survival after immune cell therapy combined with chemotherapy for extensive-stage small-cell lung cancer: a case report.

While the incidence of small-cell lung cancer is low, it has a poor prognosis. Patients with extensive small-cell lung cancer account for about 70% of all cases of small-cell lung cancer, with a median overall survival duration of 8-13 months and a 5-year overall survival rate of only 1%-5%. Herein, we report small-cell lung cancer diagnosed by bronchoscopic biopsy in an adult male patient in 2011. The patient had a clinical stage of cT2N2M1 and stage IV disease (i.e., extensive small-cell lung cancer). Still, he survived for 13 years through a combination of chemotherapy, radiotherapy, and cytokine-induced killer (CIK) immunocell thera. Comprehensive tumor markers, lymphocyte subsets, and lung CT images were obtained through long-term follow-up. After 12 cycles of chemotherapy (CE/IP regimen) and 5940cgy/33f radiotherapy, we found that the patient was in an immunosuppressive state, so the patient was given CIK cell therapy combined with chemotherapy. After 2 years of immunocell-combined chemotherapy, there were no significant changes in the primary lesion or other adverse events. In the 13 years since the patient's initial diagnosis, we monitored the changes in the patient's indicators such as CEA, NSE, CD4/CD8 ratio, and CD3+CD4+ lymphocytes, suggesting that these may be the factors worth evaluating regarding the patient's immune status and the effectiveness of combination therapy. In this case, CIK cell immunotherapy combined with chemotherapy was applied to control tumor progression. With a good prognosis, we concluded that CIK cell immunotherapy combined with chemotherapy can prolong patient survival in cases of extensive small-cell lung cancer, and the advantages of combined therapy are reflected in improving the body's immune capacity and enhancing the killing effect of immune cells.

Exercise reduces hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient mice via its effects against inflammation and oxidative stress.

Cardiovascular disease is a high incidence and mortality rate disease worldwide. Exercise training has become an established evidence-based treatment strategy that is beneficial for many cardiovascular diseases. This study aimed to investigate the effects of exercise on hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient (ApoE-/-) mice. Male ApoE-/- mice were randomly divided into the following four groups: normal diet (ND), normal diet + exercise training (ND + E), high-fat diet (HFD), and high-fat diet + exercise training (HFD + E). Exercise training consisted of swimming for 40 min, 5 days/week for 12 weeks. After 12 weeks, histopathological alterations in cardiac tissue and the serum were measured. Furthermore, the NOX4, NRF2, SIRT1, TGF-ß, HO-1, collagen III, Smad3, Bax, Bak, Bcl-2, Bcl-xl, IL-1ß, IL-6, and IL-18 expression levels were evaluated using immunohistochemistry and western blotting; Results: the serum levels of SIRT1, GSH-Px, and SOD were lower in ApoE-/- HFD mice compared with those in ApoE-/- HFD + E mice. Significant pathological changes were observed in the ApoE-/- HFD + E group compared with those in the ApoE-/- HFD group. Increased levels of oxidative stress, fibrosis, and apoptosis, and decreased antioxidant expression in the ApoE-/- HFD group compared with those in ApoE-/- HFD + E mice. Exercise exerts protective effects against cardiac damage caused by hyperlipidemia.

Puerarin suppression of Aß1-42-induced primary cortical neuron death is largely dependent on ERß.

Recent study has suggested that estrogen replacement therapy (ERT) can decrease the risk of the development of Alzheimer's disease (AD), and phytoestrogen has been proposed as a potential alternative to ERT. In this study, we investigated the protective function of puerarin (a phytoestrogen isolated from puerarin lobate) against amyloid beta (Aß1-42)-induced toxicity in cortical neurons and established the connection between such a protection and estrogen receptor (ER) activation. Puerarin suppressed Aß1-42-induced cortical neuron death in a concentration-dependent manner. Morphological examination showed that puerarin not only suppressed Aß1-42-induced decrease in neuron numbers, but also promoted neurite growth. In addition, we found that the neuroprotection of puerarin was dependent on the activation of estrogen receptors (ERs), as demonstrated by activation of ERE-reporter gene. Puerarin preferentially up-regulated the expression of ERß but not ERα, and ERß-specific siRNA significantly reduced the neuroprotection of puerarin. Taken together, our results indicated that puerarin is neuroprotective against Aß1-42 toxicity via the activation of estrogen receptors, and ERß plays a key role in the process. Our novel findings provide a potential strategy for the prevention of neurodegeneration and the treatment of AD.

Effect of cytokine-induced killer cells on immune function in patients with lung cancer.

Cytokine-induced killer (CIK) cells have been used as adoptive immunotherapy in cancer. The present study evaluated the effect of CIK cells on immune function in patients with lung cancer. Patients were divided into three groups, according to the treatment received prior to CIK cell treatment: CIK group (no prior treatment), Che-Sur group (prior chemotherapy and surgery) and Che-Rad group (prior chemotherapy and radiotherapy). Following treatment, the average percentage of cluster of differentiation (CD)3+CD4+, CD3+, natural killer (NK) and NKT cells in peripheral blood was significantly higher than that prior to CIK treatment in the Che-Sur and CIK groups, and the levels of interferon-γ in serum were significantly higher than those prior to CIK treatment in the Che-Sur and CIK groups. On the contrary, the levels of interleukin-10 had decreased in these groups following CIK treatment. Subsequently, patients were divided into three groups according to the percentage of CD3+CD56+ CIK cells that were administered to the patients. The number of NK and NKT cells increased with increasing number of CD3+CD56+ cells. The patients in the CIK and Che-Sur groups were the most benefited ones following CIK treatment, contrarily to those in the Che-Rad group, since the increase in the number of CD3+CD56+ CIK cells in the aforementioned patients enhanced the number of NK cells, which exhibit antitumor activity.

Treatment efficacy of MUC1-DC vaccine in breast cancer MCF-7 cell xenografts in nude mice evaluated by monitoring tumor growth with optical molecular imaging / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：评价黏蛋白1（mucin 1，MUC1）基因转染的DC疫苗治疗乳腺癌MCF-7细胞裸鼠移植瘤的效果及其可能的机制。方法：采用GFP慢病毒转染MCF-7细胞获得GFP-MCF-7细胞，皮下种植于BALB/c裸鼠，成瘤后随机分为3组。各组裸鼠首先尾静脉注射体外活化的CIK细胞（1×108个/只），治疗组于皮下注射MUC1基因转染的MUC1-DC（MUC1-DC组）或DC（DC组）（0.2 ml，1×107个/只），对照组（Control组）注射等体积生理盐水，每天治疗1次，连续5 d；采用小动物活体光学成像系统在开始治疗前及治疗后第35天观察移植瘤荧光成像，分析荧光强度和荧光面积；并采用免疫组化法检测瘤组织中Caspase 3的表达、TUNEL法检测细胞凋亡率。结果：GFP-MCF-7接种后7 d，成瘤率100%；光学分子成像法监测结果显示，治疗前MUC1-DC组、DC组和Control组之间体内移植瘤荧光信号强度无明显差异（P>0.05）；第35天，MUC1-DC组的荧光信号强度明显低于Control组（P<0.05）；DC与Control、MUC1-DC与DC组间均无显著性差异（均为P>0.05），但MUC1-DC比DC组荧光信号更低；治疗前MUC1-DC组、DC组和Control组之间体内移植瘤荧光信号分布面积无显著差异（P>0.05）；第35天，Control组荧光信号呈多处散在分布，MUC1-DC组和DC组的荧光信号面积均明显低于Control组（均为P<0.01），MUC1-DC组的荧光信号面积低于DC组，但无显著差异（P>0.05）；Control组Caspase 3表达最少，DC组次之，MUC1-DC组呈高表达Caspase 3，3组间差异均有统计学意义（均为P<0.05）；3组细胞凋亡率分别为：Control组（4.11±2.61）%、DC组（9.63±2.27）%、MUC1-DC组（25.30±8.24）%，3组间差异均有统计学意义（均P<0.05）。结论： MUC1-DC疫苗比单纯DC免疫治疗人乳腺癌荷瘤小鼠能够更有效地抑制肿瘤的生长和扩散，发挥了更好的促进肿瘤细胞凋亡的作用。

Synergistic anti-tumor effect of KLF4 and curcumin in human gastric carcinoma cell line.

Kruppel-like factor 4 is a transcription factor which plays an important role in development and progression of various carcinomas. Curcumin characterized by excellent anti-cancer properties is regarded as a serviceable natural compound used in carcinoma therapy. This study aimed at exploring the impact of KLF4 overexpression in cooperation with curcumin on the proliferation, apoptosis and invasion of human gastric carcinoma BGC- 823 cells. Flow cytometry analysis, CCK-8 assays, transwell assays and Western blot results showed that KLF4 overexpression combined with curcumin had significant anti-proliferation, pro-apoptosis and anti-invasion effects on BGC-823 cells. We also found that KLF4 had synergistic effects with curcumin, better promoting apoptosis and inhibiting proliferation and invasion of gastric carcinona cells. These results indicate that KLF4 could be used as a potential therapeutic target; curcumin could act as an auxiliary and provide a promising therapeutic strategy in stomach cancer.

Effects of resibufogenin on voltage-gated sodium channels in cultured rat hippocampal neurons.

Voltage-gated sodium channels (VGSCs) play important roles in maintaining the excitability of hippocampal neurons. The present study investigated the effects of resibufogenin (RBG, a main component of bufadienolides) on voltage-gated sodium channel currents (I(Na)) in rat hippocampal neurons using whole-cell patch clamp recording. According to the results, RBG activated I(Na) in a concentration-dependent manner. RBG at 1 µM concentration could alter some channel kinetics of I(Na), such as activation thresholds, steady-state activation and inactivation curves, time constant of recovery, and activity-dependent attenuation of I(Na). RBG influenced peak amplitude, overshoot and half-width of the evoked single action potential, and simultaneously lessened the firing rate of evoked repetitive firing. These findings suggested that I(Na) is probably a target of RBG, which may explain the mechanisms for the pathological effects of RBG on central nervous system.

Effects of Resibufogenin and Cinobufagin on voltage-gated potassium channels in primary cultures of rat hippocampal neurons.

Outward delayed rectifier potassium channel and outward transient potassium channel have multiple important roles in maintaining the excitability of hippocampal neurons. The present study investigated the effects of two bufadienolides, Resibufogenin (RBG) and Cinobufagin (CBG), on the outward delayed rectifier potassium current (IK) and outward transient potassium current (IA) in rat hippocampal neurons. RBG and CBG have similar structures and both were isolated from the venom gland of toad skin. RBG inhibited both IK and IA, whereas CBG inhibited IK without noticeable effect on IA. Moreover, at 1 µM concentration both RBG and CBG could alter some channel kinetics and gating properties of IK, such as steady-state activation and inactivation curves, open probability and time constants. These findings suggested that IK is probably a target of bufadienolides, which may explain the mechanisms of bufadienolides' pathological effects on central nervous system.