MLL5基因敲除对小鼠结肠癌CT26细胞移植瘤生长的影响及其机制

目的：探讨混合谱系白血病5(MLL5)基因在小鼠结肠癌CT26细胞移植瘤生长中的作用及其分子机制。方法：利用CRISPR/Cas9技术构建MLL5基因缺失、MLL5和DDX58双基因缺失的结肠癌CT26细胞模型,用Sanger测序和WB法验证敲除效果。将基因敲除的CT26细胞接种到野生型BALB/c小鼠和免疫缺陷型NSG小鼠皮下,构建基因缺失结肠癌CT26细胞移植瘤小鼠模型,并观察移植瘤的生长及荷瘤小鼠的总生存期（OS）。结果：在野生型小鼠中,MLL5基因缺失的CT26细胞移植瘤生长速度显著性低于野生型癌细胞移植瘤,并延长荷瘤小鼠的OS(P<0.01);在NSG小鼠中,MLL5基因缺失对CT26细胞移植瘤的生长速度以及荷瘤小鼠的OS没有明显改变。MLL5基因缺失提高了癌细胞中视黄酸诱导基因1(RIG-1)蛋白水平,DDX58基因缺失可逆转MLL5基因缺失在CT26细胞移植瘤中的作用。结论：MLL5基因缺失可提高结肠癌CT26细胞中RIG-1蛋白水平、促进肿瘤免疫,从而抑制荷瘤小鼠肿瘤生长,提示MLL5可能成为结肠癌治疗的新靶点。     

Analysis of anti‐apoptotic PVT1 oncogene and apoptosis‐related proteins (p53, Bcl2, PD‐1, and PD‐L1) expression in thyroid carcinoma

BackgroundAn aberrant expression of long non‐coding RNA PVT1 has been associated with apoptosis in various cancer types. We aimed to explore the PVT1 and four apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) signature in thyroid cancer (TC).MethodsThe PVT1 expression level was measured in 64 FFPE TC paired samples by real‐time quantitative PCR. Overall and stratified analyses by different clinicopathological features were done. The apoptotic proteins were evaluated by immunohistochemistry staining.ResultsOverall analysis showed significant PVT1upregulation in TC tissues (p < 0.001). Similarly, subgroup analysis by BRAF ^V600E mutation showed consistent results. Lower expression of p53 was associated with mortality (p = 0.001). Bcl2 overexpression was associated with greater tumor size (p = 0.005). At the same time, HCV‐positive cases were associated with repressed Bcl2 expression levels (54.3% in HCV‐negative vs. 6.9% in HCV‐positive cases, p = 0.011). PD‐1 expression was associated with lymph node metastasis (p = 0.004). Enhanced PD‐L1 expression in the tumor was associated with a higher tumor stage, lymphovascular invasion, and mortality risk. Kaplan–Meier curves for overall survival showed that low p53 and high PD‐L1 expressions were associated with lower survival time. The p53‐positive staining is associated with a 90% decreased mortality risk (HR = 0.10, 95%CI = 0.02–0.47, p = 0.001), while patients with high PD‐L1 were five times more likely to die (HR = 4.74, 95%CI = 1.2–18.7, p = 0.027).ConclusionOur results confirm the upregulation of PVT1 in TC. The apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) showed different prognostic utility in TC patients; in particular, low p53 and high PD‐L1 expressions associated with low survival times. Further large‐scale and mechanistic studies are warranted.     

Circ_SAR1A regulates the malignant behavior of lung cancer cells via the miR‐21‐5p/TXNIP axis

BackgroundLung cancer is one of the most common malignancies globally and a significant component of cancer‐related deaths. The lack of early diagnosis accounts for detecting approximately 75% of cancer patients at an intermediate to an advanced stage, with a low 5‐year survival rate. Therefore, a more comprehensive understanding of the molecular mechanisms of lung cancer development is necessary to find reliable and effective therapeutic and diagnostic biomarkers.Methodscirc_SAR1A, miR‐21‐5p, and TXNIP in lung cancer tissues, animal xenografts, and cell lines were validated by qRT‐PCR and western blotting analyses. RNase R digestion and nuclear/cytoplasm fractionation experiments were utilized to determine the stability and localization of circ_SAR1A in lung cancer cells. The binding between miR‐21‐5p and circ_SAR1A or TXNIP was confirmed by luciferase reporter, RNA pull‐down, Spearman''s correlation, and rescue assays. CCK‐8, colony formation, flow cytometry, Transwell, and western blotting were utilized to illustrate the malignant behavior of lung cancer cells.Resultscirc_SAR1A and TXNIP were down‐regulated while miR‐21‐5p was up‐regulated in lung cancer samples and cells. circ_SAR1A was located predominantly in the cytoplasm; it inhibited lung cancer growth in vitro and in vivo by sponging to miR‐21‐5p. miR‐21‐5p silencing suppressed lung cancer malignancy by targeting TXNIP.Conclusionscirc_SAR1A is a critical negative regulator of lung carcinogenesis. circ_SAR1A/miR‐21‐5p/TXNIP attenuation inhibited lung cancer progression, presenting an ideal diagnostic and a potential therapeutic target.     

Application of collagen triple helix repeat containing‐1 and mitotic spindle apparatus antibody in small cell lung cancer diagnosis

BackgroundThe clinical significance of serum collagen triple helix repeat protein‐1 (CTHRC1) and mitotic spindle apparatus antibody (MSA) in the diagnosis of small cell lung cancer (SCLC).MethodsOf the 229 lung tumor patients selected, 62 patients were divided into SCLC, 94 patients with non‐small cell lung cancer (NSCLC), and 73 patients with benign lung disease (BLD). The health controls (HC) had a span of 66 cases with normal physical condition. The serum extracted from each participator and enzyme‐linked immunosorbent assay was adopted for measuring the serum CTHRC1 and MSA; in the meantime, automatic electrochemiluminescence immunoassay was used for the quantitative determination of serum NSA and CEA. And then, the differences in serum CTHRC1, MSA, NSE, and CEA were compared among involved groups.Results① Compared with other groups, the concentrations of CTHRC1, MSA, and NSE showed a marked increase in the group of SCLC (all p < 0.01). Especially for SCLC patients with lymph node metastasis, CTHRC1 provided a notably higher level than those without metastasis. ② CTHRC1 and MSA established a diagnostic criterion with the specificity of 90.99% and 86.27% for SCLC, respectively. ③ In series, the specificity of CTHRC1 and NSE was the highest (99.30%), while MSA and NSE had the highest sensitivity (96.72%) in parallel. ④ Both CTHRC1 and MSA were hazardous factors interconnected with SCLC.ConclusionSerum CTHRC1 and MSA had a more exciting prospect of application. When used in conjunction with NSE and CEA, they could optimize the clinical diagnosis value of SCLC.     

Red blood cell distribution width‐to‐albumin ratio is associated with all‐cause mortality in cancer patients

BackgroundCancer causes a serious health burden on patients worldwide. Chronic low‐level inflammation plays a key role in tumorigenesis and prognosis. However, the role of the red blood cell distribution width (RDW)‐to‐albumin (RA) ratio in cancer mortality remains unclear.MethodsIn this retrospective cohort study, we collected clinical information from cancer patients from the Medical Information Mart for Intensive Care III (MIMIC‐III) version 1.4 database and then calculated RA by dividing RDW by albumin concentration. The primary outcome was 30 days mortality, while secondary outcomes were 90 days and 1 year mortality. Next, we adopted Cox regression models to calculate hazard ratios (HR) together with 95% confidence intervals (CI) for all‐cause mortalities associated with the RA ratio.ResultsFor 30 days mortality, the HR (95% CI) for the high RA ratio (≥5.51) was 2.17 [95CI% (1.87–2.51); p = <0.0001], compared with the low RA ratio (<5.51). In Model 2, we adjusted sex and age and obtained HR (95% CI) of 2.17 [95CI% (1.87–2.52); p = <0.0001] for the high RA ratio (≥5.51) group, compared to that in the low RA ratio (<5.51). In Model 3, adjusting for age, sex, anion gap, hematocrit, white blood cell count, congestive heart failure, SOFA, liver disease, and renal failure resulted in HR (95% CI) of 1.74 [95CI% (1.48–2.04); p = <0.0001] for the high RA ratio (≥5.51) relative to the low RA ratio (<5.51). We also analyzed common diseases in cancer patients but found no significant association.ConclusionTo the best of our knowledge, this is the first study demonstrating that increased RA ratio is independently associated with increased all‐cause mortality in cancer patients.     

Smart Bone Graft Composite for Cancer Therapy Using Magnetic Hyperthermia

Magnetic hyperthermia (MHT) is a therapy that uses the heat generated by a magnetic material for cancer treatment. Magnetite nanoparticles are the most used materials in MHT. However, magnetite has a high Curie temperature (Tc~580 °C), and its use may generate local superheating. To overcome this problem, strontium-doped lanthanum manganite could replace magnetite because it shows a Tc near the ideal range (42–45 °C). In this study, we developed a smart composite formed by an F18 bioactive glass matrix with different amounts of Lanthanum-Strontium Manganite (LSM) powder (5, 10, 20, and 30 wt.% LSM). The effect of LSM addition was analyzed in terms of sinterability, magnetic properties, heating ability under a magnetic field, and in vitro bioactivity. The saturation magnetization (M_s) and remanent magnetization (M_r) increased by the LSM content, the confinement of LSM particles within the bioactive glass matrix also caused an increase in Tc. Calorimetry evaluation revealed a temperature increase from 5 °C (composition LSM5) to 15 °C (LSM30). The specific absorption rates were also calculated. Bioactivity measurements demonstrated HCA formation on the surface of all the composites in up to 15 days. The best material reached 40 °C, demonstrating the proof of concept sought in this research. Therefore, these composites have great potential for bone cancer therapy and should be further explored.     

肺癌根治术后局部复发的多因素分析

目的回顾性分析118例肺癌根治术后患者的局部复发预后因素,探讨肺癌术后辅助放疗的指征。方法收集2007年6月～2009年6月共118例肺癌根治术后患者,记录其相关的临床病理因素及局部复发情况,用Kaplan-Meier法计算无复发生存率,用Log-rank法和Cox模型分别进行单因素和多因素预后分析,分析影响局部复发的预后因素。结果随访率100%。随访时间为随访6～55个月,中位数27个月。1年、2年、3年无复发生存率分别为73.1%、61.8%、56.3%,中位复发时间为10个月。单因素分析结果显示术前CEA升高、术前贫血、肿瘤大小、T分期、N分期等为影响局部复发的因素,多因素分析结果显示术前CEA升高、T分期、N分期等为影响局部复发的独立预后因素。结论术前CEA水平、T分期以及N分期是肺癌根治术后局部复发的独立预后因素,对于此类患者,局部复发风险高,可能需要更进一步的治疗,如辅助放疗等。     

腹腔镜手术治疗59例子宫颈癌患者的近期疗效观察

目的 探讨腹腔镜手术在宫颈癌治疗中的临床价值.方法 将2010年10月～2013年6月行宫颈癌根治术的132例Ⅰ a2～Ⅱa2期的宫颈癌患者分为腹腔镜组和开腹组,比较两组的手术时间、淋巴结切除数、术中出血量、术后病理等指标.结果 59例宫颈癌腹腔镜手术均顺利完成,其术后病理结果、并发症、切除淋巴结数与开腹手术均无明显差异（P＞0.05）,但其手术时间、术后并发症、出血量、术后补充治疗间隔时间较开腹组少（P＜0.05）.结论 腹腔镜下手术治疗子宫颈癌安全可靠.     

联合方案与吉西他滨加顺铂单纯化疗方案治疗晚期非小细胞肺癌的对比研究

①目的 比较TM-GP方案、[timogpntin(胸腺五肽)、MA(megestrol acetate,甲地孕酮)、吉西他滨与顺铂(DDP)联合的生物化疗方案]与GP方案(即吉西他滨加DDP的单纯化疗方案)对初治Ⅲ～Ⅳ期非小细胞肺癌(NSCLC)患者的疗效、毒性及生活质量的改善情况.②方法 A组(33例)接受TM-GP方案治疗;B组(35例)接受GP方案治疗.两组均以4周为1周期,重复3个周期.客观疗效与毒性反应按世界卫生组织(WHO)标准进行评价,生活质量根据临床受益疗效来评价.③结果 A、B两组客观疗效总有效率(CR+PR)分别为27.3%及22.9%(P>0.05);中位生存期A组32周,B组27周(P<0.01);白细胞减少及恶心呕吐反应B组均较A组明显(P<0.01);短暂性寒战、发热症状多见于A组(P<0.01);两组均未发现其他严重的毒性反应.临床受益疗效A组高于B组(P<0.05).④结论 胸腺五肽、甲地孕酮配合GP方案与单纯GP方案治疗晚期NSCLC的客观疗效无明显差异性,但前者毒副反应小,中位生存期长,患者生活质量改善明显.