中药复方“冬夏丸”体外对6株人肿瘤细胞系作用的研究

 目的 研究中药复方”冬夏丸“体外对6 株人肿瘤细胞系的作用。方法 分别用微量板染色法和流式细胞术测定肿瘤细胞的生长和细胞周期分布。结果 中药复方”冬夏丸“对6 株人肿瘤细胞均有显着的生长抑制效应,抑制率均随药物浓度的增加而增高;多数细胞系的半数抑制浓度（IC50） 相近;药物使鼻咽癌细胞G2 期增加并可诱导细胞凋亡。结论 中药复方”冬夏丸“体外对包括NPC在内的多种肿瘤细胞均有显着的生长抑制作用。     

细胞增殖周期失控与胃癌

 肿瘤的恶性增生从生物学角度看,主要表现在两个方面：一是肿瘤细胞的“不灭性”,即细胞凋亡障碍;二是细胞增殖失控,程序发生紊乱,致使增殖速度超常加快。这两方面均已成为肿瘤发生发展研究的热点。     

甘露糖抗肿瘤作用的研究进展

“Warburg效应”是肿瘤细胞重要的代谢特征之一,肿瘤细胞在氧气充足的条件下仍进行糖酵解,亦称“有氧糖酵解”。愈来愈多的研究表明肿瘤是一种代谢性疾病。因此探索肿瘤代谢变化及机制,以及靶向肿瘤代谢的肿瘤治疗成为近年来肿瘤研究的热点。目前基于肿瘤代谢的一些治疗方法（如生酮疗法、大剂量维生素C等）逐步引起基础研究和临床研究工作者的重视。最近有研究报导,甘露糖可以抑制肿瘤生长、增加阿霉素抗癌效果和延长荷瘤小鼠生存期。其主要作用机制是干扰葡萄糖代谢、促进肿瘤细胞凋亡以及增强化疗药物顺铂和阿霉素的抗肿瘤作用。此外,甘露糖还有调节免疫平衡等作用。甘露糖作为一种营养素,对人体健康无害,有望成为一种重要肿瘤代谢调节治疗的营养素,并且可与一线肿瘤治疗（化疗和放疗）配合来提高抗肿瘤治疗效果,具有重要的临床意义和应用前景。     

妇科常见肿瘤中细胞自噬现象的研究进展

目的:总结妇科常见肿瘤中细胞自噬现象的研究进展。方法:以"Autoph-agy"、"Beclin1"和"肿瘤"为关键词,检索2006-2010 PubMed及CNKI期刊全文数据库。纳入标准:1)细胞自噬与妇科肿瘤发生发展的关系;2)自噬相关基因Beclin1的结构及生物学特性;3)细胞自噬与妇科肿瘤的治疗。根据纳入标准分析28篇文献。结果:细胞自噬对肿瘤发生发展具有促进与抑制双重作用。卵巢癌、子宫内膜癌及宫颈癌等常见妇科恶性肿瘤组织中都存在自噬活性降低的现象。Beclin1在自噬活性缺失的妇科恶性肿瘤形成中起到了关键的作用,它可提高肿瘤细胞的自噬与凋亡能力并抑制肿瘤的恶性增殖。多种抗癌药物均可通过诱导细胞自噬而造成肿瘤细胞的死亡。细胞自噬及Beclin1基因为妇科肿瘤的治疗提供了一种新思路。结论:通过抑制具有细胞保护效应的自噬反应或促进可诱导凋亡的细胞自噬有可能成为妇科肿瘤生物治疗中的重要靶点。     

“免疫”核糖核酸在胃癌综合治疗中的作用

 据国内外有关报道,肿瘤致敏动物或荷瘤动物的脾脏、淋巴结提取的“免疫”核糖核酸（以下简称iR N A）,能逾越种间屏障传递抗肿瘤免疫反应^1～4.这为i RNA的肿瘤临床应用提供了实验依据.     

高迁移率族蛋白B1在肿瘤发生发展中的作用

高迁移率族蛋白B1（high mobility group box 1, HMGB1）是一种非组蛋白细胞核蛋白,属于损伤相关分子模式（DAMPs）中的一员,在多种肿瘤组织中高表达。可增强肿瘤细胞的增殖、侵袭和转移,促进肿瘤的发生发展;也可增强免疫反应,诱导肿瘤细胞凋亡,抑制肿瘤的发生发展;提示HMGB1在肿瘤中扮演着“双刃剑”的角色。这主要与HMGB1的定位和翻译后修饰有密切关系。本文就与肿瘤发生发展相关的HMGB1结构、翻译后修饰、定位、功能及目前HMGB1在各个肿瘤中概况作一综述。     

肿瘤坏死因子相关凋亡诱导配体及其受体与肝癌

肿瘤坏死因子相关凋亡诱导配体(TRAIL)及受体能在肝癌细胞中特异性地表达,并通过死亡受体特异性地诱导肿瘤细胞凋亡;TRAIL联合放疗、化疗能有效地克服肿瘤细胞的TRAIL耐受,促进肿瘤细胞凋亡,同时TRAIL的基因治疗在抗肿瘤临床治疗上已得到广泛的应用.     

胃癌的“免疫”核糖核酸治疗

 本文报告对42例失去根治性机会的胃癌患者施行姑息性胃次全切除术,20例术后给予“免疫”核糖核酸免疫治疗,22例术后不加免疫治疗作为对照。治疗组和对照组的五年生存率为55%和22.7%。两组患者的平均生存时间为45.15个月和34.31个月,免疫治疗后各项免疫指标均有增加。用“免疫”核糖核酸治疗后,未发现有任何毒性或其他不良反应。认为用同种“免疫”核糖核酸辅助治疗胃癌术后患者有一定的临床价值。     

单克隆抗体与肿瘤细胞凋亡

单克隆抗体町通过多种作用机制治疗肿瘤,其中诱导肿瘤细胞凋亡是主要机制之一。不同的单克隆抗体可通过3种途径诱导肿瘤细胞凋亡：通过阻断生长因子及其受体信号传导途径影响肿瘤细胞的存活和生长,同时增强联合治疗中化疗或放疗的作用;通过使相应的抗原交联启动细胞凋亡途径;通过直接作用于死亡受体导致细胞凋亡。     

单克隆抗体与肿瘤细胞凋亡

单克隆抗体可通过多种作用机制治疗肿瘤,其中诱导肿瘤细胞凋亡是主要机制之一。不同的单克隆抗体可通过3种途径诱导肿瘤细胞凋亡:通过阻断生长因子及其受体信号传导途径影响肿瘤细胞的存活和生长,同时增强联合治疗中化疗或放疗的作用;通过使相应的抗原交联启动细胞凋亡途径;通过直接作用于死亡受体导致细胞凋亡。     

The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma

Interleukin‐33 (IL‐33), an alarmin released during tissue injury, facilitates the development of cholangiocarcinoma (CCA) in a murine model. However, it is unclear whether IL‐33 is associated with human CCA. The aim of this study was to support the following hypothesis: IL‐33 is released during hepatectomy for CCA, subsequently facilitating the development of subclinical CCA and eventually leading to recurrent disease. IL‐33 expression was assessed in various samples from both humans and mice including resected liver and paired plasma samples collected at hepatectomy and after surgery, and its influences on recurrent disease and patient prognosis were determined. Homogenized human liver samples with high or low IL‐33 expression were added to the culture medium of human CCA cells, and the changes in proliferation and migration were evaluated. To examine the effects of inhibiting the IL‐33 release induced by hepatectomy, syngraft transplantation of murine CCA cells was performed in C57BL/6J mice with or without IL‐33 blockade. The amount of IL‐33 released into the plasma during hepatectomy correlated with the background liver expression. High expression of IL‐33 in the liver was an independent risk factor for recurrence. Homogenized liver tissue strongly expressing IL‐33 increased both the proliferation and migration of tumor cells. Mice who underwent hepatectomy exhibited CCA progression in the remnant liver, whereas blockade of IL‐33 during hepatectomy inhibited tumor progression. Thus, we concluded that surgery for CCA with curative intent paradoxically induced IL‐33 release, which facilitated CCA recurrence, and anti–IL‐33 therapy during hepatectomy might reduce the risk of CCA recurrence.     

miR‐200a/b/‐429 downregulation is a candidate biomarker of tumor radioresistance and independent of hypoxia in locally advanced cervical cancer

Many patients with locally advanced cervical cancer experience recurrence within the radiation field after chemoradiotherapy. Biomarkers of tumor radioresistance are required to identify patients in need of intensified treatment. Here, the biomarker potential of miR‐200 family members was investigated in this disease. Also, involvement of tumor hypoxia in the radioresistance mechanism was determined, using a previously defined 6‐gene hypoxia classifier. miR‐200 expression was measured in pretreatment tumor biopsies of an explorative cohort (n = 90) and validation cohort 1 (n = 110) by RNA sequencing. Publicly available miR‐200 data of 79 patients were included for the validation of prognostic significance. A score based on expression of the miR‐200a/b/‐429 (miR‐200a, miR‐200b, and miR‐429) cluster showed prognostic significance in all cohorts. The score was significant in multivariate analysis of central pelvic recurrence. No association with distant recurrence or hypoxia status was found. Potential miRNA target genes were identified from gene expression profiles and showed enrichment of genes in extracellular matrix organization and cell adhesion. miR‐200a/b/‐429 overexpression had a pronounced radiosensitizing effect in tumor xenografts, whereas the effect was minor in vitro. In conclusion, miR‐200a/b/‐429 downregulation is a candidate biomarker of central pelvic recurrence and seems to predict cell adhesion‐mediated tumor radioresistance independent of clinical markers and hypoxia.     

Bcl-2、miR-451和Th17细胞在食管癌中的诊断价值及其与复发的关系

目的 探讨Bcl-2、miR-451、Th17细胞在食管癌中的诊断价值及其与复发的关系.方法 选取101例食管癌患者作为研究组,95例健康体检者作为对照组.分析两组临床病理特征与各外周血指标水平之间的相关性,ROC曲线分析各外周血指标诊断价值,多元线性回归分析各指标与肿瘤复发的关系.结果 研究组外周血Bcl-2、miR...     

Recurrence-free survival after radiofrequency ablation of hepatocellular carcinoma. A registry report of the impact of risk factors on outcome

BACKGROUND: Despite the high complete necrosis rate of radiofrequency ablation (RFA), tumor recurrence, either local tumor recurrence or new tumor formation, remains a significant problem. Purpose of this study is to evaluate the pattern and risk factors for intrahepatic recurrence after percutaneous RFA for hepatocellular carcinoma (HCC). METHODS: We studied 40 patients with 48 HCCs (< or = 3.5 cm) who were treated with percutaneous RFA. The mean follow-up period was 24.1 +/- 15.7 months. We evaluated the cumulative disease-free survival of overall intrahepatic recurrence, local tumor progression (LTP) and intrahepatic distant recurrence (IDR). Thirty host, tumoral and therapeutic risk factors were reviewed for significant tie-in correlation with recurrence: age; gender; whether RFA was the initial treatment for HCC or not; severity of liver disease; cause of liver cirrhosis; contact of tumor to major hepatic vessels and liver capsule; degree of approximation of tumor to the liver hilum; ablation time; degree of benign pre-ablational enhancement; sufficient safety margin; tumor multinodularity; tumor histological differentiation; tumor segmental location; maximum tumor diameter; degree of tumor pre-ablational enhancement at arterial phase CT, MRI or CT-angiography; and laboratory markers pre- and post-ablation (AFP, PIVKA II, TP, AST, ALT, ALP and TB). RESULTS: The incidence of overall recurrence, LTP and IDR was 65, 23 and 52.5%, respectively. The cumulative disease-free survival rates were 54.6, 74.8 and 78.3% at 1 year, 27.3, 71.9 and 46.3% at 2 years and 20, 71.9 and 29.4 at 3 years, respectively. Univariate and multivariate analysis showed that the significant risk factors for LTP were: tumor size > or = 2.3 cm, insufficient safety margin, multinodular tumor, tumors located at segments 8 and 5, and patient's age > 65 years (P < 0.05). No significant risk factor relationship for IDR could be detected. CONCLUSION: Our results would have clinical implications for advance warning and appropriate management of patients scheduled for RFA. Patients at risk of LTP should be closely monitored in the first year. Furthermore, regular long-term surveillance is essential for early detection and eradication of IDR.     

TTI1 promotes non‐small‐cell lung cancer progression by regulating the mTOR signaling pathway

The role of TELO2‐interacting protein 1 (TTI1) in the progression of several types of cancer has been reported recently. The aim of this study was to estimate the expression and potential value of TTI1 in non‐small‐cell lung cancer (NSCLC) patients. The expression of TTI1 and its prognostic value in NSCLC from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were analyzed. To verify the bioinformatics findings, a tissue microarray containing 160 NSCLC and paired peritumoral tissues from NSCLC patients was analyzed by immunohistochemistry for TTI1. Subsequently, the roles of TTI1 in NSCLC cells were investigated in vivo by establishing xenograft models in nude mice and in vitro by transwell, CCK‐8, wound healing, and colony formation assays. In addition, quantitative real‐time polymerase chain reaction and western blot were applied to explore the underlying mechanism by which TTI1 promotes tumor progression. Finally, the relationship between TTI1 and Ki67 expression level in NSCLC was probed, and Kaplan–Meier and Cox analyses were performed to assess the prognostic merit of TTI1 and Ki67 in NSCLC patients. We found that the expression of TTI1 was significantly upregulated in NSCLC tissues compared to paired peritumoral tissues, which coincides with the bioinformatics findings from the TCGA and GEO databases. TTI1 was highly expressed in NSCLC patients with large tumors, advanced tumor stage, and lymphatic metastasis. In addition, the prognostic analysis identified TTI1 as an independent indication for poor prognosis of NSCLC patients. In vitro, upregulation of TTI1 in NSCLC cells could facilitate cell invasion, metastasis, viability, and proliferation. Mechanistically, our study verified that TTI1 could regulate mTOR activity, which has a pivotal role in human cancer. Consistently, the expressions of TTI1 and Ki67 had a positive relationship in NSCLC cells and tissues. Notably, patients with overexpression of TTI1 or Ki67 had a shorter overall survival rate and a higher disease‐free survival rate compared to patients with low expression of TTI1 or Ki67, and the combination of TTI1 and Ki67 was an independent parameter predicting the prognosis and recurrence of NSCLC patients. We conclude that TTI1 promotes NSCLC cell proliferation, metastasis, and invasion by regulating mTOR activity, and the combination of TTI1 and Ki67 is a valuable molecular biomarker for the survival and recurrence of NSCLC patients.     

Prognostic impact of circulating tumor cells detected with the microfluidic “universal CTC‐chip” for primary lung cancer

Detecting rare circulating tumor cells (CTCs) in the bloodstream is extremely challenging. We had previously developed a novel polymeric microfluidic device, “CTC‐chip,” for capturing CTCs and have shown high capture efficiency in lung cancer cell lines by conjugating Abs against epithelial cell adhesion molecules (EpCAM). This study aimed to optimize the EpCAM‐chip and clarify the prognostic impact of CTCs in lung cancer patients. Of 123 patients with pathologically proven lung cancer, both progression‐free survival (P = .037) and cancer‐specific survival (P = .0041) were predominantly poor when CTCs were detected before treatment. After classification into surgical and chemotherapy groups, progression‐free survival was worse in CTC‐positive patients in both groups (surgery, P = .115; chemotherapy, P = .012), indicating that the detection of baseline CTCs is a risk factor for recurrence and progression. Furthermore, we recovered captured CTCs using micromanipulators and undertook mutation analysis using PCR. Thus, the EpCAM‐chip is a highly sensitive system for detecting CTCs that contributes to the prediction of recurrence and progression and enables genetic analysis of captured CTCs, which could open new diagnostic, therapeutic, and prognostic options for lung cancer patients.     

The ELEANOR noncoding RNA expression contributes to cancer dormancy and predicts late recurrence of estrogen receptor‐positive breast cancer

The recurrence risk of estrogen receptor (ER)‐positive breast cancer remains high for a long period of time, unlike other types of cancer. Late recurrence reflects the ability of cancer cells to remain dormant through various events, including cancer stemness acquisition, but the detailed mechanism is unknown. ESR1 locus enhancing and activating noncoding RNAs (ELEANORS) are a cluster of nuclear noncoding RNAs originally identified in a recurrent breast cancer cell model. Although their functions as chromatin regulators in vitro are well characterized, their roles in vivo remain elusive. In this study, we evaluated the clinicopathologic features of ELEANORS, using primary and corresponding metastatic breast cancer tissues. The ELEANOR expression was restricted to ER‐positive cases and well‐correlated with the ER and progesterone receptor expression levels, especially at the metastatic sites. ELEANORS were detected in both primary and metastatic tumors (32% and 29%, respectively), and frequently in postmenopausal cases. Interestingly, after surgery, patients with ELEANOR‐positive primary tumors showed increased relapse rates after, but not within, 5 years. Multivariate analysis showed that ELEANORS are an independent recurrence risk factor. Consistently, analyses with cell lines, mouse xenografts, and patient tissues revealed that ELEANORS upregulate a breast cancer stemness gene, CD44, and maintain the cancer stem cell population, which could facilitate tumor dormancy. Our findings highlight a new role of nuclear long noncoding RNAs and their clinical potential as predictive biomarkers and therapeutic targets for late recurrence of ER‐positive breast cancer.     

Scavenging of reactive oxygen species leads to diminished peritoneal tumor recurrence

Previously, we demonstrated that RBCs inhibit the recurrence of perioperatively spilled tumor cells. The aim of this study was to identify on which RBC component(s) the inhibitory effect is based. By using a cell-seeding model in rats, the effect of RBC-related antioxidant scavengers [hemoglobin, catalase, and superoxide dismutase (SOD)] on peritoneal tumor recurrence was investigated. i.p. injection of hemoglobin caused 45% more tumor load (P < 0.0001). At least 40% inhibition of tumor recurrence was achieved with the use of catalase or SOD (P < 0.05). Combining SOD and catalase did not lead to additional inhibition of tumor recurrence. Inhibition of the overwhelming oxidative potential after surgical peritoneal trauma with the use of scavengers may lead to interesting new approaches for diminishing peritoneal tumor recurrence.     

Chemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse

Cervical cancer therapy is still a major clinical challenge, as patients substantially differ in their response to standard treatments, including chemoradiotherapy (CRT). During cervical carcinogenesis, T‐helper (Th)‐17 cells accumulate in the peripheral blood and tumor tissues of cancer patients and are associated with poor prognosis. In this prospective study, we find increased Th17 frequencies in the blood of patients after chemoradiotherapy and a post‐therapeutic ratio of Th17/CD4⁺ T cells > 8% was associated with early recurrence. Furthermore, Th17 cells promote resistance of cervical cancer cells toward CRT, which was dependent on the AKT signaling pathway. Consistently, patients with high Th17 frequencies in pretherapeutic biopsies exhibit lower response to primary CRT. This work reveals a key role of Th17 cells in CRT resistance and elevated Th17 frequencies in the blood after CRT correspond with early recurrence. Our results may help to explain individual treatment responses of cervical cancer patients and suggest evaluation of Th17 cells as a novel predictive biomarker for chemoradiotherapy responses and as a potential target for immunotherapy in cervical cancer.     

Postoperative Recurrence and Survival After Segmentectomy for Clinical Stage 0 or IA Lung Cancer

BackgroundAlthough radical segmentectomy is an accepted treatment option for small-sized lung cancer, the outcomes remain unclear. The present study aimed to elucidate recurrence patterns and to identify predictors of time to recurrence after intentional segmentectomy for early lung cancer.Patients and MethodsProspectively collected data of 166 patients who could tolerate lobectomy and underwent intentional segmentectomy for clinical stage 0 or IA non–small-cell lung cancer between 2007 and 2016 were retrospectively analyzed. Surgical indication for intentional segmentectomy was clinical stage 0 or IA ground glass opacity-dominant tumor ≤ 3 cm or solid-dominant tumor ≤ 2 cm on high-resolution computed tomography.ResultsThe median follow-up duration was 48.8 months, during which 6 (3.6%) patients developed recurrences. The 5-year recurrence-free survival and 5-year overall survival rates were 93.1% (95% confidence interval [CI], 87.9%-96.1%) and 93.5% (95% CI, 87.7%-96.4%), respectively. Two (1.2%) patients who developed local-only recurrences subsequently underwent completion lobectomy; no cancer-related deaths were seen for these patients. In multivariable analysis, consolidation to maximum tumor diameter (C/T) ratio (hazard ratio, 1.07; 95% CI, 1.01-1.22; P = .02) was an independent predictive factor for time to recurrence. All 6 patients with recurrence had a tumor with a C/T ratio of 86% or higher.ConclusionsBased on these findings, favorable survival is expected after intentional segmentectomy for selected patients with clinical stage 0 or IA non–small-cell lung cancer. Patients with a higher C/T ratio tumor appear to be at higher risk of recurrence after intentional segmentectomy.