直肠癌术后肺转移72例的临床分析

目的：探讨直肠癌根治术后肺转移的治疗效果和影响预后的因素。方法：回顾性分析1978～2008年间的直肠癌根治术后发生单纯性肺转移的72例病例资料。结果：自原发灶切除术后全组病例中位生存时间34个月,行转移灶的切除手术23例,中位生存49个月;其余49例行非手术治疗,中位生存33个月;其中转移瘤大于3个组中位生存时间28个月,转移瘤小于等于3个组中位生存时间41个月。手术患者和转移灶个数少的患者的总生存率较大,总生存率可能和是否手术、转移灶的个数有关,但尚未发现年龄、性别、原发灶病理类型、分期、转移灶大小对生存率有明显影响。结论：直肠癌肺转移灶的手术治疗是安全、有效的。手术及转移灶个数可影响患者生存率。     

Adjuvant immunotherapy with intrapleuralStreptococcus pyogenes (OK-432) in lung cancer patients after resection

A prospective randomized study to evaluate the effect of adjuvant intrapleural OK-432 immunotherapy after resection of lung tumor was conducted in 93 patients with primary lung cancer. Among them, 46 patients had had intrapleural OK-432 injection, 47 had not. In the meantime, serial measurements of serum immunosuppressive acidic protein, of serum interleukin-2 receptor and of the sub-population of the peripheral blood cells and lymphocytes were performed in all these patients. Patient characteristics in these two groups (sex, age, histological type, pathological stage, type of operation, and performance status) were compatible. The results showed that adjuvant intrapleural OK-432 injection after resection had no beneficial effect on a patient's survival time. Patients who received intrapleural OK-432, had an increase in blood leukocytes, granulocytes and monocytes and serum immunosuppressive acidic protein level. But the cell numbers of total T cells, suppressor/cytoxic cells, helper/inducer cells and natural killer cells of peripheral blood were decreased in the OK-432 positive group. Over half of the patients had transient 1- or 2-day febrile reactions after intrapleural OK-432 injection. It was concluded that neither clinical observation nor immunological monitoring of peripheral blood could demonstrate a beneficial effect from intrapleural OK-432 immunotherapy after complete resection of the tumor.     

Preoperative albumin-to-globulin ratio predicts survival in patients with non-small-cell lung cancer after surgery

The prognostic value of the preoperative albumin-to-globulin ratio (AGR) has not been investigated in non-small-cell lung cancer (NSCLC). Therefore, we aimed to assess the clinical applicability of the preoperative AGR to predict the prognosis in patients with NSCLC. We retrospectively enrolled 545 patients with stage I/II/III NSCLC who underwent surgery at our institution. The cutoff value for preoperative AGR was calculated by using a receiver operating characteristic curve analysis. A low AGR was associated with several clinicopathological variables related to tumor progression. In the multivariate analyses, the preoperative AGR was identified as an independent prognostic factor for disease-free survival (DFS; P = 0.003) and overall survival (OS; P = 0.005). For patients with stage II and III with a preoperative AGR ≤ 1.43, the surgery plus chemotherapy group had a significantly longer DFS and OS than the surgery alone group (P = 0.002 and P = 0.001, respectively); however, a significant difference in DFS and OS between these two groups was not observed in patients with stage II and III with an AGR > 1.43 (P = 0.808 and P = 0.842, respectively). The preoperative AGR is an independent, significant predictor of DFS and OS in patients with NSCLC. Our results also demonstrate that the preoperative AGR might be a predictive marker of the therapeutic effect of postoperative chemotherapy in patients with stage II and III NSCLC.     

芹菜多糖抑制小鼠肺癌的作用研究*

目的:探讨芹菜多糖抗肺癌的作用及机制。方法:提取纯化芹菜多糖,通过红外光谱和凝胶渗透色谱法对其进行鉴定;每只小鼠腹股沟皮下注射2×10⁷个Lewis肺癌细胞,建立肺癌C57BL/6小鼠模型,随机分为5组,每组10只。两天后,分别0、25、50、75、100 mg/kg芹菜多糖灌胃荷瘤小鼠10 d,流式和qPCR法分析小鼠外周血CD4⁺、CD8⁺淋巴细胞和脾淋巴细胞因子IL-2、IFN-γ与IL-4,并取肿瘤组织拍照和称重。结果:本实验所提取的芹菜多糖纯度为82%,鉴定为不均一的多糖,分子量为1.17×10³ kD;芹菜多糖灌胃小鼠可显著抑制肺癌的生长(P＜0.01),75 mg / kg治疗10 d后,可提高小鼠外周血CD4⁺和CD8⁺淋巴细胞的百分比(P ＜0.01),并明显增加50 mg / kg以上治疗组的脾淋巴细胞IL-2、IFN-γ和IL-4的转录水平(P ＜0.01)。结论:芹菜多糖可通过增强机体免疫,尤其是细胞免疫而发挥抗肺癌的作用。     

TN-C 在小细胞肺癌中的表达及STAT3 对TN-C 表达的影响

目的：探讨小细胞肺癌(SCLC)组织和小细胞肺癌细胞(H446)中肌糖蛋白-C(TN-C)的表达及STAT3 对TN-C表达的影响。 方法：应用免疫组化法检测58 例小细胞肺癌和17 例癌旁正常组织中TN-C 的表达水平,应用RT-PCR和Western blotting 法检测 STAT-siRNA和STAT3 过表达的H446 细胞中TN-C 的表达水平。结果：(1)小细胞肺癌组织中TN-C 的表达水平显著高于癌旁正 常组织(P<0.05);(2)在H446细胞中,TN-C 和STAT3 均呈现高表达;(3)STAT3-siRNA 处理的H446 细胞中STAT3 和TN-C 的表 达均显著降低(P<0.05),而STAT3 过表达的H446 细胞中STAT3 和TN-C 的表达均显著上调(P<0.05)。结论：TN-C 在小细胞肺癌 中的表达上调,可能受到STAT3 的调控。     

TN-C在小细胞肺癌中的表达及STAT3对TN-C表达的影响

目的：探讨小细胞肺癌（SCLC）组织和小细胞肺癌细胞（H446）中肌糖蛋白-C（TN-C）的表达及STAT3对TN-C表达的影响。方法：应用免疫组化法检测58例小细胞肺癌和17例癌旁正常组织中TN-C的表达水平,应用RT-PCR和Western blotting法检测STAT-siRNA和STAT3过表达的H446细胞中TN-C的表达水平。结果：（1）小细胞肺癌组织中TN-C的表达水平显著高于癌旁正常组织（P〈0.05）;（2）在H446细胞中,TN-C和STAT3均呈现高表达;（3）STAT3-siRNA处理的H446细胞中STAT3和TN-C的表达均显著降低（P〈0.05）,而STAT3过表达的H446细胞中STAT3和TN-C的表达均显著上调（P〈0.05）。结论：TN-C在小细胞肺癌中的表达上调,可能受到STAT3的调控。     

Heterogeneity of lipidomic profiles among lung cancer subtypes of patients

Lung cancer is a leading cause of cancer‐related deaths with an increasing incidence and poor prognoses. To further understand the regulatory mechanisms of lipidomic profiles in lung cancer subtypes, we measure the profiles of plasma lipidome between health and patients with lung cancer or among patients with squamous cell carcinomas, adenocarcinoma or small cell lung cancer and to correct lipidomic and genomic profiles of lipid‐associated enzymes and proteins by integrating the data of large‐scale genome screening. Our studies demonstrated that circulating levels of PS and lysoPS significantly increased, while lysoPE and PE decreased in patients with lung cancer. Our data indicate that lung cancer‐specific and subtype‐specific lipidomics in the circulation are important to understand mechanisms of systemic metabolisms and identify diagnostic biomarkers and therapeutic targets. The carbon atoms, dual bonds or isomerism in the lipid molecule may play important roles in lung cancer cell differentiations and development. This is the first try to integrate lipidomic data with lipid protein‐associated genomic expression among lung cancer subtypes as the part of clinical trans‐omics. We found that a large number of lipid protein‐associated genes significantly change among cancer subtypes, with correlations with altered species and spatial structures of lipid metabolites.     

The effect of silica exposure on the risk of lung cancer: A meta-analysis

Lung cancer is an incurable disease with an increased mortality rate caused by the inhalation of dust-containing crystalline silica particles. Silica exposure is one of the most important occupational hazards in the world. Whether the association between silica exposure and lung cancer is because of the fibrotic process or to the effect of respirable silica itself is unclear. The International Agency for Research on Cancer (IARC) classified silica as a human lung carcinogen. The opinion of lung cancer is a question that has been addressed in this review. Three electronic databases, including MEDLINE, Scopus, and Web of Science, were used to search for relevant literature from 2000 to 2022. To evaluate the relationship between exposure to silica and developing lung cancer, we performed a meta-analysis using the random-effects model. For each study, the overall odds ratio (OR), relative risk (RR) with 95% confidence intervals (CI), and p values were calculated. An extensive database search resulted in the selection of 20 (case‒control and nested case‒control studies were selected) out of 527 studies. Among the 20 selected studies, 7 studies showed a significant association between silica exposure and an increased risk of lung cancer. Further analysis showed that among the selected studies, six studies showed a significant correlation between combined exposure to silica and smoking with an increased risk of lung cancer. The data from the present study showed that smoking habits increased the impact of silica exposure on the initiation of lung carcinogenesis in exposed workers.     

Factors affecting survival after palliative radiotherapy in patients with lung cancer

BackgroundLung cancer is the most common cancer worldwide. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to identify factors that play a major role in the survival of lung cancer patients treated with palliative radiotherapy.Materials and methodsWe retrospectively reviewed data of 280 lung cancer patients treated with palliative radiotherapy from January 2013 to December 2017. A multivariate analysis using the proportional hazards model of Cox was conducted. Also, Kaplan Meier curves were used to describe the distribution of survival times of the patients. The level of significance was set at 0.05.ResultsThe mean age at diagnosis was 65.6 years. About 77.5% of patients were male and 22.5% were female. In our cohort > 95% had stage 4 lung cancer. Most cases were adenocarcinomas (72.5%) and ECOG-PS 0–1 (80.4%). Different sites were submitted to palliative treatment: 120 brain metastases, 96 bone metastases, 53 lung tumour, 8 lymph nodes and 3 lung metastases. Brain as first site of palliative radiotherapy (HR: 1.553, 95% CI: 1.167–2.067, p = 0.003) and ECOG-PS 2–3 compared with ECOG-PS 0–1 (HR: 2.253, 95% CI: 1.546–3.283, p ≤ 0.001) were associated with increased likelihood of lung cancer death. Patients who received biological therapy had 70.7% (p ≤ 0.001) reduction in lung cancer death risk.ConclusionBrain as the first metastatic site treated with radiotherapy and ECOG-PS 2–3 are associated with increased lung cancer death. Biological therapy was associated with decreased death risk.     

Antitumor effect of miR-197 targeting in p53 wild-type lung cancer

Lung cancer is the leading cause of tumor-related death. The lack of effective treatments urges the development of new therapeutic approaches able to selectively kill cancer cells. The connection between aberrant microRNA (miRNA – miR) expression and tumor progression suggests a new strategy to fight cancer by interfering with miRNA function. In this regard, LNAs (locked nucleic acids) have proven to be very promising candidates for miRNA neutralization. Here, we employed an LNA-based anti-miR library in a functional screening to identify putative oncogenic miRNAs in non-small-cell lung cancer (NSCLC). By screening NIH-H460 and A549 cells, miR-197 was identified as a new functional oncomiR, whose downregulation induces p53-dependent lung cancer cell apoptosis and impairs the capacity to establish tumor xenografts in immunodeficient mice. We further identified the two BH3-only proteins NOXA and BMF as new miR-197 targets responsible for induction of apoptosis in p53 wild-type cells, delineating miR-197 as a key survival factor in NSCLC. Thus, we propose the inhibition of miR-197 as a novel therapeutic approach against lung cancer.     

MiRNA调控非小细胞肺癌转移的研究进展

微小RNA是内源性的非编码小RNA分子,通过与靶mRNA的结合在转录后水平调控基因的表达,从而参与众多生命活动的调控。NSCLC是严重威胁人类健康的恶性肿瘤,侵袭转移是其主要特征,也是其治疗失败和死亡的主要原因。miRNA可以通过促进上皮-间质转化、金属基质蛋白酶表达,以及血管生成来促进NSCLC转移,而且miRNA在调节肺癌干细胞特性中也发挥着重要作用。转移相关的miRNA已成为肺癌靶向治疗的新靶点。     

Drug-induced cell cycle perturbation in chemotherapy of patients with non-small cell lung cancer

To observe in vivo cell cycle perturbation in the chemotherapy of lung cancer, tumour cell kinetics during the first course of chemotherapy were measured in seven patients with histologically-verified non-small cell lung cancer. The tumour cells were aspirated from six lymph nodes and one subcutaneous nodule both prior to treatment and twice weekly after the administration of chemotherapeutic agents. The nuclear DNA content of aspirated tumour cells was measured with a scanning microdensitometer at a wavelength of 550 nm after the modified Feulgen reaction. The cell population in cell cycle was estimated with a cumulated percentage scale. Marked cell cycle perturbation occurred within one week after initiation of chemotherapy. There was a decrease in the G1 cell population, from 70.6 +/- 9.1% to 26.1 +/- 11.4%, and a corresponding increase of cells in G2-M phase, from 21.4 +/- 8.7% to 63.7 +/- 10.0%. The proportion of cells in S phase was slightly increased from 8.0 +/- 1.5% to 10.1 +/- 3.2% during this period. The degree of cell cycle changes was unrelated to the clinical response to chemotherapy.     

小细胞肺癌患者外周血淋巴细胞亚群分析

目的 探究化疗对小细胞肺癌(small cell lung cancer,SCLC)患者免疫功能的影响。 方法 选择2013年1月到2018年12月我院收治的95例小细胞肺癌患者为研究对象。患者第一周期、第二周期化疗前采用流式细胞术检测患者外周血淋巴细胞亚群水平,分别按照不同疗效及不同化疗方案对患者外周血淋巴细胞亚群进行比较。 结果 (1)化疗后,95例患者CD3+、CD4+、CD8+细胞平均值增加,CD19+、γδT细胞平均值减少,差异均有统计学意义(均P+、CD8+细胞平均值增加,CD19+细胞减少,差异有统计学意义(均P0.05)。(3)依托泊苷联合顺铂(EP)方案组化疗后患者CD3+、CD8+细胞平均值增多,CD19+细胞减少,差异均有统计学意义(均P0.05)。 结论 化疗可以调节小细胞肺癌患者的免疫功能,增强细胞免疫,降低体液免疫,其中EC方案对患者细胞免疫的增强作用较为显著。     

Birth in winter can reduce the risk of lung cancer: A retrospective study of the birth season of patients with lung cancer in Beijing area,China

The season of birth is an important risk factor for several diseases. We explored the relationship between birth season and lung cancer. In this population-based retrospective study, we focused on patients with lung cancer who had registered at the Beijing Institute for Cancer Research from 2003 to 2012. In total, 33,025 patients were divided into five subgroups based on their histologic classification, and these five subgroups were compared with the general population (i.e., the permanent resident population of Beijing in 2013). A binary logistic regression method with sex and age as control factors was used to evaluate the relationship between birth season and lung cancer; P < 0.01 was statistically significant. Taking winter as a reference in our analysis of the relationship between season of birth and lung cancer, we found that people who were born in other seasons had a higher probability of developing lung cancer (spring: odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.03–1.09; summer: OR = 1.07, 95% CI = 1.04–1.10; autumn: OR = 1.06, 95% CI = 1.03–1.09) (P < 0.01). Among the five subgroups, persons with squamous cell carcinoma who were born in summer were more likely to develop lung cancer than those who were born in winter (OR = 1.09, 95% CI = 1.02–1.15, P = 0.006). The other subgroups showed no correlation with season of birth (P > 0.01). This study demonstrates that for people born in winter, the risks of developing lung cancer and squamous cell carcinoma are comparatively lower than those for people born in other seasons. Differences in immune function and the maternal nutrition status during pregnancy of people born in different seasons may explain this finding.     

Effect of lung resection on blood lactate threshold in lung cancer patients

We studied the effect of a decrease in vital capacity (VC) on the blood lactate threshold detected during exercise in 16 preoperative (PRE) and 10 postoperative (POST) lung cancer patients who had undergone lobectomy or pneumonectomy. The PRE patients were selected on the basis of having normal preoperative pulmonary function. The POST patients were selected on the basis of having normal preoperative pulmonary function and a postoperative VC of less than 80%. The oxygen consumption/body surface area at a 2.2 m.mol.l-1 arterial lactate concentration (VO2/BSA at La-2.2) was adopted as the blood lactate threshold. VC/BSA in the POST group significantly correlated with VO2/BSA at La-2.2 (r = 0.85, P less than 0.01), but not in the PRE group. SaO2 at La-2.2 was 95.4 +/- 1.5% in the PRE group and 95.2 +/- 1.3% in the POST group. SaO2 at La-2.2 did not correlated with VC/BSA in either group. The hemoglobin concentration (Hb) in the arterial blood correlated significantly with VC/BSA in the POST group (r = 0.65, P less than 0.05) but not in the PRE group. These results indicate that VO2/BSA at La-2.2 was restricted by VC in patients with restrictive pulmonary function disorder. Of the three elements of oxygen delivery, Hb was a limiting factor for VO2/BSA at La-2.2 but SaO2 was not. Cardiac output, which was not measured in our study, was speculated to be another limiting factor for VO2/BSA at La-2.2.     

Combined effect of GSTM1, GSTT1 and GSTP1 polymorphisms on histological subtypes of lung cancer

Genetic polymorphisms are natural genetic variations in the gene sequence that occur at a frequency of >1% in the population. This genetic variability (polymorphisms) can be a factor in cancer risk. The functional polymorphisms in GST genes play an important role in susceptibility to lung cancer. In our previous study, we reported that the combination of certain genotypes of GSTM1, GSTT1 and CYP1A1 is associated with lung cancer. The study has been extended to investigate the potential role of polymorphism in GSTP1 alone or in combination with the status of GSTM1 and GSTT1 genes in the likelihood of development of lung cancer. A total of 302 subjects (151 cases and 151 controls) were evaluated. Using a case–control design, individuals were genotyped for GSTs using multiplex polymerase chain reaction and restriction fragment length polymorphism techniques. The data obtained were analyzed using multiple logistic regression. The combined ‘at risk’ genotypes of GSTM1 null and GSTT1 null in comparison with ‘wild-type’ genotypes seems to be associated with a greater risk of lung cancer, but the results are not significant (odds ratio (OR) 2.0, 95% confidence interval (CI) 0.68–5.96) and for squamous cell carcinoma (SqCC) it was 1.6-fold (OR 1.6, 95% CI 0.49–5.68). In summary, our case–control study of lung cancer revealed that the effect of these polymorphisms is not very marked for different genotypic combinations of GSTP1, GSTM1 and GSTT1 in the context of developing lung cancer in a north Indian population. However, the increased risk was limited to SqCC, and was not found for other histological subtypes. Further analyses on this topic are needed.     

非小细胞肺癌患者肠道微生物特征分析

[目的]分析非小细胞肺癌患者与肺部良性病变患者肠道微生物的构成差异,探究特异肠道菌群对非小细胞肺癌发生发展的影响.[方法]收集63例患者粪便样本,非小细胞肺癌患者39例,其中肺腺癌(ADC) 32例,肺鳞癌(SCC)7例,肺部良性病变患者24例,进行16S rDNA测序.[结果]毛螺菌属(Lachnospira)、瘤胃...     

Role of toll-like receptors in lung cancer

Abstract

Lung cancer is a leading cause of death world-wide and the long-term survival rate for patients with lung cancer is one of the lowest for any cancer. Toll-like receptors (TLRs), evolutionarily conserved innate, are expressed in a wide variety of tissues and cell types, and they play key role in the innate immune system. TLRs have been found to be expressed by some kinds of tumor cells. However, what is the biological function of TLRs on tumor cells and whether human lung cancer cells can express TLRs remain to be fully understood. This review was performed to sum up the role of TLRs in lung cancer.     

sFas levels increase in response to cisplatin-based chemotherapy in lung cancer patients

The Fas/Fas Ligand (FasL) system and survivin have counteracting roles in cell survival. Therefore, we explored the role of circulating soluble Fas (sFas) and the tissue levels of Fas and survivin with regard to response to chemotherapy in lung cancer patients. Serum samples from 52 lung cancer patients and 54 control subjects (19 benign lung disease and 35 healthy control subjects) were collected prior to and 24 and 48 h after chemotherapy. sFas was statistically significantly higher in the cancer group than that in the control groups (p < 0.001). Baseline (before chemotherapy) sFas values showed a statistically significant inverse correlation with overall survival (r = ?0.599, p < 0.001). There was a significant increase in serum sFas levels 24 h after treatment (p < 0.05). Contrarily, tissue levels of Fas and survivin were not changed following the chemotherapy (p > 0,05). In conclusion, increased sFas may be an indicator of poor outcome in lung cancer patients. However, cisplatin‐based chemotherapy may not be effective via neither the Fas/FasL system nor survivin pathway. Indeed, larger sample size is required for further evaluation. Copyright © 2010 John Wiley & Sons, Ltd.     

88例女性小细胞肺癌临床特征分析

目的了解女性小细胞肺癌的临床特征分布。方法收集2006年1月至2012年11月大连医科大学附属二院收治的341例小细胞肺癌女性患者88例的临床资料,分析患者在年龄、分期、就诊症状、体重下降、吸烟、家族史、肿瘤位置、治疗方式、疗效反应等方面的特征。结果 2006-2012年该院女性小细胞肺癌住院患者数呈上升趋势;女性患者平均患病年龄为（57.8±11.2）岁,小于同期男性患者（60.4±10.3）岁;女性〈65岁患者比例高于男性患者（73.9%vs 67.5%）,两者比较差异有统计学意义（P=0.018）;女性患者吸烟只有13.6%,远远低于男性患者吸烟比例（85.5%）,两者比较差异有统计学意义（P=0.000）;女性家族史、体重下降、就诊症状、肿瘤位置、分期、疗效以及治疗方式的选择均与男性无差别。在广泛期小细胞肺癌中观察到女性最常见的远处转移是肝转移（40.0%）,男性肝转移只占22.2%,两者比较差异有统计学意义（P=0.036）。结论女性小细胞肺癌数一直呈上升趋势;女性小细胞肺癌就诊的平均年龄小于男性患者;在中青年小细胞肺癌中女性常见;女性吸烟患者较少;相对于男性患者,女性更常见于肝转移。