恶性肿瘤与血栓形成研究进展

血栓形成是癌症患者最常见的并发症之一,也是仅次于癌症本身引起患者死亡的主要因素。癌症患者凝血系统的改变,将会对肿瘤的形成、转移等产生影响。本文通过介绍恶性肿瘤患者并发血栓形成的风险评估以及预防方法,总结恶性肿瘤血栓形成的危险因素及发生机制,探讨临床实践过程中恶性肿瘤血栓形成的风险评估方法和预防措施,为避免或减少血栓的发生提供参考。     

吸烟与血管钙化

吸烟是动脉粥样硬化的主要危险因素之一,然而吸烟与血管钙化(vascular calcification)之间的相关性尚未完全明确。越来越多证据表明吸烟可能是血管钙化的一个独立危险因素,其中尼古丁在血管钙化发生发展过程中的作用应得到重视和阐明。本文就吸烟与血管钙化的相关性及其机制研究进展简要作一综述,以期通过戒烟宣传防治血管钙化相关心血管疾病。     

吸烟对肺组织D4-GDI表达的影响及其与慢性阻塞性肺疾病相关性的蛋白质组学研究

慢性阻塞性肺疾病(COPD)是环境因素与遗传因素共同作用的结果,而吸烟是导致COPD发生的最主要危险因素,然而,吸烟导致COPD的机制及COPD的遗传易感机制目前尚未完全阐明．蛋白质组学研究方法具有高效和信息含量丰富的特点,为COPD研究提供了有力的帮助,被认为在COPD的研究领域具有广阔的前景．运用二维凝胶电泳和基质辅助激光解吸电离飞行时间质谱蛋白质组学研究方法结合生物信息学技术,对不吸烟者、非COPD吸烟者和吸烟COPD患者的肺组织进行蛋白质组比较,共鉴定出24种表达差异蛋白．研究发现,非COPD吸烟者肺组织ρ-GDP解离抑制因子2(D4-GDI)表达水平为不吸烟者的1.7倍,吸烟COPD患者肺组织D4-GDI表达水平接近非COPD吸烟者的2倍．通过免疫组织化学染色和Western-blotting检测对肺组织D4-GDI表达水平进行验证,获得了与蛋白质组学研究相一致的结果．结果首次说明：吸烟能够导致肺组织D4-GDI表达水平升高,D4-GDI参与了COPD的发病机制而且可能与COPD易感性相关．     

食物与癌

过去30多年,在癌症研究方面取得了重大进展。其中最重要的发现之一,是对环境在癌形成中的作用程度的认识。据估计,全部癌中有80％—90％是由环境因素(包括饮食和其他的生活习惯方面的因素)引起的。因此,大多数癌是能够预防的。不少研究者认为,饮食对癌的发生的影响可能比吸烟还要大。据专家们估计,癌症中有35％是由饮食引起的。生物学教师要尽一切努力教育学生,使他们懂得如何减少癌的危险。下面就饮食与癌的发生问题提出一些看法。     

饮酒、吸烟与冠状动脉病变程度的相关性研究

目的:探讨饮酒、吸烟与冠状动脉病变程度的相关性。方法:抽取行冠脉造影的男性患者(343例),排除患有高血压病、糖尿病、肝肾功能等异常的患者,根据患者是否吸烟、饮酒将其分为四组,吸烟+饮酒组(86例),吸烟+非饮酒组(135例),饮酒+非吸烟饮酒组(16例),非吸烟+非饮酒组(106例)。通过Gensini积分系统评价和比较各组冠脉病变的情况,分析评估冠心病的风险因素以及饮酒、吸烟与冠心病的关系。结果:吸烟+非饮酒组Gensini评分最高(33.89±31.14)分别与另外三组有统计学意义(P0.05)。饮酒+非吸烟组最低(9.31±10.88),分别与另外三组有统计学意义(P0.05)。单因素分析结果显示年龄、饮酒、TG、HDL-C是发生冠心病的危险因素,logistic回归分析结果显示饮酒是发生冠心病的保护因素,年龄与TG是发生冠心病的危险因素。结论:吸烟为冠状动脉病变高危因素,饮酒是发生冠心病的保护因素。     

伤寒带菌与胆囊癌形成

近年来,世界范围内伤寒发病人数有所上升,每年大约有2100万人感染,近5％感染者会发展成慢性带菌者.慢性带菌状态发展成胆结石的危险性很高,胆结石表面形成的生物膜有助于保持慢性带菌状态,进而可能发展成胆囊癌.胆囊癌比较少见,但在某些国家和地区发病率高,且女性胆结石和胆囊癌的发病率是男性的2倍多.慢性带菌状态不仅是胆囊癌发生的危险因素,也是其他癌症发生的危险因素.本文就伤寒带菌状态与生物膜和胆结石的形成及发展成胆囊癌的相关性研究进行综述.     

共济失调毛细血管扩张症致病基因与乳腺癌易感性

乳腺癌是与环境因素密切相关的肿瘤之一,致癌因素诱发的DNA损伤信号被传送到多个效应因子,最终导致细胞坏死和癌变。其中,共济失调性毛细血管扩张症致病基因(Ataxia-telangiectasia mutated,ATM)编码的ATM蛋白激酶是DNA损伤应答的主要调控因子,其通过磷酸化一系列下游底物来应对DNA损伤,这在抑制乳腺癌的发生发展中起到了重要的作用。ATM基因突变后,导致损伤DNA不能得到正确修复,最终加速了乳腺癌的转化和增殖。随着对ATM基因结构、功能及乳腺癌易感性机制研究的深入,ATM基因与乳腺癌易感性关系已引起广泛的重视。以下就ATM基因突变、多态性和甲基化等几个方面与乳腺癌易感性的关系进行了简要概述。     

炎性单核细胞促进乳腺癌转移的分子机制

癌症患者的最大威胁来自肿瘤的转移,若能控制肿瘤的转移,癌症对人类的最大威胁就会消除,也就是癌症可作为一种慢性疾病来治疗。如何控制癌症的转移?这成为癌症研究和治疗的中心问题。以前对肿瘤的转移研究主要集中在肿瘤细胞本身,现在看来这是不够的,目前已经把研究的目光转移到肿瘤的生态环境或微环境。人们已经知道肿瘤的发生和生长是由多种细胞、因子和外界因素协同作用而产生的,它生存在一个非常复杂的生态坏境(即     

氢分子在癌症防治中的应用进展

氢分子作为新型抗氧化剂,对多种由氧化应激和炎症引起的疾病具有良好的治疗效果。肿瘤发病机制复杂,预防和治疗难度大,一些恶性肿瘤的发生与慢性炎症和氧化应激相关,氢分子是否能够通过发挥抗炎症和抗氧化的作用预防癌症的发生并抑制肿瘤的发展得到广泛关注。现有研究表明,氢分子对多种肿瘤具有一定的预防和治疗作用,并能在肿瘤放化疗中起到减副增效的作用,提高患者生存质量。围绕氢分子在癌症预防和治疗方面的发展现状,综述了近年来氢分子在肿瘤研究方面的进展,并对未来的发展方向进行了展望,以期为氢分子在癌症防治中的应用提供参考。     

冠心病患者经皮冠状动脉介入治疗术后支架内再狭窄的相关危险因素分析

目的:探究冠心病(CHD)患者经皮冠状动脉介入治疗(PCI)术后支架内再狭窄(ISR)的相关危险因素。方法:选取2014年6月～2017年6月期间我院收治的行PCI的CHD患者200例为研究对象,术后随访一年再行冠脉造影检测,根据患者是否发生ISR分为观察组(38例,发生ISR)和对照组(162例,未发生ISR),收集并比较两组患者基线资料及生化指标,采用多因素logistic回归分析CHD患者PCI术后发生ISR的危险因素。结果:观察组吸烟、饮酒、高血压、糖尿病的人数占比、病程及支架直径均高于对照组,差异有统计学意义(P0.05)。观察组脂蛋白(a)[LP(a)]、纤维蛋白原(FIB)及尿酸(UA)水平显著高于对照组,总胆红素(TBIL)水平显著低于对照组,差异有统计学意义(P0.05)。多因素logistic回归分析显示,吸烟、糖尿病、支架直径(小)以及高水平LP(a)、低水平UA为CHD患者行PCI术后发生ISR的危险因素。结论:CHD患者行PCI术后发生ISR的危险因素有吸烟、糖尿病、支架直径以及高水平LP(a)、低水平UA,因此在PCI术中应尽可能选用较大的支架,同时戒烟、控制血糖有利于预防ISR的发生,定期检测血清LP(a)、UA水平变化,并采取有效的医疗与保健措施能够减少ISR的发生风险。     

Expression of p27Kip1 and bcl-2, cigarette smoking,and colorectal cancer risk

Although a positive association between cigarette smoking and colorectal adenoma development is consistently found, the association with colorectal cancer remains controversial. We evaluated the potential roles of p27^Kip1 and bcl-2 protein expressions in conjunction with cigarette smoking exposure and colorectal cancer risk in a hospital-based case-control study. A total of 163 colorectal cancer patients from Roswell Park Cancer Institute and Buffalo General Hospital and 326 healthy controls responded to a standardized questionnaire on colorectal cancer risk factors including detailed information on their history of cigarette smoking; 110 of the patients' tumours were available for immunohistochemical analysis of p27^Kip1 and bcl-2 protein overexpression. An avidin-biotin immunoperoxidase procedure was used to determine expression after incubation with mouse monoclonal p27^Kip1 and mouse monoclonal bcl-2 antibodies, respectively. A statistically significant trend for total pack-years of smoking was found when p27^Kip1 positive cases were compared with p27^Kip1 negative cases (trend test, p = 0.007). Although a weak inverse association was observed with smoking exposure among p27^Kip1 negative tumour cases in comparison to controls, a significant dose-response association was seen with p27^Kip1 positive tumours. The relative risk of developing a p27^Kip1 positive tumour was estimated to be 1.17 (95% CI 0.54-2.54) for those with less than 20 pack-years, 1.95 (95 % CI 0.95-3.97) for those with 20-39 pack-years, and 2.25 (95% CI 1.14-4.45) for those with greater than 39 pack-years of smoking exposure (trend test, p = 0.009) when compared with controls. When cases with bcl-2 expression were compared with cases without bcl-2 expression, suggestion of a trend was also observed with pack-years smoked (trend test, p = 0.09). In our study of 110 patients with sporadic colorectal cancer and 326 controls, we observed differences in associations between cigarette smoking and expressions in p27^Kip1 and bcl-2. Our data suggest that bcl-2 overexpression (or a bcl-2 dependent pathway) is associated with cigarette smoking in the development of colorectal cancer, whereas a loss of p27^Kip1 expression is not. These associations indicate that there is aetiological heterogeneity in colorectal cancer development, and that they can indirectly allude to where these changes in protein expression occur in the adenoma-carcinoma sequence (i.e. early versus late events).     

Patterns and associations of smoking and electronic cigarette use among survivors of tobacco related and non-tobacco related cancers: A nationally representative cross-sectional analysis

BackgroundTobacco-use among cancer survivors leads to preventable morbidity, mortality, and increased healthcare costs. We sought to explore the prevalence of smoking and e-cigarette use among survivors of tobacco and non-tobacco related cancers.MethodsA cross-sectional analysis was conducted using the 2015–2018 National Health Interview Survey. Our primary outcome was the prevalence of current cigarette smoking or e-cigarette use among adults with self-reported history of tobacco related or non-tobacco related cancer. Logistic regression analysis was to assess the association of reported cancer type with cigarette smoking or e-cigarette use. Secondary outcomes included yearly trends and dual use.ResultsA total of 12,984 respondents reported a history of cancer, representing a weighted estimate of 5,060,059 individuals with a history of tobacco-related malignancy and 17,583,788 with a history of a tobacco and non-tobacco related cancer, respectively. Survivors of tobacco-related cancers had a significantly higher prevalence of current cigarette use (18.2 % vs 9.7 %, P < 0.0001), e-cigarette use (2.7 % vs 1.6 %, P < 0.0001) and similar rates of dual use. The prevalence of cigarette smoking among all survivors increased as time increased from the year of diagnosis up to 2 years post-diagnosis (P = 0.047). Odds of reporting current cigarette smoking use was higher for survivors of tobacco-related cancers, adjusted for sociodemographic factors (OR1.69, 95 % CI 1.44−1.99).ConclusionsSurvivors of tobacco-related cancers have a higher prevalence of current cigarette smoking and e-cigarette use compared to survivors of non-tobacco related cancers. There was a sequential increase in the prevalence of cigarette use during each subsequent year from the time of a new cancer diagnosis, underscoring the need for long term tobacco cessation support among newly diagnosed adults with cancer.     

Risk of adult acute and chronic myeloid leukemia with cigarette smoking and cessation

BackgroundCigarette smoking is an established risk factor for adult myeloid leukemia, particularly acute myeloid leukemia (AML), but less is known about the nature of this association and effects of smoking cessation on risk.MethodsIn a large population-based case–control study of myeloid leukemia that included 414 AML and 185 chronic myeloid leukemia (CML) cases and 692 controls ages 20–79 years, we evaluated risk associated with cigarette smoking and smoking cessation using unconditional logistic regression methods and cubic spline modeling.ResultsAML and CML risk increased with increasing cigarette smoking intensity in men and women. A monotonic decrease in AML risk was observed with increasing time since quitting, whereas for CML, the risk reduction was more gradual. For both AML and CML, among long-term quitters (≥30 years), risk was comparable to non-smokers.ConclusionsOur study confirms the increased risk of myeloid leukemia with cigarette smoking and provides encouraging evidence of risk attenuation following cessation.     

Lung cancer risk in germline p53 mutation carriers: association between an inherited cancer predisposition,cigarette smoking,and cancer risk

We recently observed a significantly increased risk for lung cancer in carriers of p53 germline mutations. Because cigarette smoking is known to play an important role in increasing the risk for lung cancer in the general population, we wanted to determine the role of cigarette smoking in lung cancer risk in people with a genetic susceptibility based on a p53 germline mutation. We studied 1263 people from 97 families enrolled in a cohort study of families systematically ascertained through childhood soft-tissue sarcoma patients treated at the M.D. Anderson Cancer Center, University of Texas, between 1944 and 1975. We assessed the incidence of lung and smoking-related cancers in 33 carriers of germline p53 mutations and in 1,230 noncarriers to determine whether there was an association between an inherited cancer predisposition, cigarette smoking, and cancer risk. We analyzed the association between cigarette smoking, mutation status, and lung and other smoking-related cancers by the Kaplan-Meier method and the Cox proportional hazards model with adjustments for birth year, race, and sex. In the hazards model, we incorporated a robust variance estimation to adjust for familial correlation. We observed an increased risk of a variety of histological types of lung cancer in the carriers of the p53 germline mutation. Mutation carriers who smoked had a 3.16-fold (95% confidence interval =1.48–6.78) higher risk for lung cancer than the mutation carriers who did not smoke. Our results demonstrate that cigarette smoking significantly increases lung cancer risk in carriers of a germline p53 mutation. This finding could be useful in designing strategies for early detection and treatment of lung and smoking-related cancers in individuals with this inherited cancer predisposition.     

Nicotine increases cancer stem cell population in MCF-7 cells

Epidemiological studies have suggested that cigarette smoking is related to increased breast cancer risk. Nicotine is most likely related to the risk in cigarette smoking. However, the mechanisms by which nicotine promotes cancer development are not fully understood. It has recently been suggested that development of breast cancer are originated from cancer stem cells, which are a minor population of breast cancer. In the present study, we investigated the effects of nicotine on the population of cancer stem cells in MCF-7 human breast cancer cells, using flow cytometry with a cancer stem cell marker aldehyde dehydrogenase (ALDH). We found that nicotine increased ALDH-positive cell population in a dose-dependent manner. We further demonstrated that a PKC-Notch pathway is involved in the effect of nicotine. In addition, the effect of nicotine was blocked by treatment with the α7 subunit-selective antagonist of nicotinic acetylcholine receptors (nAChR) α-Bungarotoxin. These data suggest that nicotine increases the stem cell population via α7-nAChR and the PKC-Notch dependent pathway in MCF-7 cells. These findings reveal a relationship between nicotine and the cancer stem cells in human breast cancer.     

Expression of p27Kip1 and bcl-2, cigarette smoking, and colorectal cancer risk

Although a positive association between cigarette smoking and colorectal adenoma development is consistently found, the association with colorectal cancer remains controversial. We evaluated the potential roles of p27^Kip1 and bcl-2 protein expressions in conjunction with cigarette smoking exposure and colorectal cancer risk in a hospital-based case-control study. A total of 163 colorectal cancer patients from Roswell Park Cancer Institute and Buffalo General Hospital and 326 healthy controls responded to a standardized questionnaire on colorectal cancer risk factors including detailed information on their history of cigarette smoking; 110 of the patientsfitumours were available for immunohistochemical analysis of p27^Kip1 and bcl-2 protein overexpression. An avidin?biotin immunoperoxidase procedure was used to determine expression after incubation with mouse monoclonal p27^Kip1 and mouse monoclonal bcl-2 antibodies, respectively. A statistically significant trend for total pack-years of smoking was found when p27^Kip1 positive cases were compared with p27^Kip1 negative cases (trend test, p = 0.007). Although a weak inverse association was observed with smoking exposure among p27^Kip1 negative tumour cases in comparison to controls, a significant dose?response association was seen with p27^Kip1 positive tumours. The relative risk of developing a p27^Kip1 positive tumour was estimated to be 1.17 (95% CI 0.54?2.54) for those with less than 20 pack-years, 1.95 (95 % CI 0.95?3.97) for those with 20?39 pack-years, and 2.25 (95% CI 1.14?4.45) for those with greater than 39 pack-years of smoking exposure (trend test, p = 0.009) when compared with controls. When cases with bcl-2 expression were compared with cases without bcl-2 expression, suggestion of a trend was also observed with pack-years smoked (trend test, p = 0.09). In our study of 110 patients with sporadic colorectal cancer and 326 controls, we observed differences in associations between cigarette smoking and expressions in p27^Kip1 and bcl-2. Our data suggest that bcl-2 overexpression (or a bcl-2 dependent pathway) is associated with cigarette smoking in the development of colorectal cancer, whereas a loss of p27^Kip1 expression is not. These associations indicate that there is aetiological heterogeneity in colorectal cancer development, and that they can indirectly allude to where these changes in protein expression occur in the adenoma?carcinoma sequence (i.e. early versus late events).     

Acquired and genetic susceptibility to cervical cancer

Infection with high-risk human papilloma virus (HPV) is a necessary risk factor for the development of cervical cancer (CC). However, there are many factors that contribute to the development of CC. We have been investigating the role of polymorphisms in chemical metabolizing genes and life-style factors in the development of CC between two countries with significantly different prevalence of CC. Our data confirm that infection with high-risk HPV is the most significant risk factor for CC in both Venezuela and US. In Venezuela, having multiple sex partners and early sexual activities are significant risk factors (OR=4.7, 95% CI=1.7-13.1; OR=6.7, 95% CI=2.3-20.1, respectively). On the other hand, cigarette smoking is the significant risk factor for women in the US (OR=6.4, 95% CI=1.8-23.2). Genotype analyses were conducted using specimens from the US population only. The GSTM1 null genotype was associated with a significant 3.4 fold increase in risk (95% CI=1.0-11.8) compared with those who were GSTM1 positive, after adjustment for smoking and HPV infection. Polymorphosis in CYP2E1 and mEH are associated with a non-significant increase in risk. Our study indicates that different acquired and genetic susceptibility factors can make significant contributions to the development of environmental disease such as cervical cancer.     

Combined genetic polymorphism and risk for development of lung cancer

Susceptibility to lung cancer has been shown to be modulated by host specific factors. Inheritance of different polymorphic cytochrome P450s (CYPs) and the glutathione S-transferases (GSTs) which affect metabolism of environmental toxicants may play a key role in individual susceptibility. Although individual polymorphic genes have been reported to be associated with development of lung cancer, little is known about the combined effects of several genes in carcinogenesis. From our study of 54 lung cancer patients and 50 matched controls, we observed that a combination of several versions of ‘unfavorable' metabolizing genes (CYP2D6, CYP2E1, GSTM1 and GSTT1) is strongly associated with lung cancer. The relative risk for the different combinations of these genotypes ranged between 1.3 and 14, with higher risk involving the activating genes. The duration and intensity of heavy smoking (expressed in pack-years) are the most important determinant for the development of lung cancer. For example, the estimated risk for development of lung cancer associated with smoking >30 pack-years is represented by an odds ratio=6.65; 95% CL=2.3–19.9 irrespective of an individual's genotype, whereas for smoking between >30 and <50 pack-years, odds ratio=4.5; 95% CL=1.37–15; and for smoking >50 pack-years, odds ratio=30; 95% CL=5.7–114. On the other hand, smoking of less than 30 pack-years is associated with an increased risk in the presence of the polymorphic genes (odds ratio=2.5; 95% CL=0.32–54). The results of our study indicate that the inheritance of multiple ‘unfavorable' genotypes, especially activating genes, is a crucial predisposing factor for the development of lung cancer from cigarette smoking. In addition, the genes may cause moderate smokers who would normally outlive the deleterious effects of smoking to develop lung cancer. The information can therefore be used to target individuals for prevention of health problems.     

Five-Year Prognosis Model of Esophageal Cancer Based on Genetic Algorithm Improved Deep Neural Network

ObjectivesEsophageal cancer is a high occult malignant tumor. Even with good diagnosis and treatment, the 5-year survival rate of esophageal cancer patients is still less than 30%. Considering the influence of clinical characteristics on postoperative esophageal cancer patients, the construction of a neural network model will help improve the poor prognosis of patients in the five years.Material and methodsIn this study, genetic algorithm optimized deep neural network is exploited to the clinical dataset of esophageal cancer. The independent prognostic factors are screened by Relief algorithm and Cox proportional risk regression. FTD prognostic staging system is established to assess the risk level of esophageal cancer patients.ResultsFTD staging system and independent prognostic factors are integrated into the genetic algorithm optimized deep neural network. The Area Under Curve (AUC) of FTD staging system is 0.802. FTD staging system is verified by the Kaplan-Meier survival curve, and the median survival time is divided for different risk grades. The FTD staging system is superior to the TNM stages in the prognosis effect. The AUC of deep neural network optimized by genetic algorithm is 0.91.ConclusionThe deep neural network optimized by genetic algorithm has good performance in predicting the 5-year survival status of esophageal cancer patients. The FTD staging system has a significant prognostic effect. The FTD staging system and genetic algorithm optimized deep neural network can be successfully availed in clinical diagnosis and treatment.