MMP-2和p53表达在结直肠癌组织中的表达及其临床意义

目的探讨人结直肠癌组织中基质金属蛋白酶-2（MMP-2）和p53表达与其临床病理特征的关系。方法采用免疫组化EliVisionTM plus法,检测40例结直肠癌、20例结直肠腺瘤和20例正常结直肠组织中MMP-2和p53蛋白表达水平。结果40例结直肠癌组织中MMP-2和p53阳性表达率分别为80．0％（32／40）和82．5％（33／40）,明显高于正常结直肠组织、结直肠腺瘤组织中的阳性率（均为0、30．0％）。MMP-2和p53在结直肠癌中的表达与患者年龄、性别、肿瘤大小、肿瘤发生部位均无相关性（P〉0．05）,与组织学分化程度呈负相关,分化程度越差,蛋白阳性表达率越高,有淋巴结转移组蛋白阳性表达率明显高于无淋巴结转移组（P〈0．05）,与TNM分期呈正相关（P〈0．05）。MMP-2表达与肿瘤浸润深度有关（P〈0．05）,有远处转移组MMP-2蛋白阳性表达率明显高于无远处转移组（P〈0．05）,p53表达与肿瘤浸润深度以及远处转移均无相关性（P〉0．05）。结直肠癌组织中MMP-2表达与p53蛋白表达呈正相关（γs’=0．3742,P=0．0069）。结论MMP-2表达与结直肠癌淋巴结侵袭转移有关,p53基因突变后MMP-2表达增强。联合检测MMP-2和p53在结直肠癌中的表达对评估结直肠癌病情有一定意义。     

肌动蛋白凝胶蛋白和肌动蛋白凝胶蛋白2在结直肠癌组织中的表达及 其临床意义

目的:探讨结直肠癌组织中肌动蛋白凝胶蛋白（transgelin,TAGLN）及肌动蛋白凝胶蛋白2（transgelin2,TAGLN2）的表达及其临床意义。方法:选取2012年至2013年在郑州大学附属肿瘤医院接受结直肠癌根治术治疗的89例结直肠癌患者病理组织标本及配对癌旁组织,采用免疫组织化学检测TAGLN和TAGLN2在结直肠癌组织中的表达情况,结合临床资料分析TAGLN、TAGLN2与结直肠癌患者临床病理特征及预后的关系。结果:TAGLN在结直肠癌组织中的阳性表达率为60.7%（54/89）,明显高于癌旁组织38.2%（34/89）,差异有统计学意义（P＜0.05）,TAGLN表达与结直肠癌患者的TNM分期、肿瘤分化程度、Ki67表达、淋巴结转移及远处转移明显相关（P均＜0.05）;TAGLN2在结直肠癌组织中的阳性表达率为69.7%（62/89）,明显高于癌旁组织31.5%（28/89）,差异有统计学意义（P＜0.01）,TAGLN2表达与结直肠癌患者的肿瘤分化程度、Ki67表达及远处转移显著相关（P均＜0.05）。相关分析显示, TAGLN蛋白表达与TAGLN2蛋白表达呈正相关（r=0.219,P=0.039）。Kaplan-Meier生存分析显示,患者生存时间与肿瘤分化程度、TNM分期、Ki67表达、远处转移、TAGLN和TAGLN2有关,差异有统计学意义（P均＜0.05）;多因素Cox回归结果显示,远处转移、TNM分期和TAGLN是影响结直肠癌患者预后的独立危险因素（P均＜0.05）。结论:对于结直肠癌患者,TAGLN的表达与TNM分期、肿瘤分化程度、Ki67表达、淋巴结转移和远处转移有关,TAGLN2的表达与肿瘤分化程度、Ki67表达和远处转移有关。TAGLN表达、TNM分期和远处转移为结直肠癌患者预后的独立影响因素。     

DAB2IP基因及蛋白在结直肠癌组织中的表达研究

目的 从mRNA和蛋白两个水平上探讨DAB2IP 在结直肠癌组织中的表达及意义。方法 应用核酸原位杂交和免疫组织化学两种方法分别检测127例结直肠癌组织和36例癌旁正常黏膜组织中DAB2IP的表达情况,分析DAB2IP基因及其蛋白表达与结直肠癌淋巴结转移、分化程度及Dukes分期等临床病理特征的关系。结果 结直肠癌组织中DAB2IP mRNA与蛋白的阳性表达率分别为85.04％、79.53％,低于癌旁正常组织的100.00％、94.45％,差异有统计学意义（P均＜0.001）。高、中分化到低分化结直肠癌组织中,DAB2IP的阳性表达率均逐渐下调,3组间差异有统计学意义 （P＜0.01）。结直肠癌无淋巴结转移组中的DAB2IP阳性表达率高于淋巴结转移组,且其mRNA与蛋白表达水平与淋巴结转移呈负相关（r=-0.2361,r=-0.3060;P均＜0.01）。DAB2IP的表达水平与Dukes分期有关,从A期到D期DAB2IP表达逐渐下调,差异有统计学意义（P＜0.01）; 但DAB2IP表达与结直肠癌患者的年龄、性别、发生部位及肿瘤大小均无关（P＞0.05）。结论 DAB2IP在结直肠癌的发生、发展中具有重要作用,且其表达水平与淋巴结转移呈负相关,可作为预测结直肠癌转移潜能及判断预后的一个重要指标。     

S100A4和E-Cad在大肠癌中的表达与侵袭转移的关系

目的:探讨S100A4和E-Cad蛋白表达与大肠癌侵袭转移及预后的关系.方法:应用免疫组织化学方法检测101例大肠癌组织和20例癌旁正常粘膜、34例淋巴结转移癌、17例肝转移癌及10例大肠腺瘤中S100A4和E-Cad的表达情况.结果:S100A4蛋白在大肠癌组织中表达明显高于正常组织和腺瘤(P＜0.05),S100A4蛋白的袁达与有无淋巴结转移、肝转移及Dukes分期有关(P＜0.05);E-Cad蛋白在大肠癌组织中表达明显低于正常组织和腺瘤(P＜0.05),E-Cad蛋白的表达与有无淋巴结转移、肝转移及大肠癌分化、分期有关(P＜0.05),生存分析采用Log-rank检验:生存期均无统计学意义(P＞0.05),两种蛋白在大肠癌组织中的表达呈负相关(P＜0.05).结论:S100A4蛋白在大肠癌组织中表达增强和E-Cad表达减弱与大肠癌侵袭转移有关.     

S100A4基因差异表达与结直肠癌分化、转移及预后的关系

目的：研究S100A4基因差异表达与结直肠癌分化、转移及预后的关系。方法：应用免疫组织化学sP法检测87例结直肠癌组织及癌旁结直肠组织中S100A4蛋白，并分析S100A4蛋白表达与结直肠癌临床病理因素及术后5年生存率的关系；免疫细胞化学SP法检测3种不同分化程度的结直肠癌细胞Caco-2、HT29、HCT116的S100A4蛋白表达，RT-PCR检测该3种细胞的S100A4 mRNA表达水平。结果：在癌旁结直肠组织腺上皮中S100A4蛋白不表达；在结直肠癌组织中S100A4蛋白的表达率为64．4％（56／87）；与癌旁结直肠组织比较。差异有统计学意义（P〈0．01）。S100A4蛋白在结直肠癌中的表达与临床分期、淋巴结转移和5年生存率有关（P〈0．05），与其他临床病理因素无关（P〉0．05）；3种结直肠癌细胞均表达S100A4蛋白;S100A4 mRNA表达水平的顺序依次为：HCT116最高，HT29次之，Caco-2最低；三者S100A4 mRNA表达水平差异有统计学意义（P〈0．01）。结论：S100A4基因表达和结直肠癌的发生发展、分化、侵袭转移及预后密切相关；S100A4蛋白可作为判定结直肠癌临床病理特征及判断预后的重要指标之一，也可能作为新的生物标志物及治疗结直肠癌浸润转移的潜在靶目标。     

Testin基因在结直肠癌组织中的表达及临床意义

背景与目的:人类Testin基因是一个定位于染色体7q31.2的候选抑癌基因.本实验研究人结直肠癌中候选抑癌基因Testin的表达,并分析其与结直肠癌临床病理特征的关系.方法:应用RT-PCR和免疫组化SP法检测60例患者结直肠癌组织及对应正常组织(距肿瘤15 cm以上)中Testin的表达.同时分析Testin的表达与患者临床病理特征的关系.结果:结直肠癌组织中Testin mRNA的表达水平显著低于正常组织(P<0.01);免疫组化结果显示Testin在31.7%(19/60)的结直肠癌组织中呈阳性,而在正常组织中有86.7%(52/60)阳性(P<0.01).统计分析结果发现,Testin蛋白与mRNA的表达与结直肠癌患者的性别、年龄、肿瘤部位无关(P>0.05),而与肿瘤浸润深度、分化程度、Dukes分期、T分期、有无淋巴结转移和远处转移有关(P<0.05).浸润越深、分化程度越低、Dukes分期越晚、T分期越晚、有淋巴结转移和有远处转移的癌组织的Testin表达明显降低;Testin蛋白与mRNA的表达呈显著正相关(r=0.75,P<0.05).结论:Testin在结直肠癌中的表达量显著下降,可能与结直肠癌的浸润、分化和转移相关,提示Testin基因表达下调可能对结直肠癌的发生、发展具有重要作用.可能成为判断结肠癌预后和浸润转移的生物学指标.     

HER-2基因和MMP-2基因在结直肠癌中的表达和临床意义

目的:探讨人表皮生长因子受体-2(HER-2) 和基质金属蛋白酶-2(MMP-2) 在结直肠癌中的表达及其临床意义.方法:采用抗生蛋白链霉素-生物素标记法(SP) 免疫组化检测法 ,用HER-2 抗体、MMP-2抗体标记 64 例结直肠腺癌组织标本,并以大肠腺瘤15例及远癌正常大肠组织12例作对照,检测HER-2和MMP-2.结果: HER-2 及MMP-2在远癌组织中阳性率低于腺瘤性息肉组及腺癌组的表达,有统计学意义(P<0.05),腺瘤样息肉组与腺癌组表达率无统计学意义(P＞0.05).在结直肠癌病例中MMP-2 、HER-2 表达与结直肠癌患者性别、年龄、肿瘤分化程度、肿瘤浸润层次无关 (P>0.05) ,而与Ducks分期、有无转移淋巴结相关,C和D期结直肠癌患者切片中MMP-2 、HER-2表达率明显高于A和B期的患者 (P<0.05),有淋巴结转移的患者表达率明显高于无淋巴转移患者(P<0.05).HER-2 与MMP-2 表达存在显著正相关(r=0.303).结论: MMP-2 、HER-2 在正常组织、腺瘤性息肉及腺癌中的表达逐步上调,MMP-2 和HER-2在结直肠癌组织中表达明显升高,可能促进了大肠癌的转移、进展.MMP-2 、HER-2基因可能在结直肠癌的演进中起协同作用.     

结直肠癌中FHIT蛋白的异常表达及其临床意义

目的探讨结直肠癌中脆性组氨酸三联体(FH IT)基因蛋白表达状况与临床病理指标的关系。方法采用半定量免疫印迹(W estern b lot)检测30例结直肠癌及其癌旁正常组织(≥5 cm)FH IT蛋白表达状况。结果30例癌组织有56.7%的FH IT蛋白表达异常,FH IT蛋白表达量与患者的年龄、性别、肿瘤部位、肿瘤大小及组织学类型无关(P>0.05)而与肿瘤的组织分化程度、浸润深度、Dukes分期和淋巴结转移有关(P<0.05)。在浸润深度越深、分化程度越低、Dukes分期越晚和有淋巴结转移的癌组织中,FH IT蛋白低表达越明显。结论FH IT蛋白表达状况可能与结直肠癌组织学分级、浸润程度、Dukes分期及淋巴结转移相关,提示FH IT蛋白表达降低可能对结直肠癌发生、发展具有重要作用。     

E-钙黏素和环氧化酶-2与结直肠癌的关系

目的：探讨E－钙黏素及环氧化酶－2在结直肠癌发生、发展中的意义。方法：应用免疫组化技术（S－P法）检测34例结直肠癌组织中E－钙黏素及环氧化酶－2的表达。结果：E－钙黏素在结直肠癌中的表达强弱与 癌组织的细胞分化程度、淋巴结转移和Dukes分期相关（P＜0．05）；而与发病年龄、性别及肿块部位无明显相关。31例癌组织和19例转移淋巴结环氧化酶－2表达明显升高，但与肿瘤的分化、分期、部位和患者的性别及年龄无明显关系。此外，E－钙黏素和环氧化酶－2在癌组织中的表达与在正常肠黏膜中的表达要比较均有非常显著性差异（P＜0．01）。结论：E－钙黏素和环氧化酶－2的异常表达可能是结直肠癌发生、发展过程中的1个重要环节，并起着重要的作用。     

癌胚抗原和环氧化酶2的表达与结直肠癌的关系

背景与目的：已有研究表明,癌胚抗原参与了细胞间的粘附;环氧化酶2可能参与了结直肠癌的发生过程。本研究拟探讨癌胚抗原及环氧化酶2在结直肠癌发生、发展中的意义。方法：应用免疫组化技术（SP法）检测34例结直肠癌组织、癌旁组织、正常粘膜及其中19例转移淋巴结标本中癌胚抗原及环氧化酶2的表达。结果：癌胚抗原在结直肠癌中的表达水平与癌组织细胞分化程度的相关性有统计学意义（P＜0．05）;而与淋巴结转移、Dukes‘分期、发病年龄、性别及肿块部位的相关性无统计学意义（P＞0．05）。环氧化酶2在大部分癌组织（31／34）和全部转移淋巴结中表达明显升高,但与肿瘤细胞的分化、分期、部位和患者的性别及年龄的相关性无统计学意义（P＞0．05）。此外,癌胚抗原和环氧化酶2在癌组织中的表达和在正常肠粘膜中的表达差异均有统计学意义（P＜0．01）。结论：癌胚抗原和环氧化酶2的异常表达可能是结直肠癌发生、发展过程中的一个重要环节。     

New and emerging radiosensitizers and radioprotectors

The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.     

Religiosity and Physical and Emotional Functioning Among African American and White Colorectal and Lung Cancer Patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

Fruit and vegetables and cancer risk

The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

肾上腺素能β受体与肿瘤生长及转移

大量研究表明肿瘤细胞可表达β受体，而一些神经递质、药物和社会心理因素可能通过β受体影响肿瘤的生长和转移，β受体激动剂、β受体阻滞剂以及抑郁等社会心理因素可加强或削弱这种作用。这为表达β受体肿瘤的治疗开辟了新的道路，提供了新的治疗靶点。     

Occupational and environmental radiation and cancer

Epidemiologic evidence on the relation between occupational and environmental radiation and cancer is reviewed. Studies of pioneering radiation workers, underground miners, and radium dial painters revealed excess cancer deaths and contributed to the setting of radiation protection standards and to theories of carcinogenesis. Occupational exposures today are generally much lower than in the past, thus any associated increases in cancer will be difficult to detect. Pooling investigations of these more recently exposed workers, however, has the potential to validate current estimates of risk used in radiation protection. New information on the effects of chronic radiation exposure also may come from studies in the former Soviet Union of Chernobyl clean-up workers and of workers at the Mayak nuclear facilities. Studies of environmental radiation exposures, other than radon, are largely inconclusive, due mainly to the difficulties in detecting the low risks associated with low dose exposures. Thyroid cancer, however, has been linked to environmental radiation from the Chernobyl accident and from nuclear weapons tests. Low-level radiation released during normal operations at nuclear plants has not been found to increase cancer rates in surrounding populations. Radon, a human carcinogen, is the most ubiquitous exposure to human populations; remediating high residential-radon levels is recommended, recognizing that the exposure can never be removed completely because it occurs naturally.     

Cell and tissue interactions in carcinogenesis and metastasis and their clinical significance

This review describes a new vision for future directions in the study of metastatic cancer biology and pathology. It is based upon clinical and experimental observations on the constituent cell lineages within a neoplasm and on tumour-host interactions. The vision incorporates information from studies in population biology, developmental biology and experimental pathology as well as investigations upon human malignant disease. The assembled information reveals that invasion and metastasis are supra-cellular manifestations of "emergent behavior" among combinations of normal and malignant cell lineages in vivo. Emergent behavior is a combinatorial interactive process in which a population displays new traits which cannot be achieved by individuals acting separately and which subside when the specific population mix disaggregates. Disruption of such pathological interactions in the field of a developing primary or secondary tumour is, therefore, required to disable the malignant population and arrest progression without tissue destruction. These conclusions originate, in part, from principles which govern the sociobiology and group behavior of bees, ants, fish, birds and human societies. In all these social organisms, external factors can disrupt signaling mechanisms and induce expanding self-perpetuating rogue behavior, leading to social disintegration. These principles also apply to cellular societies composing higher animals, which likewise need intrinsic rules to maintain social order and avoid anarchy, and recognition of this is essential for advancing future research on the mechanisms involved in carcinogenesis and metastasis. Summarised evidence is presented here to support the conclusion that miscommunications between cells and tissues in the region of the developing tumour and its metastases are the main direct perpetrators of malignant disease. Genetic lesions (mutations, deletions, translocations, reduplications, etc.), commonly seen in cancers, can significantly disrupt important molecular pathways in the networks of communications needed to sustain orderly tissue/organ structure and function. However, genetic lesions can also, themselves, be induced by abnormal cell interactions initiated by extrinsic carcinogenic agents such as chemicals, viruses, hormones and radiation. The evidence shows that, irrespective of the initiating cause, it is this miscommunication in the region of a developing tumour and its metastases that is ultimately responsible for the emergence and progression of the disease. The article describes how this information collectively, provides a framework for designing specific novel therapeutic approaches targeting the cell and tissue interactions driving tumour metastasis and its manifold effects on the whole body.     

Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: A comprehensive review and meta-analysis

Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60–3.53) and 1.64 (95% CI 1.02–2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63–1.13) for CM and 1.03 (95% CI 0.95–1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.