原癌基因Bmi-1与头颈部恶性肿瘤

Bmi-1基因是多梳基因家族的核心成员之一.作为一种原癌基因,Bmi-1基因在细胞的自我更新、增殖及凋亡方面发挥重要作用.多项研究已证实,Bmi-1基因在鼻咽癌、喉癌等多种头颈部恶性肿瘤中均有异常表达,并与肿瘤的发生、发展、侵袭、预后密切相关.Bmi-1基因有望成为一种新的肿瘤分子标志物,为头颈部恶性肿瘤的诊断、治疗提供新的方向和手段.     

头颈部肿瘤组织中PD-L1的表达及临床意义分析

目的 探讨头颈部肿瘤组织中细胞程序性死亡配体-1（PD-L1）的表达情况及临床意义。方法 将2015 年1 月至2016年6月收治的40例头颈部恶性肿瘤组织及20例头颈部囊肿组织的手术标本经包埋制作成蜡块,采用免疫组织化学SP二步法检测以上组织中的PD-L1蛋白表达情况,分析PD-L1表达水平与临床病理参数（年龄、性别、病理分化程度和临床分期）的关系。结果PD-L1在头颈部囊肿组织中不表达,头颈部肿瘤组织中的阳性表达率为65.0%（26/40）,高于头颈部囊肿组织,差异有统计学意义（P<0.05）。PD-L1表达与年龄、性别及病理分化程度无关（P>0.05）,而与患者的临床分期有关（P<0.05）。结论 PD-L1在头颈部恶性肿瘤组织中表达升高,可为头颈部恶性肿瘤的免疫靶向治疗提供参考。     

miRNA-16在常见头颈部恶性肿瘤中的研究进展

miRNAs是高度保守的内源性非编码小RNA分子,通过与特定mRNA 3’非翻译区(3’UTR)互补序列结合,降低靶基因的转录和/或蛋白水平。miRNAs在许多生理过程中发挥着重要作用,如代谢、分化等。然而,miRNAs异常表达也与肿瘤的发生发展相关。miRNA-16被证实在多种肿瘤中存在异常表达,故本文就miRNA-16在常见头颈部恶性肿瘤中的研究做一综述。     

hMLH1基因在头颈部恶性肿瘤中的研究进展

作为人类DNA错配修复系统的重要组成部分,hMLH1基因与很多恶性肿瘤的发生、发展密切相关.研究发现,hMLH1基因的失活可能参与了头颈部鳞癌的早期癌变过程,并且和癌组织分化程度、病灶数量、淋巴侵犯有关.此外,最新的研究结果表明甲状腺恶性肿瘤中,hMLH1高表达、异位表达与乳头状癌淋巴、血管侵犯以及恶性程度更高的甲状腺癌类型有关,这与传统上认为hMLH1失活与甲状腺癌发生、淋巴转移、BRAF突变高度相关的观点相悖,提示了hMLH1基因在甲状腺恶性肿瘤中可能存在两面性.全文就近年来hMLH1基因在头颈部鳞癌和甲状腺恶性肿瘤中的研究进展进行综述.     

HPV感染与口咽癌的关系

头颈部恶性肿瘤发病率在恶性肿瘤中排第六位,其中最常见的是头颈部鳞状细胞癌.主要起源于上呼吸道、上消化道黏膜,全球每年新发病例约645,000例.近年来我国头颈部肿瘤的发病率为15.22/10万.占全身恶性肿瘤的4.45％.因种族、文化和社会经济的地域差异,头颈部肿瘤的发病率存在很大差异.吸烟和饮酒是头颈部鳞状细胞癌的主要危险因素,但20％-25％的头颈部鳞癌患者不存在吸烟和饮酒的危险因素,越来越多的证据表明,高危型（16/18亚型）人乳头瘤病毒（Human Papillomavirus,HPV）感染与头颈部鳞状细胞癌密切相关.     

瞬时受体电位通道在头颈部恶性肿瘤中的研究进展

随着社会经济的不断发展,头颈部恶性肿瘤的发生率和病死率也不断上升,研究人员一直致力于寻求各种新的、有效的诊断和治疗癌症的方法。近年来研究发现瞬时受体电位（transient receptor potential,TRP）通道与头颈部恶性肿瘤关系密切。TRP通道主要非选择性渗透一价和二价阳离子。在头颈部恶性肿瘤中,TRP通道常处于表达失调状态,这可能导致肿瘤标志性功能的改变,如增殖、迁移、侵袭增强以及无法诱导细胞凋亡等。因此,TRP通道可以作为潜在的诊断生物标志物。TRP通道主要表达于细胞表面,离子通道类靶向药物不需要进入细胞,使TRP通道成为最佳的药物候选靶点。本文综述了TRP通道在头颈部恶性肿瘤中的研究进展,并对TRP通道作为肿瘤生物标志物或治疗靶点的潜力进行了展望。     

恶性肿瘤p53基因异常,nm23表达与化疗敏感性关系

目的探讨恶性肿瘤ｐ５３基因异常、ｎｍ２３表达与抗癌药耐药性关系。方法用ＭＴＴ法测定１７种常用抗癌药对７４例恶性肿瘤的体外敏感性，并用聚合酶反应———单链构象多态分析技术和免疫组织化学染色法检测其ｐ５３基因异常、ｎｍ２３表达情况。结果与ｐ５３基因正常、ｎｍ２３（＋）组比较，其余三组抗癌药抑制率较小，其中ｐ５３基因正常、ｎｍ２３（－）组抗癌药抑制率不存在显著差异；ｐ５３基因异常、ｎｍ２３（＋）组对两种抗癌药抑制率存在显著差异；ｐ５３基因异常、ｎｍ２３（－）组对７种抗癌药抑制率存在显著差异。结论当恶性肿瘤中存在ｐ５３基因异常或ｎｍ２３表达（－）时，抗癌药耐药性增加。     

转化生长因子β受体与肿瘤

许多恶性肿瘤细胞均有转化生长因子受体Ⅱ(transforming growth factor-β receptor typeⅡ,TGF-βⅡ)表达缺失或降低,从而使其逃脱TGFβ的生长控制而获得恶性增殖能力.在胃肠癌中,TGF-βRⅡ polyA序列的移码突变是造成受体表达异常的主要原因;头颈部癌中,TGF-βRⅡ点突变引起其蛋白产物磷酸化功能障碍;乳腺癌细胞TGF-βRⅡ表达缺失可能与其蛋白运输异常有关,基因及药物治疗可恢复TGF-βRⅡ表达,逆转肿瘤细胞恶性表型,为肿瘤治疗提供了新的发展方向.     

长链非编码RNA DANCR在甲状腺癌中的研究进展

甲状腺癌是最常见的头颈部恶性肿瘤,发病率呈逐年上升趋势。因此探究甲状腺癌的发生、发展机制,开发甲状腺癌诊断标志物和治疗靶点,对提高甲状腺癌的疗效、延长患者生存时间具有重要意义。前期研究中发现长链非编码RNA（lncRNA）DANCR在甲状腺癌中异常高表达,可通过影响miRNA-185-5p及转录因子SMARCB1来促进...     

单细胞测序技术在头颈部恶性肿瘤中的研究与发展

单细胞测序是针对单个细胞的遗传信息进行测序,能更好地认识细胞之间的差异,解决了普通测序带来的异质性问题。头颈部恶性肿瘤已经成为癌症相关疾病死亡的第六大病因,单细胞测序技术应用于揭示头颈部恶性肿瘤的异质性、描述头颈部恶性肿瘤的微环境、评估头颈部恶性肿瘤的侵袭、转移和评价治疗效果、评估治疗抵抗、探究循环肿瘤细胞的作用等方面,对头颈部恶性肿瘤发生发展的研究和个体化治疗方案的探索有着巨大的推动作用。本综述旨在概述单细胞测序的机理和意义,总结其在头颈部恶性肿瘤中的研究进展。     

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.     

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.     

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.     

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.