口咽鳞癌组织中HPV16感染和p16蛋白表达的临床意义

目的:检测口咽鳞癌中HPV16感染及p16表达率,并分析临床意义。方法:采用原位杂交法检测60例口咽鳞癌组织中HPV16的表达,免疫组化法检测95例口咽鳞癌组织p16的表达情况,分析HPV16与p16的相关性,总结上述两种蛋白在口咽癌中的临床意义。结果:口咽鳞癌组织中HPV16感染率为48.3%（29/60）,p16阳性表达率为52.6%（50/95）,60例标本中HPV16感染与p16表达显著相关（P<0.001）,用p16表达预测HPV16感染的正确率可达90%（54/60）,跟国内外报道一致。p16阳性组相比p16阴性组,吸烟、饮酒、非嚼槟榔、T3+T4、有淋巴结转移、III-IV临床分期和高分化者所占比例更低,但不具有统计学差异(P>0.05)。平均随访时间38个月,随访率65.3%（62/95）,62例口咽鳞癌病人中p16阳性组和p16阴性组的3年总体生存率和无瘤生存率分别为70.4%对比40.0%（P=0.008）和63.0%对比25.7%（P=0.004）。总体生存率多因素分析提示,p16阴性病人死亡风险是p16阳性病人的2.12倍(HR 0.471,95%CI 0.201-1.103,P=0.083),无瘤生存率多因素分析提示,p16阴性病人死亡风险是p16阳性病人的2.36倍(HR 0.432,95%CI 0.201-0.891,P=0.024),p16与口咽癌的预后密切相关。结论:p16表达和HPV16表达存在紧密相关性,p16可以替代HPV16来预测预后,p16蛋白阳性口咽癌患者具有非吸烟、非饮酒、嚼槟榔和肿瘤分化程度低的趋势,检测p16表达对口咽癌病人预后判断有重要的提示意义。     

肺鳞癌中人乳头瘤病毒与p53和Rb积聚的关系

目的探讨肺鳞癌组织中人乳头瘤病毒(humanpapillomavirus,HPV)感染与p53蛋白和Rb蛋白表达的关系并分析作用机理。方法采用地高辛标记的HPV-DNA探针,用原位杂交法检测84例肺鳞癌49例支气管黏膜慢性炎标本,组织中的HPV-DNA存在情况,并用免疫组化SABC法检测肺鳞癌组织中p53及Rb蛋白。结果HPV原位杂交阳性信号位于细胞核内,肺鳞癌HPV检出率为48.81%(41/84)、对照组黏膜慢性炎HPV检出率为6.12%(3/49),两组比较差异有统计学意义(P=0)。84例肺鳞癌中31例检出Rb蛋白表达,其中18例HPV阳性,13例HPV阴性,HPV阳性组与阴性组差异无统计学意义(P=0.2588)。84例肺鳞癌中30例检出p53蛋白表达,其中17例HPV阳性,13例HPV阴性,HPV阳性组与阴性组差异无统计学意义(P=0.3634)。结论肺鳞癌与HPV感染关系密切,肺鳞癌组织中也存在p53蛋白积聚,p53蛋白积聚与HPV感染无明显相关性,Rb蛋白积聚与HPV感染无明显相关性。     

口咽鳞癌HPV感染与p16表达及放疗预后相关性研究

目的 探讨口咽鳞癌HPV感染与p16表达及放疗预后相关性,以及p16是否有预测放疗预后的价值。方法 对1999—2008年间本院42例初治口咽鳞癌组织标本采用PCR检测HPV-DNA,采用免疫组织化学法检测p16表达情况。对HPV、p16不同状态肿瘤根治性放疗后局部区域CR及HPV感染与p16表达相关性比较行χ²检验,Kaplan-Meier法计算OS并Logrank法检验。     

HSP70、p53和c—myc在宫颈鳞癌中的表达及与HPV16／18感染的关系

目的探讨热休克蛋白70(heat shock protein 70,HSP70)、抑癌基因p53、原癌基因c-myc在宫颈鳞癌中的表达及其与人乳头瘤病毒(HPV)感染的关系。方法采用免疫组化技术检测45例宫颈鳞癌、12例宫颈原位癌和20例正常宫颈组织中HSP70、p53、c-myc蛋白的表达,同时采用聚合酶链反应(PCR)技术检测HPV16/18的感染情况。结果①宫颈原位癌和宫颈癌中HSP70、p53、c-myc蛋白表达均显著高于正常宫颈组织。②HPV16/18阳性组HSP70表达明显高于HPV16/18阴性组,HPV16/18阴性组p53表达明显高于HPV16/18阳性组,但c-myc表达差异无显著性。结论在HPV感染的应激状态下,HSP70在宫颈鳞癌中过表达,p53则表达降低,c-myc蛋白的表达与HPV感染无相关性。     

口腔、口咽鳞状细胞癌中HPV感染与EGFR之间的相关性研究

目的：通过检测人乳头状病毒 (human papilloma virus, HPV)感染相关蛋白P16与表皮生长因子受体（epidermal growth factor receptor, EGFR）在口腔、口咽鳞癌中的表达，探索HPV感染与EGFR之间的关系，以及探讨P16、EGFR蛋白在口腔、口咽鳞癌中的表达差异及其临床病理意义。方法：收集53例口腔鳞癌和35例口咽鳞癌组织标本及其临床资料，采用免疫组化法检测P16、EGFR蛋白的表达情况，并结合临床资料分析临床意义。同时采用t检验、2检验和分类变量的关联性分析法分析数据。结果：本组88例患者中P16阳性率为40.9%，EGFR阳性率为69.3%，P16与EGFR在口腔、口咽鳞癌中具有相关性（P<0.05，2=14.77，r=0.379）。口腔鳞癌患者P16阳性率为22.6%(12/53)，口咽鳞癌患者阳性率为68.6%(24/35)，两者差异有统计学意义（P<0.000），口腔鳞癌患者EGFR阳性率为56.6 %(30/53)，口咽鳞癌患者阳性率为88.6%(31/35)，两者差异有统计学意义（P<0.001）。P16阳性组患者的吸烟情况、肿瘤分化程度、复发情况和患者性别与阴性组患者比较，差异均有统计学意义（均P<0.05）。EGFR阳性组和阴性组仅在患者性别情况比较上，有统计学差异（P<0.05）。结论：在口腔、口咽鳞癌中P16的表达与EGFR呈正相关，说明HPV感染状态可能影响EGFR的表达，P16、EGFR在口腔与口咽上的表达分布存在差异。P16表达与肿瘤复发、分化程度、患者性别及吸烟情况有关。     

广东省潮汕地区单中心头颈部鳞状细胞癌患者人乳头瘤病毒初步检测分析

目的探讨广东省潮汕地区单中心头颈部鳞状细胞癌(HNSCC)患者人乳头瘤病毒(HPV)感染及亚型状况。方法收集2014年12月至2016年12月汕头大学医学院附属肿瘤医院167例HNSCC患者的肿瘤原发灶标本。采用免疫组织化学(IHC)法检测肿瘤组织中p16蛋白的表达,以肿瘤细胞p16蛋白阳性率≥76%为判断HNSCC存在HPV的依据,分析p16蛋白与患者临床病理因素的关系。采用原位杂交法(ISH)检测肿瘤组织中是否存在HPV 16、18 DNA;应用RNAscope法检测肿瘤组织中18种常见的高危HPV亚型(HPV HR 18)RNA的表达情况,分析p16蛋白阳性细胞比例≥50%的肿瘤组织中HPV HR 18阳性情况。结果患者p16蛋白强表达率为7.2%(12/167);低龄组(<50岁)p16蛋白强表达率高于高龄组(≥50岁)[17.2%(5/29)比5.1%(7/138),χ^2=5.321,P=0.021];口咽癌组p16蛋白强表达率高于非口咽癌组[29.4%(5/17)比4.7%(7/150),χ^2=14.019,P<0.01];性别、烟酒嗜好及肿瘤分期分层患者间p16蛋白强表达率差异均无统计学意义(均P>0.05)。ISH检测示,全部HNSCC原发灶均未发现HPV 16、18 DNA,重复实验结果一致。RNAscope法检测示,肿瘤细胞p16蛋白阳性率≥50%的19例患者中,3例(15.8%)肿瘤组织HPV HR 18 RNA阳性。结论潮汕地区HNSCC患者的HPV阳性率较低,以口咽癌患者最高,且呈年轻化趋势。潮汕地区HNSCC主要致HPV亚型可能并非HPV 16、18,而可能是包括HPV HR 18中的其他致病亚型。     

外阴鳞癌组织中p14ARF表达与人乳头状瘤病毒感染状态关系的研究

目的:探讨p14ARF表达与不同HPV感染状态的外阴鳞癌发生和发展的关系.方法:采用RT-PCR和蛋白印迹技术检测42例外阴鳞癌组织、10例正常外阴组织中p14ARF基因mRNA及蛋白表达水平,PCR技术检测其HPV-DNA,分析HPV阳性组和阴性组外阴鳞癌组织中,p14ARF基因mRNA及蛋白表达与其临床病理特性的关系.结果:外阴鳞癌组p14ARF基因mRNA及蛋白表达强度为0.92±0.24和1.09±0.11;正常外阴组分别为0.93±0.06和1.02±0.38,两组比较差异无统计学意义,P>0.05;低、中和高分化鳞癌组p14ARF基因mRNA表达分别为0.98±0.11、0.94±0.15和0.91±0.07;p14ARF基因蛋白表达低、中和高分化分别为1.14±0.24、1.11±0.27和1.07±0.29,3组间比较差异均无统计学意义,P>0.05.p14ARF基因mRNA及蛋白在HPV阳性组表达强度分别为0.99±0.04和1.11±0.02,HPV阴性组表达强度分别为0.61±0.07和0.76±0.06, 两组比较差异有统计学意义,P<0.05.结论:p14ARF可能参与了外阴鳞癌的发生发展过程,并可能成为HPV感染的外阴鳞癌发生进展相关的基因.     

HPV检测原发灶不明颈淋巴结转移癌的诊断作用初探(附6例报告)

目的 初步探讨HPV检测在诊断原发灶不明的颈淋巴结转移性鳞癌中的价值。方法 收集复旦大学附属肿瘤医院6例首诊为原发灶不明的颈淋巴结转移性鳞癌,最终确诊为HPV相关口咽鳞癌,分析确诊过程。结果 首诊时6例患者均被确诊为颈淋巴结转移性鳞癌,且p16表达阳性和HPV-16亚型阳性,而EBER表达阴性。经全面检查均未发现明显的原发病灶。随后对其中4例予同侧扁桃体盲检(2例)和切除(2例),病理均证实为扁桃体鳞癌。另2例分别在随访第149天、545天MRI检查发现同侧口咽侧壁和舌根增厚伴强化,经活检分别证实为扁桃体鳞癌、舌根鳞癌。结论 对于原发灶不明的HPV阳性颈淋巴结转移性鳞癌,应高度怀疑原发病灶来源于口咽部位的可能性,特别是扁桃体和舌根部位。     

子宫肿瘤HPV16/18DNA感染与TNF表达的相关性研究

目的 :探讨子宫肿瘤人乳头瘤 (HPV) 16/ 18DNA病毒感染与TNF表达是否存在相关性。方法 :分别应用非同位素原位杂交技术及免疫组化方法选择性对 3个传代的细胞系及 96例宫颈标本和75例子宫内膜标本进行了HPV16/ 18DNA感染及TNF表达的研究。结果 :SiHa、W 12细胞系HPV16/18DNA感染为阳性 ,NCx细胞系为阴性 ;正常宫颈组织、CINⅠ、CINⅢ、宫颈鳞癌阳性表达分别为 2例、5例、9例、2 7例 ,四组差异有极显著性 (P <0 .0 1) ;正常子宫内膜组织均为阴性 ,子宫内膜癌阳性表达 10例。正常宫颈组织、正常内膜组织TNF蛋白、TNFmRNA均未有阳性表达。宫颈癌 2 5例 ,子宫内膜癌 13例TNF蛋白为阳性 ,宫颈癌 2 2例 ,子宫内膜癌 16例TNFmRNA为阳性。宫颈癌HPV16/ 18感染与TNF蛋白表达两者均为阳性的为 2 2例 ;HPV16/ 18阴性、TNF蛋白阳性的 3例 ;子宫内膜癌两者均阳性的为 8例 ;HPV16/ 18阴性、TNF蛋白阳性的 5例。结论 :HPV16/ 18阳性者TNF蛋白表达明显高于阴性者 ,以宫颈鳞癌最为显著 (P <0 .0 1)。     

bcl-2蛋白在原发性肺鳞癌中的表达及其意义

目的:探讨bcl-2蛋白在原发性肺鳞癌中的表达及其意义。方法:应用s—p免疫组化方法检测手术切除后随访5年以上的66例肺鳞癌标本中bcl—2蛋白的表达。结果:bcl—2蛋白在原发性肺鳞癌中表达阳性率为27.3％(18/66),其表达与分化程度密切相关(X~2=10.09,P<0.005;x~2=7.58,P<0.01)。淋巴结癌转移阳性组bcl—2蛋白阳性表达率(28.6％),淋巴结癌转移阴性组(26.6％)。bcl—2蛋白表达阳性组病人的预后显著差于bcl—2蛋白阴性表达组(X~2=9.37,P<0.005):结论:bcl—2蛋白表达的改变对肺鳞癌的生物学行为起一定作用,并可作为评估预后的指标。     

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.     

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.     

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.