恶性肿瘤患者血清骨钙素、甲状旁腺素含量与骨转移的相关性研究

目的：观察恶性肿瘤患者血清骨钙素（OC）、甲状旁腺素（PTH）的含量变化与骨转移发生、发展的关系。方法：放射免疫检测恶性肿瘤患者70例和正常健康人30例血清OC和PTH水平。结果：OC水平骨转移组高于正常对照组（P〈0．02），非骨转移组低于正常对照组（P〈0．01），骨转移组明显高于非骨转移组（P〈0．001），PTH水平骨转移组高于正常对照组（P〈0．01），非转移组与正常对照组比较无明显变化（P〉0．05），骨转移组明显高于非骨转移组（P〈0．01）。骨转移组转移病灶的数量与OC、PTH的含量成正相关。结论：血清OC、PTH对骨转移诊断具有一定临床价值。     

PTH治疗骨质疏松症的研究进展

甲状旁腺素(PTH)是由甲状旁腺分泌的含84个氨基酸的单链多肽蛋白质，它是调节钙、磷代谢及骨转换的最为重要的肽类激素之一。传统认为PTH是刺激骨分解的骨代谢调节激素。它直接作用于骨和肾，靶细胞为成骨细胞及肾小管细胞，促进骨钙动员和肾对钙的重吸收，通过促进1-α羟     

骨钙素甲状旁腺素和碱性磷酸酶联检对恶性肿瘤骨转移的临床意义

恶性肿瘤晚期常发生骨转移而引起骨生化和结构的改变.骨钙素(Osteocalein,OC)是由成骨细胞产生和分泌的一种非胶原蛋白,具有骨代谢调节激素的作用,因其血中成分最主要来源于骨,被认为是目前反映骨代谢比较敏感及特异性的指标.     

国产氯屈膦酸二钠（洛屈）

氯屈膦酸二钠(Clodronate disodium)是人工合成的焦磷酸类似物,属双膦酸盐类的骨代谢改善剂.对骨组织有特异性吸附作用,通过防止羟磷灰石结晶溶解、减少破骨细胞的数量和强力抑制破骨细胞的活性起到选择性抑制骨吸收作用.对各种骨吸收增加的骨代谢疾病(包括恶性肿瘤的溶骨性转移和高钙血症、骨质疏松症、佩吉特氏病)均有显著疗效,其作用强度是第一代双膦酸盐的十倍.氯屈膦酸二钠对磷酸钙有很强的亲和性,能改善骨的组织结构,在处理溶骨性骨转移的过程中,突破了传统的措施,开拓了新的治疗方法,能有效地防治或延迟由癌肿引致的溶骨性骨转移及继续恶化,并可减少病理性骨折,而不影响正常的骨矿化作用;对消除骨转移灶及高钙血症引起的剧痛十分有效;并能防治高钙血症及保持血清钙浓度正常.最新研究表明,氯屈膦酸二钠还可以通过与细胞杀伤因子协同,以及影响恶性肿瘤骨转移所涉及到的过程(凋亡、粘附分子和蛋白酶)来减少肿瘤的骨转移及内脏转移.     

骨代谢标志物ICTP、BAP对肺癌骨转移的诊断意义

背景与目的骨代谢标志物是一类源于骨基质或骨细胞的代谢指标,可反映骨代谢情况。本研究旨在探讨血清骨代谢生化指标I型胶原交联羧基端肽(cross-linked telopeptide of type I collage,ICTP)和骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,BAP)在肺癌骨转移诊断中的意义及其临床应用价值。方法采用前瞻性对照方法,共入组110例,分为3组。初治肺癌患者共90例,临床分期为IV期,分为骨转移组50例和非骨转移组40例,健康对照组20例,采用酶联免疫法和电化学发光免疫测定法检测所有入组者治疗前的血清骨代谢生化指标ICTP和BAP水平,对骨转移的各因素与血清ICTP和BAP的相关性进行统计学分析。结果骨转移组的血清ICTP和BAP水平显著高于非骨转移组和健康对照组(P<0.05)。多发性骨转移组(骨转移数≥3)的血清BAP水平显著高于少发性骨转移组(骨转移数<3)(P<0.05)。混合性骨转移组的血清BAP水平显著高于溶骨性骨转移组(P<0.05)。ICTP和BAP在肺癌骨转移诊断中的敏感性分别为18%和40%,特异性分别为98.3%和95...     

唑来膦酸治疗恶性肿瘤骨转移临床应用新进展

唑来膦酸属于第三代双膦酸盐.治疗恶性肿瘤骨转移临床疗效确切,应用前景广泛.唑来膦酸在体外可抑制破骨细胞活动,诱导破骨细胞调亡;还可以抑制由肿瘤释放的多种刺激因子引起的破骨细胞活动增强和骨钙释放;缓解实体瘤患者骨转移引起骨痛,起效迅速,效果明显.     

OPG RANKL和RANK在肿瘤骨转移中的作用

健康的骨骼依靠骨形成和骨吸收的动态平衡来维持完整性.其发生和重建过程分别由破骨细胞(osteoclast OC)介导的骨吸收和成骨细胞(osteoblast OB)介导的骨形成来完成.在疾病过程中,吸收与形成的平衡被打破,导致骨骼形态结构的异常,出现成骨性损伤、溶骨性损伤或混合损伤.肿瘤骨转移后可出现压迫、疼痛、骨折等症状,严重影响患者的生活质量,是死亡的重要原因.目前认为,肿瘤骨转移发生的前提条件之一是在转移部位的骨溶解过度.OPG RANKL和RANK作为骨吸收的重要调节因子,在肿瘤骨转移过程中的作用日益受到人们的重视,以下就其研究进展综述如下.     

国产氯屈膦酸二钠(洛屈)

 氯屈膦酸二钠(Clodronate disodium)是人工合成的焦磷酸类似物, 属双膦酸盐类的骨代谢改善剂。对骨组织有选择性吸附作用, 通过防止羟磷灰石结晶溶解、减少破骨细胞的数量和直接强力抑制破骨细胞的活性起到抑制骨吸收作用, 对各种骨吸收增加的骨代谢疾病(包括恶性肿瘤的溶骨性转移和高钙血症、骨质疏松症、佩吉特氏病)均有显著疗效, 其作用强度是第一代双膦酸盐的十倍。氯屈膦酸二钠对磷酸钙有很强的亲和性, 能改善骨的组织结构, 在处理溶骨性骨转移的过程中, 突破了传统的措施, 开拓了新的治疗方法, 能有效地防治或延迟由癌症引致的溶骨性骨转移及继续恶化, 并可减少病理性骨折, 而不影响正常的骨矿化作用; 对消除骨转移灶及高钙血症引起的剧痛十分有效; 可防治高钙血症及保持血清钙浓度的正常水平。最新研究表明, 氯屈膦酸二钠还可以通过与细胞杀伤因子协同, 以及影响恶性肿瘤骨转移涉及到的过程(凋亡、粘附分子和蛋白酶) 来减少肿瘤的骨转移和内脏转移。     

人重组甲状旁腺素治疗骨质疏松及其骨折的研究进展

人体天然甲状旁腺素（hPTH）含有84个氨基酸。人重组甲状旁腺素1—34具有与人体天然甲状旁腺素N端34个氨基酸序列完全相同的结构，其生物学作用亦是通过与特异性高亲和性人体天然甲状旁腺素-Ⅰ受体结合介导的。PTH的N端与C端在骨代谢中发挥作用不尽相同，N端主要与经典PTHⅠ型受体结合，影响成骨作用；[第一段]     

甲状旁腺素相关肽与肿瘤

甲状旁腺素相关肽(PTHrP)参与调节钙磷代谢和多器官的生长发育,在恶性肿瘤发生骨转移和高钙血症过程中发挥重要作用.越来越多的研究证实PTHrP可以由多种类型的肿瘤细胞分泌,参与调节肿瘤细胞的增殖、侵袭,并与患者预后密切相关,为肿瘤治疗提供了新的靶点.     

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.     

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.     

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.     

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.     

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.     

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。     

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。     

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.