亚砷酸联合沙利度胺治疗难治性复发性多发性骨髓瘤的疗效

 【摘要】　目的　观察亚砷酸（ATO）联合沙利度胺治疗难治性复发性多发性骨髓瘤（MM）的疗效和安全性。方法　35例难治性复发性MM患者,给予ATO（10 mg／d）及维生素C（2 g／d）静脉滴注,连续应用14 d,每28 d为1个疗程;同时给予沙利度胺口服,起始剂量为50 mg／d,1周后逐步加量并调整至100～150 mg／d,长期维持。连续应用3个疗程后评估疗效和患者不良反应,有效患者继续沙利度胺维持治疗,并随访观察无进展生存（PFS）。采用参照欧洲血液和骨髓移植小组骨髓瘤疗效判定标准判定疗效,并按世界卫生组织（WHO）标准判定不良反应。结果　ATO联合沙利度胺治疗难治性复发性MM总有效率71.43 %（25／35）,完全缓解2例（5.71 %）,部分缓解12例（34.29 %）,微小反应 11例（31.43 %）,无效10例（28.57 %）。25例患者进入维持治疗后,中位随访期为11个月（2～31个月）,中位PFS 9个月。主要不良反应有消化道反应、白细胞减少、肝功能损害、手足麻木等,不良反应轻微,均可耐受。结论　ATO联合沙利度胺治疗难治性复发性MM有效、可行,并有较好的治疗顺从性。     

沙利度胺联合地塞米松治疗初发多发性骨髓瘤的临床观察

 目的 观察沙利度胺联合地塞米松治疗初发多发性骨髓瘤（MM）的疗效。方法 沙利度胺100 mg／d,每周增加50 ~ 100 mg／d,直到200 ~ 300 mg／d,维持治疗。地塞米松40 mg／d,第1 ~ 4天,第9 ~ 12天,第17 ~ 20天,28 d为1疗程。获完全缓解或部分缓解的患者,应用沙利度胺100 ~ 200 mg／d维持,每2个月应用地塞米松40 mg／d,第1 ~ 4天,冲击治疗1次。结果 21例初发MM 5例达完全缓解,12例获部分缓解,总有效率80.9 %。结论 沙利度胺联合地塞米松治疗初发MM疗效较好     

小剂量沙利度胺联合地塞米松治疗多发性骨髓瘤临床观察

 目的　观察小剂量沙利度胺联合地塞米松治疗多发性骨髓瘤（MM）的临床疗效及其不良反应。方法　12例MM患者,其中包括9例难治复发和3例初发,沙利度胺100～200 mg／d口服,每28 d为1个周期, 共3个周期,同时联合小剂量地塞米松15 mg／d口服,第1天至第4天,第15天至第18天,每28 d为1个周期,至少治疗3个周期。结果　CR 3例,PR 5例,进步3例,无效1例;不良反应可耐受,轻度便秘及嗜睡多见。结论　小剂量沙利度胺联合地塞米松治疗MM安全、有效,患者耐受性好。     

小剂量沙利度胺联合含单周地塞米松的VAD方案治疗多发性骨髓瘤42例

目的观察小剂量沙利度胺联合含单周地塞米松的VAD方案治疗多发性骨髓瘤（MM）的临床疗效及不良反应。方法给予42例MM患者小剂量沙利度胺（150～200）mg／d联合含单周地塞米松（40mg,口服,第1天至第4天）的VAD方案治疗,28d为1个疗程。4个疗程后进行总体评估。结果总有效率为80．95％（34／42）;其中完全缓解6例,部分缓解20例,进步8例,无效8例。不良反应轻微,患者治疗前后血红蛋白、骨髓浆细胞比例、β2微球蛋白、Karnofsky评分、血肌酐、血免疫球蛋白差异均有统计学意义（均P〈0．001）。结论小剂量沙利度胺联合含单周地塞米松的VAD方案治疗MM有效率高,不良反应轻微,值得临床进一步研究和推广应用。     

以亚砷酸为主的四联疗法治疗难治性多发性骨髓瘤11例

目的观察亚砷酸联合维生素C、沙利度胺、小剂量地塞米松治疗难治性多发性骨髓瘤（MM）的疗效及不良反应。方法11例难治性MM患者,应用0．1％亚砷酸注射液10mg／d加入5％葡萄糖注射液500ml静脉滴注,亚砷酸静脉滴注结束15min后,维生素C3．0g加入5％葡萄糖注射液500ml静脉滴注,沙利度胺100～150mg／d,睡前顿服,地塞米松1．5mg／d,晨起顿服。连用14～21d为1个疗程。结果显效3例;进步4例;2例病情相对稳定,2例无效,总有效率63．6％,患者无不能耐受的不良反应。结论亚砷酸联合维生素C、沙利度胺、小剂量地塞米松治疗难治性MM具有药效协同、不良反应减小、疗效较高、耐受性好等优点,值得临床深入研究和推广应用。     

沙利度胺联合地塞米松治疗难治复发性多发性骨髓瘤的临床研究

 目的 探讨沙利度胺联合地塞米松（Thal-Dex）方案治疗难治复发性多发性骨髓瘤（MM）的疗效及相关毒副作用。方法 采用Thal-Dex方案对15例难治复发性MM患者进行治疗，沙利度胺起始剂量为100 mg，维持两周后逐渐增至200 mg；地塞米松片40 mg口服，第1～4天、第9～12天、第17～20天，4周为1疗程；口服小剂量华法林（1.25 mg／d）预防深静脉血栓（DVT），监测骨髓细胞学浆细胞数、血M蛋白、血β2-微球蛋白及其他常规检查项目。结果 15例患者中完全缓解5例，部分缓解4例，微小反应4例，无反应1例，死亡1例，总体反应率为60.0 %；3例患者发生DVT；全部患者未发生Ⅱ级以上血液毒性。结论 Thal-Dex 方案对于难治复发性MM有较好的疗效，耐受性好，但需注意DVT发生。     

低剂量沙利度胺联合VAD方案治疗多发性骨髓瘤25例

 目的　探讨低剂量沙利度胺联合VAD方案治疗多发性骨髓瘤（MM）的疗效及不良反应。方法　确诊的MM患者25例，沙利度胺100 mg／d，每晚睡前口服；VAD方案：长春新碱0.5 mg／d静脉滴注，第1天至第4天，多柔比星10 mg／d静脉滴注，第1天至第4天，地塞米松40 mg／d口服，第1天至第4天、第9天至第12天、第17天至第20天，每月1个疗程，共6个疗程。结果　21例患者完成了6个疗程，完全缓解5例（23.8 %），部分缓解14例（66.7 %），未缓解2例（9.5 %），总有效率90.5 %。沙利度胺的主要不良反应为乏力、便秘、水肿、末梢神经炎，对症处理后可耐受。结论　低剂量沙利度胺联合VAD方案治疗MM有效率高，且不良反应较低。     

低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤35例

 目的　观察低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤（MM）患者的疗效及安全性。方法　35例初治及难治复发MM患者,硼替佐米1.1 mg／m2,第0、3、7、10天,静脉注射;沙利度胺从50 mg／d开始逐渐加量至150 mg／d或患者能够耐受的最大剂量;化疗方案根据每疗程患者情况选择MP、VAD或AD方案。28 d为1个疗程,每例患者至少接受2个疗程以上治疗。达到部分缓解（PR）及以上疗效的患者应用沙利度胺150 mg／d或患者能够耐受的最大剂量维持治疗。采用2006年MM国际统一疗效标准观察疗效,根据国际癌症研究中心不良事件通用命名标准评估不良反应。结果　中位随访20个月,35例患者治疗总有效率82.8 ％,其中完全缓解（CR）率48.6 %,良好的部分缓解（VGPR ）率17.1 %,PR率17.1 %。3年预计无进展生存（PFS）和总生存（OS）率分别为60.92 %和72.41 %。达PR以上疗效患者的OS率高于未达PR患者,差异有统计学意义（P＝0.004）。初治及难治复发患者客观缓解率（ORR）及OS率差异无统计学意义。Ⅲ～Ⅳ度非血液学毒性主要包括乏力（3／35）、恶心、呕吐（8／35）、便秘（4／35）和周围神经病变（3／35）。Ⅲ～Ⅳ度血液学毒性为粒细胞缺乏（10／35）和血小板减少（8／35）。结论　低剂量硼替佐米联合沙利度胺及化疗治疗MM具有较好的疗效及安全性,沙利度胺维持治疗可延长患者PFS时间。     

硼替佐米治疗难治性复发性多发性骨髓瘤疗效分析

 目的　探讨硼替佐米联合地塞米松治疗难治性复发性多发性骨髓瘤（MM）的临床疗效及不良反应。方法　硼替佐米1.3 mg／m2静脉注射第1、4、8、11天,地塞米松20 mg／d,第1天至第4天,第8天至第11天,第17天至第20天静脉滴注,21 d为1个周期,双周期时,地塞米松20 mg／d,第1天至第4天。结果　经4～6个周期治疗,3例完全缓解,4例接近完全缓解,3例部分缓解。结论　硼替佐米联合地塞米松治疗难治性复发性MM是较好的选择。     

地塞米松联合沙利度胺治疗14例多发性骨髓瘤疗效观察

目的：观察大剂量地塞米松联合沙利度胺治疗多发性骨髓瘤（multiplemyeloma，MM）的疗效及不良反应。方法：地塞米松20mg／d-40mg／d，奇数月d1-4，d9-12，d17-20，偶数月d1-4，28天／疗程，联合或不联合沙利度胺100mg／d-200mg／d。判断疗效，同时观察血常规、肾功能、Ca^2＋、影像学等变化。结果：14例患者的总有效率（CR＋PR＋进步）为85．71％，总缓解率（CR＋PR）57．14％（8／14例），初发患者中总有效率达100％（8／8例），总缓解率达75．00％（6／8例），复发难治患者中总有效率66．67％（4／6例），总缓解率33．33％（2／6例）。主要副作用为感染、血压升高、血糖升高。结论：大剂量地塞米松联合沙利度胺是治疗多发性骨髓瘤的有效方案，毒性较轻。     

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.