伊班膦酸钠及其在肿瘤相关疾病中的应用

伊班膦酸钠系第三代含氮双膦酸盐药物，能强效抑制破骨细胞活性并诱导破骨细胞凋亡；能抑制肿瘤细胞分泌产生基质金属蛋白酶、血管内皮生长因子等活性物质，抑制骨溶解过程；能抑制乳腺癌细胞、前列腺癌细胞和骨髓瘤细胞对骨质的粘附和侵袭作用，并诱导上述肿瘤细胞凋亡，防止肿瘤骨转移；能防止骨质丢失，并通过对骨的二次性矿化作用．显著增加骨密度和改善骨的机械特性，用于预防和治疗骨质疏松症等。现综述近年来伊班膦酸钠的基础研究及其在肿瘤相关疾病中的临床应用。     

唑来膦酸在乳腺癌辅助治疗中的作用及其机制

双膦酸盐是治疗恶性肿瘤骨转移的有效药物之一,其作用机制是抑制破骨细胞介导的骨质重吸收.最新研究发现,新一代的双膦酸盐唑来膦酸可以诱导肿瘤细胞凋亡和抑制肿瘤血管新生,从而发挥直接或间接的抗肿瘤作用.有研究发现,对乳腺癌采用常用化疗药物序贯唑来膦酸治疗,可发挥协同抗肿瘤效应.唑来膦酸-弗隆辅助协同试验(Zometa-Femara Adjuvant Synergy Trial, ZO-FAST)和奥地利乳腺癌和结直肠癌研究小组-12(Austrian Breast and Colorectal Cancer Study Group-12, ABCSG-12)的最新研究结果显示,唑来膦酸在辅助治疗中与内分泌药物联用可显著提高患者的无病生存率和总生存率,而与辅助化疗联合使用的效果还有待唑来膦酸联合新辅助化疗降低复发(Neo-Adjuvant Zoledronic Acid to Reduce Recurrence,AZURE)临床试验予以证实.这些结果均表明,唑来膦酸用于乳腺癌的辅助治疗可以降低肿瘤的复发和转移.对唑来膦酸的最佳剂量和疗程尚有待进一步的研究予以确认.     

双膦酸盐在恶性肿瘤治疗中的作用研究进展

双膦酸盐类药物(BPs)在恶性肿瘤的治疗中发挥着越来越重要的作用。文章对BPs在防治骨转移、预防及推迟骨相关事件发生、防治肿瘤治疗相关性骨丢失(CTIBL)及其直接和间接抗肿瘤作用等方面文献进行综述,以提高对BPs在恶性肿瘤治疗中作用的认识。     

伊班膦酸钠与唑来膦酸对骨肿瘤患者的疗效比较

目的探讨唑来膦酸与伊班膦酸钠对骨肿瘤患者的疗效影响。方法选取2015年8月至2016年8月间山东单县海吉亚医院收治的104例骨肿瘤患者,采用随机数字表法分为观察组与对照组,每组52例。观察组采用伊班膦酸钠治疗,对照组采用唑来膦酸治疗,比较两组患者的疼痛治疗效果、不良反应和生活质量。结果治疗后观察组患者视觉模拟评分为(4.3±1.5)分,显著低于对照组的(6.0±1.6)分;观察组患者不良反应发生率为9.6%,低于对照组的26.9%;观察组患者Kamofsky评分为(58.5±8.5)分,显著高于对照组的(48.5±7.5)分;观察组患者药物治疗费用为(2025.5±70.5)元,显著低于对照组的(4052.5±80.5)元,以上两组比较,差异均有统计学意义(均P<0.05)。结论相比唑来膦酸,伊班膦酸钠可有效降低骨肿瘤患者的疼痛阈值,提高生活质量,不良反应少,治疗费用低。     

伊班膦酸钠治疗恶性肿瘤骨转移48例

目的观察恶性肿瘤骨转移患者应用伊班膦酸钠治疗后的病灶及临床症状缓解情况。方法采用开放、无对照的研究方法，48例患者第一周期连续静脉滴注3d伊班膦酸钠6mg，以后6mg／4周一次。结果骨转移病灶总有效率为47．92％；骨痛在第3、14天及2周期后的总有效率分别为68．75％、79．17％、72．92％，表现为波峰趋势，但无统计学意义（P〉0．05），治疗后高钙血症恢复正常，活动能力明显改善。结论负荷剂量伊班膦酸钠可以快速缓解疼痛，效果稳定，患者不良反应轻，可显著改善患者的生存质量。     

伊班膦酸钠治疗肺癌骨转移的临床研究

背景与目的: 骨骼是肺痛最常见的转移部位.骨转移的并发症如疼痛、功能障碍不仅会降低患者的生活质量,甚至会加快患者的死亡.基于上述情况,本文探讨伊班膦酸钠联合化疗治疗肺痛骨转移的临床作用.方法: 2006年6月-2007年6月共收治肿痛骨转移患者64例,随机分为两组:伊班膦酸钠联合化疗组和单纯化疗对照组.对比两组的疼痛缓解率、血清AKP、Ca2 和Scr的变化.结果: 研究组骨骼疼痛较对照组有明显缓解(有效率71.1%比42.3%)(P=0.006):研究组治疗后血清AKP和Ca<'2 >较治疗前有明显下降(P＜0.05);两组患者血清肌苷在治疗前后无明显改变(P＞0.05).结论: 伊班膦酸钠是安全、低毒性药物,其联合化疗有缓解肺癌骨转移疼痛和抑制骨转移的作用.     

伊班膦酸钠联合放化疗改善乳腺癌骨转移患者生活质量的临床研究

目的探讨伊班膦酸钠与放化疗联合治疗乳腺癌骨转移的作用及对患者生活质量的影响.方法 2001年3月至2003年3月泰山医学院附属医院肿瘤中心收治乳腺癌骨转移患者67例,随机分为伊班膦酸钠联合局部放疗及全身化疗研究组,单纯化疗或放疗对照组,对比两组临床缓解率、Karnofsky评分及生活质量评分结果,并做统计学分析.结果研究组总有效率84.8%,完全缓解率33.3%,部分缓解率51.5%,病灶稳定率6.1%,恶化9.1%;对照组依次为55.9%、23.6%、29.4%、23.5%和20.6%,两组比较差异有显著性(P<0.05);两组疼痛缓解中位时间分别为3和5 d;功能障碍缓解率分别为84.0%和78.3%,两组比较差异无显著性(P>0.05).Karnofsky评分增加率分别为72.7%和52.9%,两组比较差异有显著性(P<0.01).结论伊班膦酸钠注射液可提高患者生活质量、缓解骨转移性疼痛、延长生存期,尤其是同时联合放化疗能够尽快地减轻疼痛,提高乳腺癌骨转移患者的生活质量,是治疗乳腺癌骨转移并提高生活质量的较好的综合治疗方案.     

伊班膦酸钠治疗141例恶性肿瘤骨痛的随机双盲对照临床研究

目的：评价国产伊班膦酸钠（Ibandronate）治疗恶性肿瘤骨痛的疗效和不良反应方法：采用随机双盲阳性药物对照临床研究方法，将骨痛患者随机分为静脉滴注伊班膦酸钠4rag（A组68例）、静脉滴注帕米膦酸二钠60mg（B组73例）．观察3周内骨痛变化和不良反应结果：141例患者入组，可评价疗效136例A组治疗有效率为72．3％（47／65），B组为63．4％（45／71），两组间无统计学差异。两组不良反应类似。结论：伊班膦酸钠注射液治疗恶性肿瘤骨转移疼痛疗效确切，与帕米膦酸二钠相比疗效和不良反应相似．     

Ibandronate: its role in metastatic breast cancer

Bisphosphonates are the most effective agents for treating and/or preventing complications of bone metastases and are the standard of care in this setting. Currently, four bisphosphonates are available for metastatic bone disease (MBD): clodronate, pamidronate, zoledronic acid, and ibandronate. Although all four of these bisphosphonates have been shown to reduce the incidence of skeletal-related events in patients with bone metastases, there are substantial differences among these agents in their potency, dose and route of administration, and side effects. Ibandronate and zoledronic acid, the two newer aminobisphosphonates, appear to have similar biochemical efficacies when phase III trial data are compared. Both agents were equally effective in reducing markers of bone resorption in the only prospective comparative trial carried out to date, but no data on relative clinical efficacy are available from head-to-head comparisons. Both the oral and i.v. formulations of ibandronate have also shown long-term efficacy in managing metastatic bone pain (MBP), but the onset of action of standard bisphosphonate treatment is not sufficient when rapid relief of pain is required. Because of its favorable renal safety profile, i.v. ibandronate can be administered daily for 3 days, as a so-called "loading dose." This dosing regimen has allowed rapid and effective relief of MBP without the unwanted side effects associated with opioids and other analgesics. Ibandronate is thus an effective, flexible, and well-tolerated bisphosphonate that can meet the varying requirements of patients with MBD.     

血液系统疾病基因组学分析及临床应用进展

随着分析成本的下降和分析能力的增加,基因组学分析在疾病研究和应用中的报道迅速增多,为医学检验带来了从"目标检测"到"目标分析"的革新性进展.文章结合近年来的研究进展及第59届美国血液学会(ASH)年会相关报道,对基因组学分析在血液系统疾病中的应用前景进行介绍.     

Ibandronate: its pharmacology and clinical efficacy in the management of tumor-induced hypercalcemia and metastatic bone disease

It is well accepted that tumor cells in the bone, especially from breast cancer, prostate cancer and multiple myeloma, can stimulate osteoclast formation and activity. Bisphosphonates are potent inhibitors of osteoclast-mediated normal and pathologic bone resorption. Besides their apoptotic and antiproliferative activity on osteoclasts, bisphosphonates can also exert similar effects on macrophages and tumor cells. Currently, it is unknown if this effect can be translated into clinical practice with regard to an effective adjuvant therapeutic regimen for high-risk patients with systemic recurrences following primary treatment of a given cancer. There are several new aspects that might extend the clinical use of ibandronate, a bisphosphate, in oncology: prevention of hypogonadal osteoporosis in men, palliative management of painful osseous metastases and adjuvant therapy of high-risk prostate cancer patients. Safety and tolerability are excellent for the oral and intravenous formulations, and ibandronate can even be safely applied in pre-existing renal insufficiency. The purpose of this review is to critically reflect the pharmacology and clinical efficacy of ibandronate in the management of tumor-induced hypercalcemia, osteoporosis and metastatic bone disease.     

Ibandronate: its pharmacology and clinical efficacy in the management of tumor-induced hypercalcemia and metastatic bone disease

It is well accepted that tumor cells in the bone, especially from breast cancer, prostate cancer and multiple myeloma, can stimulate osteoclast formation and activity. Bisphosphonates are potent inhibitors of osteoclast-mediated normal and pathologic bone resorption. Besides their apoptotic and antiproliferative activity on osteoclasts, bisphosphonates can also exert similar effects on macrophages and tumor cells. Currently, it is unknown if this effect can be translated into clinical practice with regard to an effective adjuvant therapeutic regimen for high-risk patients with systemic recurrences following primary treatment of a given cancer. There are several new aspects that might extend the clinical use of ibandronate, a bisphosphate, in oncology: prevention of hypogonadal osteoporosis in men, palliative management of painful osseous metastases and adjuvant therapy of high-risk prostate cancer patients. Safety and tolerability are excellent for the oral and intravenous formulations, and ibandronate can even be safely applied in pre-existing renal insufficiency. The purpose of this review is to critically reflect the pharmacology and clinical efficacy of ibandronate in the management of tumor-induced hypercalcemia, osteoporosis and metastatic bone disease.     

SURVIVIN基因与肿瘤相关研究进展

survivin作为凋亡抑制蛋白家族中独特一员,参与细胞的分裂和增殖过程调节,在细胞凋亡抑制中起重要作用.鉴于组织分布的特点及与多数肿瘤相对关联性,其研究为肿瘤临床诊断、治疗提供了有力支持.survivin可以作为较好的肿瘤靶向治疗基因,肿瘤的突破很可能是基因水平的突破,因此survivin的进一步研究可能为肿瘤治疗研究扫清障碍.     

恶性肿瘤相关凝血功能紊乱与抗凝治疗

凝血功能紊乱与恶性肿瘤之间相互影响、相互促进,最终形成一个严重影响肿瘤患者预后的恶性循环.凝血功能紊乱与恶性肿瘤相互作用关系的日趋明朗使抗凝成为肿瘤治疗的一个新的突破口.大量实验室及临床研究显示,抗凝治疗能抑制肿瘤发生、发展,改善肿瘤患者的预后.但针对不同患者、不同种类的抗凝剂,抗凝治疗的有效性及安全性尚有待进一步深入的研究.     

Myeloid-derived suppressor cell role in tumor-related inflammation

Chronic inflammatory state can create a proper environment for neoplastic onset and sustain cancer growth. The inflammatory state that arises at the tumor edge could contribute to immune escape phenomena in many ways. Myeloid-derived suppressor cells (MDSCs), a cell population that contributes to tumor escape, immune tolerance, and suppression, respond to a variety of pro-inflammatory and anti-inflammatory stimuli, which drive their recruitment and activation. Understanding how the inflammatory milieu favours tumor escape through the accumulation of MDSCs could be very useful to improve the efficacy of cancer immunotherapy.     

Burkitt's lymphoma: its clinical course in relation to immunologic reactivities to Epstein-Barr virus and tumor-related antigens.

In 141 patients with African Burkitt's lymphoma, the relationship between Epstein-Barr virus (EBV)-related antibody titers and the clinical course of this disease was presented. Antiviral capsid antigen tests gave positive results in all patients, siblings, and control neighbors; but the geometric mean antibody titers to viral capsid antigen were significantly higher in patients than in siblings or neighbors (P less than 0.001). No control neighbors or siblings had antibodies to restricted (EA-R) or diffuse (EA-D) early antigen. Mean geometric anti-EA-R titers at admssion and at last visit were significantly lower in patients with stage (I and II) than in those with stage (III and IV) disease; this most likely reflected the degree of tumor burden. Patients who relapsed after 1 year of sustained remission had significantly higher anti-EA-R titers than did those who did not. The increase in the probability of relapse was sixfold for those patients with an anti-EA-R titer of greater than 160 after 1 year of sustained remission. Survivors and nonsurvivors differed significantly in the final EA-R and Epstein-Barr virus nuclear antigen (EBNA) titers (P less than 0.05 and P less than 0.001, respectively). Anti-EA-D titers were particularly likely to be positive in patients with multiple relapses. When skin reactivity to an antigen from RAJI cells was compared to EBV-related serologic reactions in the same patient, a significant inverse correlation (P less than 0.001) between skin reactivity and EBNA titers appeared. Pretreatment sera from patients with high EBNA titers did not block skin reactivity to the RAJI antigen.     

A comparison of tumor-related antigens in male and female breast cancer

Summary A retrospective analysis was undertaken in which 15 female and 15 male breast cancers were matched by age, stage, estrogen receptor status, and histologic type. Our protocol compares male and female breast cancers for reactivity with antibodies against tumor-associated antigens known to be present on female breast cancer cells. Formalin-fixed sections of each primary tumor were reacted in the ABC immunoperoxidase assay against antibodies B72.3 and DF.3 and an antibody to theras p21 antigen. Reactivity to B72.3 and DF.3 was similar. However, the ras p21 antigen was expressed to a significantly greater extent in female breast cancers (p = .0008). Thus, although there are similarities in antigenic phenotype of male and female breast cancers, some female breast cancers may have a different pathogenesis as demonstrated by increased amounts of a specific oncogene product.