^153Sm—乙二胺四亚甲基膦酸对Walker256癌荷瘤大鼠骨侵袭骨溶解…

目的 研究＾１５３Ｓｍ－乙二胺四亚甲基膦酸（＾１５３Ｓｍ－ＥＤＴＭＰ）对荷瘤大鼠骨侵袭、骨溶解的抑制作用。方法 运用Ｘ线骨骼照片和胫骨病理切片,观察Ｗａｌｋｅｒ２５６癌大鼠模型的肿瘤骨侵袭和骨溶解情况。结果 荷瘤大鼠静脉注射＾１５３Ｓｍ－ＥＤＴＭＰ７４,１４８ＭＢｇ／ｋｇ后,遭受Ｗａｌｋｅｒ２５６癌侵袭及发生骨溶解的胫骨数减少近一半,３７ＭＢｇ／ｋｇ组对癌的骨侵袭和骨溶解仍有抑制作用。但各组大鼠的     

骨膦和（153）~Sm－EDTMP治疗骨转移癌

本文报道应用骨膦和／或１５３Ｓｍ－ＥＤＴＭＰ内照射治疗骨转移癌７４例。骨膦组２１例，１５３Ｓｍ－ＥＤＴＭＰ组２６例，对骨痛止痛有效率分别为８５．７％和８０．８％，对骨病变有效率分别为９．５％和１９．２％。而联合应用骨膦和１５３Ｓｍ－ＥＤＴＭＰ治疗３１例，止痛有效率和骨病变有效率分别为９３．５％和４５．２％，后者与前２组相比有显著差异（Ｐ＜０．０５）。三组毒副反应均少见。由此提示，骨膦＋１５３Ｓｍ－ＥＤＴＭＰ疗效显著，安全可靠，可能是当今治疗多发性骨转移癌的优选疗法。     

^153Sm—EDTMP治疗多发性骨转移癌

用１５３Ｓｍ－ＥＤＴＭＰ（ｅｔｈｙｌｅｎｅｄｉａｍｉｎｅｔｅｔｒａｍｅｔｈｙｌｅｎｅＰｈｏｓｐｈｏｎｉｃａｃｉｄ）治疗多发性骨转移癌６０例，其原发灶均经病理及细胞学证实。静脉一次给予量为１４．８～２９．６ＭＢｑ／ｋｇ体重，多数病人（５０／６０）按１８．５ＭＢｑ／ｋｇ体重计算治疗剂量，一般病人治疗１～４次，两次治疗间隔为４～８周。止痛有效率为８１．７％（４９／６０），给药前２周内９９ｍＴｃ－ＭＤＰ与给药后１５３Ｓｍ－ＥＤＴＭＰ全身骨显像进行观察比较。随访１～１２个月，认为１５３Ｓｍ－ＥＤＴＭＰ治疗多发性骨转移癌疗效好、副反应小，使用安全     

^153Sm—EDTMP对癌症骨痛治疗和提高生活质量的价值

应用＾１５３Ｓｍ－ＥＤＴＭＰ，治疗各种骨继发性肿瘤４０例。静脉一次给予量为２９．６ＭＢｑ／ｋｇ（０．８ｍＣｉ／ｋｇ），其中７例接受重复治疗。随访时间为３０天～１０个月。给药前２周内＾９９ｍＴｃ－ＭＤＰ与给药后＾１５３Ｓｍ－ＥＤＴＭＰ全身骨显象观察比较。该药副作用轻微，止痛效果显著。本组显效９例，有效２４例，总有效率为８２．５％，骨痛得到控制，生活质量明显提高。     

帕米膦酸二钠和^153Sm—EDTMP治疗骨继发性恶性肿瘤疗效对比 …

帕米膦酸二钠（ＡＰＤ）与＾１５３钐－乙二胺四甲基膦酸（１５３Ｓｍ－ＥＤＴＭＰ）皆为治疗骨继发性恶性肿瘤的较新药物，为比较两者的治疗效果，将４２例骨继发性患者随机分为ＡＰＤ组和＾１５３Ｓｍ－ＥＤＴＭＰ组每组各２１例，结果显示：ＡＰＤ和＾１５３Ｓｍ－ＥＤＴＭＰ组对患者骨痛缓解率分别为７６．１９％，９０．４８％（Ｐ〉０．０５），ＡＰＤ与＾１５３Ｓｍ－ＥＤＴＭＰ对骨转移灶控制率分别为４７．６２％，２３．８     

^153Sm—EDTMP治疗肿瘤骨转移止痛效果相关因素分析

目的 分析影响＾１５３Ｓｍ－ＥＤＴＭＰ对肿瘤转移性骨痛治疗效果的相关因素，方法 对我院近两年使用＾１５３Ｓｍ－ＥＤＴＭＰ行内照射治疗的５９例肿瘤转移性骨病人进行回顾性分析，按年龄，病灶数量，不同肿瘤分组，单次剂量给予＾１５３Ｓｍ－ＥＤＴＭＰ１８．５－３７ＭＢｑ／ｋｇ静脉注射，第２天行全身骨显像现查放射分布情况，建立随访。结果 总有效率为９３．６％，在年龄组中，以老年组效果最好，止痛有效率为９６．９     

帕米膦酸二钠和~(153)Sm-EDTMP治疗骨继发性恶性肿瘤疗效对比研究

帕米膦酸二钠（ＡＰＤ）与１５３钐－乙二胺四甲基膦酸（１５３Ｓｍ－ＥＤＴＭＰ）皆为治疗骨继发性恶性肿瘤的较新药物。为比较两者的治疗效果，将４２例骨继发性患者随机分为ＡＰＤ组和１５３Ｓｍ－ＥＤＴＭＰ组，每组各２１例，结果显示，ＡＰＤ和１５３Ｓｍ－ＥＤＴＭＰ组对患者骨痛缓解率分别为７６．１９％，９０．４８％（Ｐ＞０．０５）。ＡＰＤ与１５３Ｓｍ－ＥＤＴＭＰ对骨转移灶控制率分别为４７．６２％、２３．８１％（Ｐ＜０．０５）。说明ＡＰＤ对转移病灶控制的效果更佳。两种药物毒副作用不大，患者均可耐受。     

^153Sm—乙二胺四亚甲基磷酸盐治疗骨肿瘤转移性疼痛

本文介绍了一种新的肿瘤转移性疼痛治疗方法－＾１５３Ｓｍ－乙二胺四亚甲基磷酸盐（＾１５３Ｓｍ－ＥＤＴＭＰ）放射药物治疗法。＾１５３Ｓｍ－ＥＤＴＭＰ血液清除快，病变区骨摄取高，对正常组织及造血系统的毒副作用小。经临床近千例验证，＾１５３Ｓｍ－ＥＤＴＭＰ对肿瘤转移性骨痛的缓解率为７６％～９６％，治疗后转移灶完全消失占１０％。＾１５３Ｓｍ－ＥＤＴＭＰ治疗是临床常规治疗无效后缓解及治疗转移性骨痛的首选方法。     

^153Sm—EDTMP对鼻咽癌骨转移患者免疫状态影响的初探

１５３Ｓｍ－ＥＤＴＭＰ对鼻咽癌骨转移患者免疫状态影响的初探樊卫曾宗渊关键词鼻咽肿瘤骨转移瘤１５３Ｓｍ－ＥＤＴＭＰ核素治疗Ｔ细胞亚群中图号Ｒ７３９．６３Ｒ７３８．１钐－１５３乙二胺四甲撑膦酸（１５３Ｓｍ－ＥＤＴＭＰ）治疗鼻咽癌（ＮＰＣ）骨转移已成为一种...     

~（153）Sm─EDTMP对癌症骨痛治疗和提高生活质量的价值

应用１５３Ｓｍ─ＥＤＴＭＰ（ｅｔｈｙｌｅｎｅｄｉａｍｉｎｅｔｅｔｒａｍｅｔｈｙｌｅｎｔｐｈｏｓｐｈｏｎｉｃａｃｉｄ），治疗各种骨继发性肿瘤　　４０例。静脉一次给予量为２９．６ＭＢｑ／ｋｇ（０．８ｍＣｉ／ｋｇ），其中７例接受重复治疗。随访时间为３０天～１０个月。给药前２周内９９ｍＴｃ─ＭＤＰ与给药后１５３Ｓｍ─ＥＤＴＭＰ全身骨显象观察比较。该药副作用轻微，止痛效果显著。本组显效９例，有效２４例，总有效率为８２．５％，骨痛得到控制，生活质量明显提高。     

An experimental rat model of local bone cancer invasion and its responsiveness to ethane-1-hydroxy-1,1-bis(phosphonate)

Line A Walker carcinoma differs from line B in that it does not elicit hypercalcemia and hypercalciuria when implanted in rats at various sites (s.c, i.m., intraaortically). However, Walker 256/A, unlike line B, may invade the tibia when implanted i.m. in the adjacent gastrocnemius muscle. This invasion was evaluated by measuring the increased weight of the bone and decreased calcium concentration per unit weight of the tibia, by reduced opacity to X-ray, and by the presence of tumor cells in the compact bone cortex. Ethane-1-hydroxy-1,1-bis(phosphonate), a diphosphonate derivative, at a dose of 10 to 30 mg/kg/day s.c., prevented cancer cell invasion of the tibia as judged by the above criteria. This inhibition was obtained with no apparent effect on the growth of Walker 256/A carcinoma.     

Dose‐finding study of 153Sm‐EDTMP in patients with poor‐prognosis osteosarcoma

BACKGROUND:

Samarium‐153 ethylenediaminetetramethylene phosphonic acid (¹⁵³Sm‐EDTMP) has been used to treat patients with high‐risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of ¹⁵³Sm‐EDTMP that permits hematopoietic recovery within 6 weeks.

METHODS:

Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of ¹⁵³Sm‐EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de‐escalation with a target dose–limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm³ and a platelet count >75,000/mm³ within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions.

RESULTS:

The maximally tolerated dose of ¹⁵³Sm‐EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed.

CONCLUSIONS:

Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered ¹⁵³Sm‐EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high‐risk osteosarcoma. Cancer 2009. © 2009 American Cancer Society.     

Bone invasion by Walker 256 carcinoma, line A in young and adult rats: effects of etidronate

Line A of Walker 256 carcinoma implanted in the muscle adjacent to the tibia of young (6 weeks) and adult (9 months) male rats invaded the bone. Osteolysis and reactive growth were greater in the bone of young animals than in adults. Ethane-1-hydroxy-1, 1-bisphosphonate prevented bone lysis and tumor invasion of the cortex both in young and adult animals. This model may be useful for studies of age-related differences in tumor infiltration into the bone and for investigating drug effects on this process.     

帕米膦酸二钠联合153Sm-EDTMP对恶性肿瘤多发骨转移的疗效分析

目的 探讨帕米膦酸二钠（博宁）联合＾１５３Ｓｍ－ＥＤＴＭＰ对恶性肿瘤多发骨转移的临床疗效。方法 ３２例恶性肿瘤多发骨转移患者随机分为２组,每组１６例,分别接受＾１５３Ｓｍ－ＥＤＴＭＰ单独或与帕米膦酸二钠联合治疗。结果 联合组疼痛总缓解率（ＣＲ＋ＰＲ）为９３．８％,单用组为６２．５％,骨病灶控制总有效率（ＣＲ＋ＰＲ）联合组５６．３％,单用组为１８．８％,联合组疗效优于单用组（Ｐ〈０．０５）,两组均无     

153Sm-EDTMP治疗多发性骨转移癌的疗效分析

目的：评价＾１５３Ｓｍ－ＥＤＴＭＰ对多发性骨转移癌的止痛效果及消作用。方法：首次静脉给药剂量为３７ＭＢｑ／ｋｇ。重复治疗剂量，结合患者病情、病灶数、血象等的情增减。３次为一个疗程，给药间隔平均６周。结果：１５６例骨转移患者，骨痛完全缓痛５２例（３３．３％），部分缓解８１例（５１．９％），无效２３例（２１．２％）。止痛有效率为８５．２％（１３３／１５６），７２例骨转移患者治疗后，病灶骨／全身骨放射睡     

全身骨显像疗效评价^153钐-EDTMP治疗骨转移癌的疗效

目的：通过骨显像评价^153钐-EDTMP治疗骨转移癌的效果，进而证实其抑制、消除转移灶作用。方法：对182例恶性肿瘤合并骨转移病人共进行560次^153钐-EDTMP治疗，治疗前后常规行骨显像检查。结果：^153钐-EDTMP治疗后疼痛总缓解率为88．46％（161／182），12．64％（23／182）病例发生严重白细胞减低。44．51％（81／182）病例骨转移灶缩小、消失。结论：^153钐-EDTMP是通过抑制、消除骨转移灶达到止痛的。骨显像能显示治疗后骨转移灶的变化。     

Zoledronic acid reduces bone loss and tumor growth in an orthotopic xenograft model of osteolytic oral squamous cell carcinoma

Squamous cell carcinoma (SCC) is the most common form of oral cancer. Destruction and invasion of mandibular and maxillary bone frequently occurs and contributes to morbidity and mortality. We hypothesized that the bisphosphonate drug zoledronic acid (ZOL) would inhibit tumor-induced osteolysis and reduce tumor growth and invasion in a murine xenograft model of bone-invasive oral SCC (OSCC) derived from an osteolytic feline OSCC. Luciferase-expressing OSCC cells (SCCF2Luc) were injected into the perimaxillary subgingiva of nude mice, which were then treated with 100 μg/kg ZOL or vehicle. ZOL treatment reduced tumor growth and prevented loss of bone volume and surface area but had no effect on tumor invasion. Effects on bone were associated with reduced osteolysis and increased periosteal new bone formation. ZOL-mediated inhibition of tumor-induced osteolysis was characterized by reduced numbers of tartrate-resistant acid phosphatase-positive osteoclasts at the tumor-bone interface, where it was associated with osteoclast vacuolar degeneration. The ratio of eroded to total bone surface was not affected by treatment, arguing that ZOL-mediated inhibition of osteolysis was independent of effects on osteoclast activation or initiation of bone resorption. In summary, our results establish that ZOL can reduce OSCC-induced osteolysis and may be valuable as an adjuvant therapy in OSCC to preserve mandibular and maxillary bone volume and function.     

Walker 256/B malignant breast cancer cells improve femur angioarchitecture and disrupt hematological parameters in a rat model of tumor osteolysis

This study was designed to assess femur angioarchitecture and hematological effects of Walker 256/B cells in a rat model of tumor osteolysis. Tumor osteolysis was induced by in situ inoculation of Walker 256/B malignant cells. Six other rats were sham operated and served as control. Twenty days later, rats were euthanized, and femurs were collected than radiographed. Angioarchitecture [mean lumen diameter (MLD), wall thickness (WTh), Vessel number, volume, and separation (VNb, VV, and VSp respectively)] was studied by histomorphometry at 2 different positions (P1: diaphysis, and P2: metaphysis) of the operated femora. Some hematological parameters were also assessed. Walker 256/B induced marked tumor osteolysis, with cortical perforation and trabecular destruction, associated increase in bone vascularization (increases of VNb and VV and decrease of VSp). Angioarchitecture of W256/B rats was disorganized and showed large MLD and lower WTh. These effects were more prominent in P2. When compared to Sham group, significantly decreases at levels of red blood cell (RBC), hemoglobin (Hb), hematocrit (Ht), and white blood cell (WBC) were observed in W256/B rats. These results suggest that Walker 256/B cells induced tumor osteolysis, improve hypervasculature especially near the tumoral foci (P2) associated hematological disruption. Besides, tumor vessels showed abnormal (enlarged and thinner) and disorganized morphology.