骨计量学方法在骨质疏松模型中的定量观察

目的观察骨结构与骨质疏松关系即骨构筑学的定量测量"骨质量"的价值,探讨骨组织形态计量学与μCT三维重建计量方法的价值意义。方法采用30只SD雌性大鼠,分成假手术组、切除卵巢去势组和去势后服用阿伦膦酸钠组,每组10只。在服药100 d后处死,进行全股骨骨密度测量及股骨下端不脱钙切片的骨计量学观察。三维重建采用美国GE公司eXplore Locus SP型μCT,用Micview V2.1.2重建软件选取股骨下端骨骺板下2 mm3兴趣窗进行结构计量测量。结果去势后骨体积密度显著性下降,由假手术组的(53.00±3.20)%降至(19.16±2.97)%(P<0.001);经二膦酸盐治疗后得到显著性改善(升至(40.40±3.07)%,与去势组比较P<0.001)。同时假手术组与去势组和去势组与二膦酸盐组之间,骨计量学指标中四环素标记率,类骨质的表面密度、平均类骨质表面厚度及动态指标,骨矿化沉积率与骨矿化延迟时间等均有显著性差异(P<0.05)。μCT结果显示骨小梁体积比与骨表面积体积比显示结果同骨计量学结果相似,数值均同比例减少。另外在三维结构计量上,除骨小梁厚度外,骨小梁数目、骨小梁间隙等均出现显著性变化。结论骨组织形态计量学与显微CT三维重建定量分析对骨结构与骨质量指标均能进行定性、定量的客观评价;骨计量学方法能从静态和动态两个方面反映骨新陈代谢过程,可以精确地反映出骨重建过程的变化规律和特点。     

早期预防性治疗对绝经后骨质疏松症影响的动物实验研究

目的评价早期预防性抗骨吸收治疗对绝经后骨质疏松症骨量、骨代谢指标和骨组织形态的变化特点,提供早期监测和预防绝经后骨质疏松症的依据.方法以去卵巢大鼠为实验对象、抑制骨吸收的唑来膦酸注射液为赋形药物,建立绝经后骨质疏松症的动物模型.选取44只3个月龄雌性SD大鼠,除假手术组行假手术外,其余各组均行双侧卵巢切除.假手术组(sham)、去势对照组(ovx)以安慰剂处理,其余两组分别在去势后3d、1个月给予唑来膦酸注射液(zoledronic acid,ZOL) 500μg/kg静脉单次注射,分别在实验开始、术后1个月及术后3个月测定大鼠股骨骨密度(BMD),收集血清测定I型前胶原氨基端前肽(PINP)、抗酒石酸酸性磷酸酶5b (TRACP-5b)的值变化,并光镜下观察大鼠股骨病理学变化,图像分析系统观察骨形态计量学静态指标骨小梁面积百分率(TBV)、骨小梁厚度(Tb.Th)、骨小梁间距(Tb.sp)的变化.结果应用去卵巢大鼠成功建立绝经后骨质疏松模型.去势对照组在1个月股骨BMD、血清PINP和TRACP-5b、TBV、Tb.Th及Tb.sp等指标变化上和正常对照组存在显著性差异(P＜0.01);去势3d即行ZOL治疗者和假手术对照组的BMD、骨代谢、骨形态学指标比较变化无显著性差异(P＞0.05);1个月后开始ZOL治疗者仅部分恢复骨密度,血清PINP、TRACP5b、骨组织形态指标变化和早期治疗组比较存在非常显著性差异(P＜0.01),且其骨小梁连接有明显的退变.结论骨代谢指标可用于抗骨吸收治疗的疗效监测;去势大鼠早期进行预防性抗骨吸收治疗,能抑制其骨量的丢失,减慢骨小梁退变,恢复骨密度.     

雌激素对骨质疏松性骨折愈合影响的实验研究

目的研究雌激素对大鼠骨质疏松性骨折愈合的影响。方法选择6月龄雌性SD大鼠60只,随机分为雌激素组、对照组（骨质疏松组）及假手术组,每组20只,前二组建立去卵巢大鼠骨质疏松性骨折模型,假手术组暴露卵巢而不切除,术后3个月行右侧股骨中段骨折内固定术。前二组术后分别皮下注射苯甲酸雌二醇及等量生理盐水,进行骨密度、X线片、组织病理学和生物力学检测,观察骨折愈合的情况。结果雌激素组骨折局部骨密度、生物力学性能明显高于对照组,差异有统计学意义（P〈0．05）;雌激素组比同时期的对照组骨痂生成量多。结论雌激素在促进骨质疏松性骨折愈合时能增加骨量,同时能提高骨生物力学特性和抗骨折能力。     

131I-EGF显像对肺癌荷瘤裸鼠化疗疗效的评价

目的探讨131I-EGF动态显像技术对肺癌倚瘤裸鼠化疗疗效的评价。方法将肺癌细胞株A549种植到BALB／cA—nil裸鼠体内,待移植瘤长至直径0．8～1．2cm时,随机分为4组：空白对照组、实验组（紫杉醇组、顺铂组和联合化疗组）。空白对照组腹腔注射0．1ml生理盐水;紫杉醇组腹腔注射紫杉醇5mg／kg;顺铂组腹腔注射ill@34rag／kg;联合化疗组腹腔注射紫杉醇5mg／kg和顺铂4mg／kg。裸鼠化疗后分别丁即刻和第7、14、21及28犬注射131I-EGF0．5h后开始显像,勾画感兴趣区（ROI）,计算肿瘤／健侧对应部位放射性（T／NT）比值,并测量肿瘤体积。第28天完成显像后,处死裸鼠,测量肿瘤／血液及肿瘤／肌肉放射性比值,计算抑瘤率和131I-EGF的生物学分布。结果肿瘤组织吸收131I-EGF较多,肿瘤／肌肉放射性比值对照组为5．65,高于联合化疗组（1．55,t=9．829,P〈0．01）、紫杉醇组（1．14,t=12．636,P〈0．01）和顺铂组（0．99,t=12．313,P〈0．01）。肿瘤／血液放射性比值对照组为3．15,高于联合化疗组（0．76,t=3．384,P〈0．05）、紫杉醇组（1．22,t=2．826,P〈0．05）和顺铂组（1．22,t=2．713,P〈0．05）。131I-EGF可使肿瘤组织清晰显像,联合化疗组肿瘤体积401．9mm3,与对照组（1134．2mm3）差异有统计学意义（t=9．393,P〈0．01）;紫杉醇组肿瘤体积634．73mm3（t=7．140,P〈0．01）,顺铂组肿瘤体积700．7mm3（t=6．820,P〈O．01）,这2组与对照组差异有统计学意义。各化疗组与对照组间T／NT比值差异有统计学意义（F=1011．251,P〈0．01）。结论化疗效果好的肿瘤,131I-EGF显像示肿瘤体积较小,瘤体内放射性分布较少;而化疗效果差的肿瘤体积逐渐增大,瘤体内放射性分布较多。131I-EGF显像可用于指导倚瘤裸鼠的化疗。     

Rb2／p130基因在骨肉瘤中的表达及临床意义

目的：研究骨肉瘤中Rb2／p130基因表达情况及其在骨肉瘤发生发展中的作用。方法：用免疫组织化学S—P法检测Rb2／p130基因在62例骨肉瘤、39例骨软骨瘤及51例非肿瘤患者正常骨组织中的蛋白表达情况,采用SPSS11．0统计学软件包对实验结果进行统计学分析。结果：骨肉瘤组中pRb2／p130阳性率为27．42％,骨软骨瘤组阳性率为76．92％,正常骨组织阳性率为82．35％,骨肉瘤组与骨软骨瘤组及正常骨组织组中Rb2／p130基因表达差异均有统计学意义（P〈0．01）。结论：Rb2／p130基因在骨肉瘤中以低表达方式存在,它与骨肉瘤的发生、发展及预后关系密切,并且有可能因其低表达而促使骨肉瘤的发生、发展,其机理有待进一步研究。     

HCE方案一线治疗小细胞肺癌的临床观察

背景与目的 化疗是小细胞肺癌的主要治疗方法。本研究拟探讨羟基喜树碱联合依托泊苷、卡铂组成的HCE方案治疗小细胞肺癌的临床疗效和耐受性。方法 将初治小细胞肺癌患者随机分入HCE方案和依托泊苷联合顺铂（EP）方案组，比较两组的临床疗效和毒副反应。结果 HCE组中评价疗效者31例，完全缓解率为54．8％（17／31），总有效率为90．3％（28／31）；EP组40例，完全缓解率为22．5％（9／40），总有效率为70．0％（28／40），两组完全缓解率比较有显著性差异（P〈0．01）。两组中位疾病进展时间分别为6个月及10个月（P〈0．05）；1年生存率分别为72．4％、69．4％（P〉0．05），2年生存率分别为51．7％、44．4％（P〈0．05），3年生存率分别为40．0％、29．2％（P〈0．05）；中位生存期分别为11．5个月及25个月（P〈0．05）；两组的主要不良反应为骨髓抑制及胃肠道反应，HCE组骨髓抑制及肝功异常发生率高于EP组，但无显著性差异（P〉0．05），胃肠道反应显著低于EP组（P〈0．01）。结论 HCE方案治疗小细胞肺癌疗效肯定，完全缓解率高，毒副作用轻，值得进一步推广。     

中晚期前列腺癌PET／CT定位三维适形放疗的疗效和预后分析

目的：探讨中晚期前列腺癌经18^FDGPET／CT定位适形放疗的疗效、副反应及失败原因。方法：对68例中晚期前列腺癌患者随机分为18^FDGPETYCT定位适形放疗组（PET／CT组）和普通CT定位适形放疗组（普通CT组）。PET／CT组用PET／CT扫描定位,将扫描数据输入三维治疗计划系统,将PET图像和CT图像融合后进行靶区（GTV与PrrV）和重要脏器勾画、三维重建,制定计划后常规分割适形放疗40Gy左右,然后缩野放疗至总剂量60Gy～70Gy;普通cT组用普通CT定位设野,三维适形放疗至相同剂量。结果：PET／CT组的平均刚体积、膀胱V40、直肠V40均小于普通cT组（P均〈0．01）;两组放疗后PSA均明显下降（P均〈0．01）;PET／CT组的中位复发时间12．1个月,普通CT组的中位复发时间9．2个月,两者差异有统计学意义（P〈0．01）;PET／CT组的胃肠道与膀胱放射性副反应低于普通CT组（P均〈0．05）;疗前GTV≤50cm^3者预后好。结论：PET／CT定位三维适形放疗中晚期前列腺癌可以优化放疗计划,减少放射副反应,分期早的病变预后好。     

BMP2、IL-6在骨的纤维结构不良中的表达及临床意义

目的了解骨的纤维结构不良（FD）中骨形态发生蛋白2（BMP2）、白细胞介素6（IL-6）的表达情况，探讨它们在FD发病中的作用，为进一步研究及合理地治疗FD提供实验依据。方法通过免疫组化方法对39例FD患者病理标本中BMP2、IL-6的表达水平进行检测。与10例正常骨组织和20例骨化性纤维瘤（OFD）病理标本作对照。结果FD、OFD和正常骨标本中均可见BMP2阳性染色，但BMP，在FD病变组织中表达程度高于对照组（P〈0．01）；正常骨标本切片中未见IL-6阳性染色，而在FD中均可见IL-6广泛阳性染色，部分OFD呈阳性染色，FD组与两对照组比较组间差异有显著性意义（P〈0．01）。结论FD形成可能与诱导成骨因子调节紊乱有关。IL-6是FD形成的重要生物因子，临床使用二磷酸盐、糖皮质激素治疗FD和McCune—Albright综合征有效。     

急性白血病细胞P-gp LRP的表达及其临床意义

目的：研究急性白血痛细胞P-糖蛋白（P—gp）、肺耐药蛋白（LRP）的表达情况，观察其表达率与临床症状及化疗缓解率的关系。方法：利用P—gp、LRP单克隆抗体，采用流式细胞技术分别测定15例正常对照和79例急性白血病（AL）患者P-gp、LRP的表达率，分析两种蛋白表达的临床意义。结果：初治急性淋巴细胞白血病（ALL）组P—gp、LRP的表达率均高于初治急性髓细胞白血病（AML）组（P〈0．01），复发／难治ALL组P—gp的表达率与复发／难治AML组相比无显著性差异（P〉0．05），而LRP的表达率较复发／难治AML组的表达率高（P〈0．01）。复发／难治组P—gp、LRP的表达率均高于相应的初治组（P〈0．05）。急性白血病患者P—gp、LRP的表达之间无相关性（L=0．0746，P〉0．05）。急性白血病细胞P—gp^＋／LRP^＋组缓解率低于P—gp^＋／LRP^-、P—gp^-／LRP^＋组（P〈0．05），并明显低于P—gp^-／LRP^-组（P〈0．01）。结论：复发／难治组P—gp、LRP的表达率高于初治组，而两者的表达率无相关性。P—gp、LRP表达阳性的患者缓解率低，且易出现髓外浸润。同时检测P—gp、LRP的表达较单独检测一种蛋白更具有临床意义。     

多肿瘤标志物蛋白芯片检测系统在肺癌诊断中的应用价值

目的：探讨多肿瘤标志物蛋白芯片检测系统对肺癌的诊断价值。方法：用该系统测定128例肺癌患者，26例肺良性病变患者血清中12种肿瘤标志物（CA199，NSE，CEA，CA242，CA125，CA153，AFP，ferritin，free—PSA，PSA，β-HCG及HGH）的水平。结果：肺癌组的芯片阳性率为82％（105／128），显著高于肺良性病组（15．38％，4／26）（P〈0．01）；肺癌不同分期组间阳性率存在显著性差异，以Ⅳ期肺癌组阳性率最高为79．28％（P〈0．01），不同分期之间CA199、CEA以及CA242血清水平存在显著性差异（P〈0．01）；不同病理类型肺癌组间阳性率无显著性差异（P〉0．05）；CEA阳性率以腺癌组最高，但与其他组织学类型肺癌比较无显著差异（P〉0．05）；NSE阳性率以小细胞肺癌组最高（P〈0．01）；单项肿瘤标志物检测与多项肿瘤标志物蛋白芯片联合检测肺癌的阳性率有明显的差异（P〈0．01）。结论：多肿瘤标志物蛋白芯片的应用对肺癌的诊断及分期、病理类型及判断预后有一定的临床参考价值。     

Properties of bisphosphonates in the 13762 rat mammary carcinoma model of tumor-induced bone resorption.

Bone metastasis from primary tumors is a clinically important complication of neoplastic progression. The role of parathyroid hormone-related protein (PTHrP) and transforming growth factor (TGF)-beta1 in this process has been clearly established. The current study describes an in vivo model of 13762 rat mammary carcinoma tumor cell-induced osteolysis in which PTHrP and TGF-beta1 expression is observed. Exposure of in vitro-cultured 13762 cells to doxorubicin, cis-platinum, carboplatin, methotrexate, 5-fluorouracil, paclitaxel, alendronate, risedronate, or pamidronate for 72 h resulted in varying effects on cell proliferation (IC(50) values of 0.005, 0.4, 1.9, >40, 17.9, 0.003, >40, >40, and 33.6 micro M, respectively). Tumor cells were implanted into the intramedullary space of the proximal tibia of rats, and the time course of tumor progression was evaluated using radiographic and microcomputed tomography scanning techniques. Trabecular bone mineral density, cortical bone mineral density, and whole bone mineral density were measured (in mg/cm(3)). In untreated animals, radiographic evidence of osteolysis was evident 7 days after implantation. Trabecular bone mineral density and whole bone mineral density were significantly decreased by 21 days after implantation (48% and 26%, respectively). Bisphosphonates showed broad protective activity against tumor-driven osteolysis, Immunohistochemical evaluation of s.c. and intratibially implanted cells demonstrated the expression of PTHrP and TGF-beta1. The results of this study demonstrate the ability of 13762 rat mammary carcinoma cells to elicit a measurable osteolysis and that bisphosphonates inhibit the tumor-induced bone resorption in this model.     

The impact of zoledronic acid therapy in survival of lung cancer patients with bone metastasis

Bone metastases occur in 20–40% of patients with lung cancer. Recent studies demonstrate a direct antiproliferative effect of 3rd generation bisphosphonates (BPs) on lung tumors, which may influence the survival. Therefore, we examined the clinical impact of zoledronic acid (ZOL; Zometa®), a 3rd generation BP, with a focus on the survival, time to progression and pain effect in lung cancer patients with bone metastases. Lung cancer patients (n = 144, Stage IV) with evidence of metastasis bone scan were included. Eighty‐seven of 144 experienced bone pain and received ZOL, 4 mg i.v. every 21 days (Group A), whereas the other 57 patients received no ZOL (Group B). All patients were treated with a combination chemotherapy consisted of docetaxel 100 mg/m² and carboplatin AUC = 6. It was found that Group A had a statistically significant longer survival (p < 0.01) when compared to Group B. A statistically significant positive correlation was found between the number of cycles of therapy with ZOL and total patient survival (p < 0.01, Pearson correlation) and time to progression (p < 0.01). Pain effect of ZOL had no significant difference between the 2 groups of patients (p > 0.05). Urine N‐telopeptide of type I collagen (NTx) levels decreased in patients with NTx ≤ 29 nM BCE/mM creatinine at baseline after treatment with ZOL. The results of our study suggest that the addition of ZOL increases overall survival in lung cancer patients with bone metastases. The longer period of receiving ZOL, the better effect on survival and time to progression. © 2009 UICC     

High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation,local insulin-like growth factor release,and tumor associated macrophages

Background: The association between obesity and colorectal cancer (CRC) risk has been well established. This relationship appears to be more significant in men than in women, which may be attributable to sex hormones. However, controlled animal studies to substantiate these claims and the mechanisms involved are lacking.Materials and Methods: MC38 murine colon adenocarcinoma cells were injected subcutaneously into high-fat diet (HFD) fed male, female and ovariectomized (OVX) female C57BL/6 mice.Results: HFD increased tumor growth (main effect) that was consistent with metabolic perturbations (P < 0.01). HFD OVX mice exhibited the most significant tumor growth compared to HFD male and female mice (p < 0.05) and this was associated with increased subcutaneous adipose tissue (p < 0.05). Further, the subcutaneous adipose tissue depots within HFD OVX mice exhibited more severe macrophage associated inflammation compared to female (P < 0.01), but not male mice. Conditioned media from subcutaneous adipose tissue of HFD OVX contained higher IGF-1 levels compared to male (P < 0.01), but not female mice. Finally, HFD OVX mice had increased M2-like gene expression in their tumor-associated macrophages (TAMs) compared to female mice (P < 0.01).Conclusions: This work provides evidences suggesting adiposity, adipose specific IGF-1, macrophage associated adipose inflammation, and TAMs as potential mechanisms driving obesity-enhanced CRC in females lacking ovarian hormones.     

Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression in mice

Obese postmenopausal women have a 50% higher risk of breast cancer than non-obese women. There is not an animal model that mimics postmenopausal obesity related to breast cancer progression. Using age-relevant C57BL/6 mice, this study determined whether postmenopausal obesity increases VEGF expression, tumor angiogenesis, and breast tumor growth. Ovariectomy (OVX) was performed in 12 sixty week-old female mice, then followed by a low-fat (5%, LF, n=6) or a high-fat (60%, HF, n=6) diet for 12 weeks. In the eighth week of the dietary program, 10(6) E0771 (mouse breast cancer) cells were injected in the left fourth mammary gland. Tumor size was monitored for 4 weeks. Body weights were monitored weekly. At the end of the experiment, blood samples, visceral fat and tumors were collected for measuring VEGF expression using ELISA and intratumoral microvessel density (IMD) using CD31 immunochemistry. Body weight was significantly increased in OVX/HF mice, compared to OVX/LF group (55.3±1.7 vs. 41.5±1.5 g; p < 0.01). There was a two-fold increase in the ratio of visceral fat/BW in OVX/HF mice, compared to those in OVX/LF group (0.062±0.005 vs. 0.032±0.003; p < 0.01). Postmenopausal obesity significantly increased breast tumor weight over the control (4.62±0.63 vs. 1.98±0.27 g; p < 0.01) and IMD (173±3.7 vs. 139±4.3 IM#/mm^2; p < 0.01). Tumor VEGF levels were higher in OVX/HF mice, compared to OVX/LF group (73.3±3.8 vs. 49.5±4.3 pg/mg protein; p < 0.01). Plasma VEGF levels (69±7.1 vs. 48±3.5 pg/ml) and visceral fat VEGF levels (424.4±39.5 vs. 208.5±22.4 pg/mg protein) were significantly increased in OVX/HF mice, compared to OVX/LF group, respectively (n=6; p < 0.01). Interestingly, adipose tissue primary culture showed that subcutaneous fat released more VEGF, compared to visceral fat (6.77±1.14 vs. 0.94±0.16 pg/mg tissue; n=6; p < 0.01). These findings support the hypothesis that postmenopausal obesity promotes tumor angiogenesis and breast cancer progression, possibly through increased adipose tissue mass and adipokines such as VEGF that could systemically and locally affect breast cancer progression.     

Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats.

PURPOSE: Exemestane (EXE) and letrozole (LET) are third-generation aromatase inhibitors currently prescribed for postmenopausal hormone-dependent breast cancer. The impact on end organs of estrogen depletion in menopausal women is of significant clinical importance. We studied the effects of EXE, its principal metabolite, 17-hydroexemestane (17-H-EXE), and LET on bone and lipid metabolism in ovariectomized (OVX) rats. EXPERIMENTAL DESIGN: OVX rats were treated by weekly intramuscular injection for 16 weeks with 20, 50, and 100 mg/kg EXE, 20 mg/kg 17-H-EXE, and daily oral gavage of 1 mg/kg LET. At the end of the treatment period, bone mineral density (BMD), the bone resorption marker serum pyridinoline, the bone formation marker serum osteocalcin, bone mechanical properties, histomorphometry, and serum lipid concentrations were determined. RESULTS: Lumbar vertebral and femoral BMD, bending strength of the femur, compressive strength of the fifth lumbar vertebra, and trabecular bone volume were significantly higher in OVX animals given EXE and 17-H-EXE than in OVX controls. EXE and 17-H-EXE significantly reduced an ovariectomy-induced increase in serum pyridinoline and serum osteocalcin. EXE and 17-H-EXE given to OVX rats caused significant reductions of serum cholesterol and low-density lipoprotein cholesterol. In contrast, OVX rats treated with LET had BMD, bone biomarkers, mechanical failure properties, and lipid levels similar to those of OVX controls. CONCLUSIONS: EXE and 17-H-EXE significantly prevent bone loss, enhance bone mechanical strength, and lower serum cholesterol and low-density lipoprotein levels in OVX rats. These protective effects on end-organ function are not seen with the nonsteroidal inhibitor LET.     

Effects of tamoxifen on spinal bone density in women with breast cancer

Bone densitometry (L2-L4) was performed on 10 postmenopausal women with breast cancer after 0, 6, and 12 months of tamoxifen treatment; the results were compared with data from 10 normal controls. The patients and controls differed significantly at 6 (P less than .05) and 12 (P less than .003) months. The tamoxifen group showed a nonsignificant mean gain in bone mineral density after 6 and 12 months of treatment (+0.024 +/- 0.014 and +0.022 +/- 0.018 g/cm2, respectively), whereas the controls showed a nonsignificant mean loss of bone mass at 6 months (-0.012 +/- 0.018 g/cm2) and a statistically significant loss of bone density after 12 months (-0.024 +/- 0.01 g/cm2). These preliminary data suggest that tamoxifen use is associated with preservation of bone mass during the first year of treatment.     

Combination of early bisphosphonate administration and irradiation leads to improved remineralization and restabilization of osteolytic bone metastases in an animal tumor model

BACKGROUND: The goal of the current study was to analyze the combined effect of bisphosphonates (BPs) and irradiation on remineralization and restabilization of osteolytic bone metastases in an animal tumor model. METHODS: Bone metastases were induced in male Wistar rats via intraosseous injection of the Walker carcinosarcoma 256B cell line into both proximal tibia metaphyses on Day 1 of the study. Three treatment groups were analyzed. All animals received a single radiation dose of 17 grays (in the form of 6-megaelectron-volt electrons) on Day 7 and were sacrificed on Day 49. Group 1 (the control group) was treated with irradiation only. Groups 2 and 3 received additional BPs (clodronate; daily intraperitoneal injection dose, 20 mg/kg per day). In Group 2, BPs were given before irradiation, on Days 3-6; this schedule later was referred to as early BP treatment. In Group 3, BPs were administered simultaneously with irradiation, on Days 7-10; this schedule later was referred to as simultaneous BP treatment. The endpoints of the study were bone density and microstructural parameters of bone on Day 49. Bone density was measured using X-ray absorption. Microstructural parameters of bone were assessed using histomorphometry. A total of thirty tibiae were analyzed in each group. RESULTS: After irradiation, bone density was significantly higher among animals in the early BP treatment group compared with those in the control group and those in the simultaneous BP treatment group (P = 0.001). Histomorphometric analysis of bone showed significantly better-preserved (P < 0.001) microstructural parameters (bone area, trabecular number, and trabecular separation) in the early BP treatment group compared with the control and simultaneous BP treatment groups. CONCLUSIONS: Early BP administration in combination with irradiation led to improved remineralization and restabilization of osteolytic bone metastases in an animal tumor model.     

The surgical management of the cavity and bone defects in enchondroma cases: A prospective randomized trial

BackgroundWe compared the curettage/bone grafting and the curettage/bone graft substitutes surgical techniques in their relation to functional outcomes, oncologic outcome (recurrence, malignant transformation), the rate of postsurgical complications, durations of surgery and of postsurgical immobilization for hand-localized cases of solitary and multiple enchondromas.MethodsThe current prospective randomized trial analyzed 200 adult patients (2012–2017) with enchondroma who underwent surgical intervention. The cases were randomly divided into Group 1 (n = 100; F 56, M 44) for surgeries with curettage and autogenous bone grafting, and Group 2 (n = 100; F 55, M 45) for surgeries with curettage and bone graft substitutes. The placebo control Group 3 consisted of cases operated by curettage only (n = 56; F 31, M 25). The follow-up period was set at 30 months.ResultsThe duration of surgery was 51 ± 4 min in Group 1 and 27 ± 1 min in Group 2 (p = 0.008). In Group 1, the rate of recurrence was 6% against 1% in Group 2 (p = 0.005). No other statistically significant differences in postsurgical outcomes between three involved groups were noted.ConclusionIn cases of enchondroma of the hand, postsurgical functional outcomes, the rate of postsurgical complications, the duration of immobilization, and the time to complete recovery are not influenced by the type of chosen grafting material. The implementation of HAp-collagen bone substitutes in granules instead of autogenous bone grafting reduces the duration of surgery. The implementation of autogenous bone grafting may increase the rate of tumor recurrence.     

塞莱西布对甲基硝基亚硝基胍诱导大鼠胃癌的化学预防作用

目的：探讨选择性环氧合酶-2（COX-2）抑制剂塞莱西布对N-甲基-N′-硝基-M亚硝基胍（MNNG）诱发大鼠胃癌的化学预防作用。方法：将120只雄性Wistar大鼠分成5组分别予以不同饮食及药物：胃癌模型组（M组,给予MNNG和高盐饮食）、塞莱西布早期干预组（MCE组）和晚期干预组（MCL组）、塞莱西布对照组（C组）和正常对照组（N组,纯净水）。喂养35周后观察各组大鼠的胃黏膜病变及胃癌形成情况。结果：111（92．5％）只大鼠完成实验。MCE组和MCL组大鼠胃癌发生率分别为4．3％和22．7％,均显著低于M组（71．4％,P〈0．001和〈0．010）;N组和C组均无胃癌发生。MCE组大鼠胃黏膜萎缩、肠化生和异型增生的发生率显著低于M组,P〈0．01;MCL组大鼠胃黏膜异型增生发生率亦显著低于M组,P〈0．05,但其萎缩和肠化生的发生率与M组之间无统计学意义。MCE组和MCL组大鼠胃黏膜COX-2蛋白表达的阳性率分别为26．1％和45．5％,亦显著低于M组（85．7％,P〈0．001和P〈O．01）。结论：选择性COX-2抑制剂塞莱西布能有效抑制MNNG诱导的大鼠胃癌及癌前病变的发生,这为C0X-2抑制剂对人类胃癌进行化学预防和治疗提供了实验证据。