阿霉素-磷酸钙骨水泥缓释体系的制备及体外药物释放试验

目的 以磷酸钙骨水泥(CPC)为载体，制备阿霉素—磷酸钙骨水泥药物缓释体系，观察其体外药物释放情况。方法 将阿霉素(ADM)包埋在磷酸钙骨水泥中，固化后的骨水泥进行体外药物溶出试验，用荧光光谱法研究药物在37℃模拟体液中的释放情况。结果 ADM可从载药磷酸钙骨水泥中缓慢释放，周期在1个月以上，药物的释放速度和浓度与CPC的药物包埋量有关，药物释放基本符合Higuchi等所建立的模型。结论 以CPC为载体，对ADM进行适当的包埋，可制备稳定的药物缓释体系，阿霉素—磷酸钙骨水泥缓释体系具备有修复骨缺损和药物治疗的双重功能。     

几丁糖顺铂缓释药膜的制备及体外抑制人胃腺癌SGC--7901细胞生长的研究

目的观察几丁糖-顺铂缓释药膜体外缓释性和对人胃腺癌SGC-7901细胞生长的抑制作用。方法将几丁糖与顺铂混合,加入交联剂戊二醛,真空干燥,制成几丁糖-顺铂缓释药膜,检测药膜的自然降解性、药膜顺铂含量和药物包封率,同时观察药膜体外缓释顺铂及其对胃癌细胞生长的抑制作用。结果几丁糖-顺铂缓释药膜在含溶菌酶的生理盐水中于8天后开始自然降解,60天后降解率达83.33%;药膜载药率为(7.30±0.20)%,药物包封率为(51.78±2.10)%;药膜体外释放顺铂量于第1天达75.40μg/ml,第2天释放量明显降低,为21.35μg/ml,以后呈较低水平缓慢释放,第7天达3.94μg/ml,并且,其浸出液体外抑制胃癌细胞生长的抑制率第1天为84.24%,以后渐降低,第7天达29.81%。结论几丁糖-顺铂缓释药膜在体外可较好地缓释顺铂,对人胃腺癌SGC--7901细胞的生长有较持久地抑制作用。     

聚甲基丙烯酸甲酯骨水泥作为抗肿瘤药物缓释载体的实验研究

目的:探讨聚甲基丙烯酸甲酯(PMMA)骨水泥加入抗肿瘤药物后物理和力学性能的变化,以及抗肿瘤药物在体外释放的情况.方法:在40 g骨水泥中分别加入50 mg多柔比星、20 mg唑来膦酸.并设立单纯的骨水泥组作为对照.在无菌条件下将骨水泥按照ISO5833:2002<外科植入物--丙烯酸类树脂骨水泥>的标准制成各种试件,测定其抗压强度、抗弯模量和抗弯强度.同时将试件进行浸泡洗提.检测其药物的释放情况.结果:与对照组相比,骨水泥的物理和力学性能没有明显的改变,对照组和实验组骨水泥的抗压强度、抗弯模量、抗弯强度,差异无统计学意义.P>0.05.两种药物均能从骨水泥中缓慢的释放出来,药物的释放规律及释放量基本相同.多柔比星释放总量占药物初始剂量的0.83%,唑来膦酸释放总量占药物初始剂量的0.66%.结论:抗肿瘤药物能有效地从骨水泥中缓慢的释放,40 g骨水泥中加入<1 g的药物不会影响骨水泥的物理和力学性能,PMMA骨水泥适合作为抗肿瘤药物的缓释载体.     

鹿瓜多肽促进磷酸钙人工骨对兔下颌骨缺损的修复作用

目的研究注射鹿瓜多肽注射液结合自固化磷酸钙人工骨(calcium phosphate cement,CPC)对兔下颌骨缺损修复作用的影响。方法 36只新西兰大白兔制成下颌骨双侧10 mm×4 mm×4 mm缺损的模型,实验组(18只)植入CPC,并每日给予0.2 ml/kg鹿瓜多肽注射液肌注;对照组(18只)植入自固化人工骨,每日给予等量生理盐水肌注。在分别于2、4、6、8 w处死,进行锥形束CT(cone beam CT,CBCT)及免疫组织化学观察。结果 CBCT观察:2、4、6、8 w时实验组骨缺损处的愈合情况优于对照组骨缺损处骨愈合的情况,第8 w时,实验组骨缺损处边缘连续,骨痂形成且密度基本与正常骨组织密度一致;免疫组织化学观察:在2、4、6 w时实验组的BMP-2的表达量早且高于对照组,在第6 w时实验组的BMP-2的表达量达到最高峰,8 w时,实验组BMP-2染色细胞阳性数目低于对照组。结论鹿瓜多肽注射液对植入CPC材料的骨缺损愈合具有良好的促进作用。     

骨巨细胞瘤的体外药物敏感试验

 骨巨细胞瘤是一种半恶性的肿瘤，术后复发率较高。作者取经病理证实的骨巨细胞瘤标本（共7例）进行体外培养，并用MTT法进行原代细胞的化疗药物敏感试验及梯度浓度的化疗药物的敏感试验，结果显示，在常规剂量下（临床一次用量的1／250）骨巨细胞瘤对阿霉素及顺氨氯铂中度敏感，梯度试验表明，阿霉素、顺氨氯铂及甲氨蝶吟的最低有效抑制浓度分别为0．4ug／ml、2ug／ml和3us／ml，因此，骨巨细胞瘤可以应用阿霉素、顺氨氯铂等进行治疗以降低术后复发率，但由于有效浓度较高，不适合常规的静脉及局部给药，而仅适用于良好缓释载体与敏感化疗药物制成的缓释制剂的局部应用。     

顺铂纳米脂质体的小鼠体内药代动力学研究

背景与目的:顺铂是临床常见的具有放疗增敏作用的抗肿瘤药物,但由于其进入体内迅速与血浆蛋白结合而限制了放疗增敏作用的发挥,顺铂的缓释制剂有望延长药物的作用时间,增加疗效,并降低毒性,因此本研究旨在探索长循环纳米脂质体包裹的顺铂在小鼠体内的药物动力学过程。方法:选用C57BL/6N近交系Lewis肺癌荷瘤小鼠80只(肿瘤生长5～7d),分成两组,普通顺铂组(CDDP)和顺铂脂质体组(LDDP),尾静脉分别注射顺铂注射液和顺铂长循环纳米脂质体,剂量均为6mg/kg,于注射后不同的时间取血并处死动物,取肿瘤、肾、肝和肺组织,每个时间点各5只小鼠。采用高效液相色谱法(HPLC)测定游离铂的含量。药动学软件3P97进行数据分析。结果:CDDP组小鼠在注射后游离铂立即达到最高血药浓度3.24μg/ml,并迅速降低,2h后在血液中已经无法检测出游离铂。LDDP组小鼠注射后1h,血浆游离铂达峰浓度13.79μg/ml,是CDDP组峰浓度的4倍多。72h后血药浓度为1.04μg/ml,血中顺铂浓度呈明显的两相性变化过程,初始相顺铂浓度快速下降,半衰期为1.27h,其后第二相顺铂浓度缓慢下降,半衰期为19.47h。结论:顺铂纳米脂质体新配方,使游离铂的血药浓度长时间维持在相对较高的水平。初步达到了长循环,缓释的要求。     

大剂量顺铂股动脉灌注联合血液透析动物模型的试验研究

目的 研究大剂量顺铂动脉灌注联合血液透析在提高肢体肿瘤化疗药物剂量强度，减少药物在正常组织器官分布方面的作用。方法 体外实验中，将顺铂加入血浆，经血液透析，测定透析前后血浆中及透析液中的铂浓度；体内实验中16只犬随机分为2mg／kg对照(A组)和实验组(B组)，及4mg／kg对照(C组)和实验组(D组)。分别经右股动脉顺铂灌注，实验组右殷静脉插管接血液透析机。采用原子吸收法测定不同时间血液透析机动、静脉端及外周血样、各脏器组织中的铂浓度。结果 在各剂量组中，实验组外周血药浓度—时间曲线下面积(AUC)及外周器官中铂浓度均低于对照组，而灌注化疗肢体局部组织中铂浓度无显差异。D组中灌注化疗肢体局部组织中铂浓度高于B组，而AUC值及外周器官中铂浓度则无显性差异。结论 与普通顺铂股动脉灌注相比，联合血液透斫治疗可以明显降低实验动物外周血药浓度和组织器官药物浓度，在不增加外周药物分布的前提下，有效提高肢体局部用药剂量。     

成骨诱导自体脂肪源性干细胞用于修复兔颅骨缺损

目的探讨脂肪源性干细胞作为骨组织工程的种子细胞在修复骨缺损中的应用前景。方法提取兔脂肪源性干细胞,成骨诱导,将成骨诱导前后的脂肪源性干细胞种植到自制松质骨支架上,将细胞-支架复合物和单纯支架材料,分别移植至兔颅骨缺损部位。术后14周,处死取材,Micro-CT扫描。结果与未诱导的脂肪源性干细胞复合支架、单纯支架以及空白处理对比,成骨诱导后的脂肪源性干细胞复合支架成骨量显著增高,差异具有统计学意义。结论脂肪源性千细胞可作为骨组织工程的种子细胞,其成骨诱导后与自制松质骨复合植入体内,能显著促进骨缺损的修复。     

用于肺癌治疗的带缓释化疗药栓塞装置在动物体内的特性研究

目的研究用于肺癌治疗的带缓释化疗药栓塞装置,在动物体内的栓塞、药物释放特性及对羊肺组织的影响,评价其应用的可行性.方法用镍-钛记忆合金支架、Ivalon泡沫海棉及顺铂制备栓塞装置.采用萨能妈山羊12只,随机分为带药栓塞组和灌注组(对照组),每组6只.带药栓塞组在介入下于右下肺动脉置入带缓释化疗药(顺铂2 mg/kg)的栓塞装置,并造影,然后开胸置右下肺静脉抽血管,对照组在开胸下置右下肺静脉抽血管后行右下肺动脉灌注顺铂(2 mg/kg),两组术后均定时抽血测右下肺静脉及外周血顺铂浓度、外周血气和血常规,3天后处死动物行病理解剖.结果带药栓塞组栓塞即刻造影肺动脉均未完全阻塞,3天后造影及处死后解剖均见已完全阻塞,栓塞后动物无明显并发症,带药栓塞组1、2、8 h测得的肺静脉血药浓度均高于灌注组(P＜0.05),其曲线下面积也高于肺脉灌注组(P＜0.05),而外周血顺铂浓度大多均未高于肺动脉灌注组.结论此装置可以经介入的方法置入肺动脉内,栓塞后对动物羊肺组织的影响小,有利于提高肺组织局部药物的浓度,同时能降低外周血循环中的药物浓度.     

组织内泵入式化疗给药系统初探

目的:探讨通过局部组织吸收化疗药物的靶向控释给药系统的安全性与可行性。方法:自制植入式化疗给药泵装置,并植入实验兔体内,将5-Fu持续、直接释放于兔子的肌肉和皮下组织内,设立自身两侧对照,不同时间取材,病理检验给药与非给药后的组织改变,统计评价两者之间的差异。结果:给药与非给药后的组织病理改变差异无统计学意义。结论:组织内低浓度缓慢泵入5-Fu,依靠局部组织吸收,进行化疗这一控释给药靶向系统是安全可行的。     

洛铂联合多西他赛行肿瘤细胞减灭术加腹腔热灌注化疗治疗腹膜癌的临床观察

目的 分析洛铂联合多西他赛行肿瘤细胞减灭术（cytoreductive surgery, CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy, HIPEC）治疗腹膜癌（peritoneal carcinoma, PC）的围手术期安全性及疗效。 方法 PC患者行CRS+HIPEC治疗,药物为洛铂50 mg/m2、多西他赛60 mg/m²,加入12 000 ml 0.9%氯化钠溶液加热至（43±0.5）℃持续灌注60 min。记录术后6天体温和心率变化、围手术期不良事件、血常规及血生化指标、术后患者恢复情况及生存结果。结果 90例PC患者行95次CRS+HIPEC,手术时间180~450 min (中位数485 min）;术后6天最高体温、心率分别为36.4℃~38.6℃（中位数37.5℃）、76~124 bpm（中位数100 bpm）,严重不良事件16例,包括围手术期死亡2例。中位生存期20.8月（95%CI: 13.1~25.8月）,1、3、5年生存率分别为75.6%、45.6%、43.3%。 结论 洛铂联合多西他赛进行CRS+HIPEC治疗PC安全性可接受,有助于延长患者生存期。     

Endoscopic Endonasal Dacryocystorhinostomy: Best Surgical Management for DCR

EEDCR is a highly rewarding Endoscopic procedure for management of dacryocystitis when epiphora does not respond to medications or repeated syringing of nasolacrimal duct. It is a simple, less time consuming, safe but skilful, highly satisfying surgery both for the patients as well as the surgeons. There is very big advantage of EEDCR, it is close 100% successful procedure, even if there is recurrence of epiphora it is again correctable fully with no residual affects. EEDCR is far more superior to External DCR/Laser DCR and there are definite reasons for it. A total number of 578 cases have been operated by me from April 1, 2005 to March 31, 2011, only very few reoccurrences were there and they were corrected easily so much so that it can be said that it is a close 100% successful procedure and best surgical management of DACRYOCYSTITIS up to date. The successful outcome was defined as symptomatic relief from epiphora and dacryocystitis and a patent nasolacrimal duct upon syringing at the end of procedure and on follow up of patient.     

参麦注射液对阿霉素所致大鼠心肌损伤保护作用的实验研究

目的　观察参麦注射液 (SMI)对阿霉素 (ADM )诱导大鼠心肌损伤的保护作用和抗氧化作用。方法　选用ADM诱导大鼠心肌损伤模型。SD大鼠 60只 ,随机分为 3个组 ,每组 2 0只 ,分别为正常组、治疗组、对照组。正常组 :实验第 1～ 9天注射生理盐水 ,每天 3ml/kg ,1次 /天。治疗组 :实验第 1～ 9天注射参麦注射液 ,每天 3ml/kg ,1次 /天 ,第 4天注射阿霉素 ,隔天 1次 ,连用 3次 ,用生理盐水配置成 1mg/ml,每次 3mg/kg。对照组实验 1～ 9天注射生理盐水 ,每天 3ml/kg ,1次 /天。第 4天注射阿霉素 ,以后隔天 1次 ,连用 3次 ,用生理盐水配置成 1mg/ml,每次 3mg/kg。到期测定血丙二醛 (MDA )含量和超氧化物歧化酶(SOD )活性 ,并进行心肌病理检查。结果　对照组MDA水平明显高于治疗组 ,对照组SOD水平则显著低于治疗组 ,即加用SMI可提高SOD活性 ,降低MDA含量。SMI能明显减轻大鼠心肌损伤 ,对照组与治疗组比较 ,治疗组心肌损伤明显减轻 ,治疗组与正常组比较无显著性差异。参麦注射液有抗氧化作用 ,与对照组比较 ,血SOD水平升高 ,MDA水平降低 ,心肌病理计分下降。结论参麦注射液有抗氧化作用和对阿霉素所引起的心脏毒性具有保护作用 ,为临床寻找有效的阿霉素所致心肌损伤保护药物提供良好的客观依据 ,值得临床推广应用     

Denosumab in patients with cancer and skeletal metastases: A systematic review and meta-analysis

Background

We conducted a systematic review of the literature to determine the efficacy and safety of denosumab in reducing skeletal-related events (SRE) in patients with bone metastases.

Methods

A literature search using MEDLINE, EMBASE, Web of Science and The Cochrane Collaboration Library identified relevant controlled clinical trials up-to-March 14, 2012. Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. The primary outcomes of interest were SRE, time to first on-study SRE, and overall survival. Secondary outcomes included pain, quality of life, bone turnover markers (BTM), and adverse events.

Results

Six controlled trials including 6142 patients were analyzed. Compared to zoledronic acid, denosumab had lower incidence of SRE with a risk ratio (RR) of 0.84 (95% confidence intervals (CI) 0.80–0.88), delayed the onset of first on-study SRE (RR 0.83; 95% CI 0.75–0.90) and time to worsening of pain (RR 0.84; 95% CI 0.77–0.91). No difference was observed in overall survival with pooled hazard ratio of 0.98 (95% CI 0.90–1.0). For total adverse events, denosumab was similar to zoledronic acid (RR 0.97; 95% CI 0.89–1.0). No significant differences were observed in the frequency of osteonecrosis of the jaw (RR 1.4; 95% CI 0.92–2.1). Patients on denosumab had a greater risk of developing hypocalcemia (RR 1.9; 95% CI 1.6–2.3).

Conclusions

Denosumab was more effective than zoledronic acid in reducing the incidence of SRE, and delayed the time to SRE. No differences were found between denosumab and zoledronic acid in reducing overall mortality, or in the frequency of overall adverse events.     

体内诱导艾氏腹水瘤细胞的耐药性研究

肿瘤细胞耐药性的存在是临床化疗失败的主要原因之一。本实验在小鼠体内用阿霉素（ADR）诱导艾氏腹水瘤细胞（EHR）的耐药性，探讨细胞产生耐药性的机理。HPLC法测定细胞内药物浓度．结果表明耐药细胞─—EHR/ADR细胞内ADR积聚低于EHR细胞，而对ADR外排快于EHR细胞；异博定（VER）增加EHR／ADR细胞对ADR的摄取并阻滞其外排．而对EHR影响不大，揭示EHR／ADR细胞具有MDR特性。     

Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis

The aim of this study was to determine the efficacy of palliative oxygen for relief of dyspnoea in cancer patients. MEDLINE and EMBASE were searched for randomised controlled trials, comparing oxygen and medical air in cancer patients not qualifying for home oxygen therapy. Abstracts were reviewed and studies were selected using Cochrane methodology. The included studies provided oxygen at rest or during a 6-min walk. The primary outcome was dyspnoea. Standardised mean differences (SMDs) were used to combine scores. Five studies were identified; one was excluded from meta-analysis due to data presentation. Individual patient data were obtained from the authors of the three of the four remaining studies (one each from England, Australia, and the United States). A total of 134 patients were included in the meta-analysis. Oxygen failed to improve dyspnoea in mildly- or non-hypoxaemic cancer patients (SMD=-0.09, 95% confidence interval -0.22 to 0.04; P=0.16). Results were stable to a sensitivity analysis, excluding studies requiring the use of imputed quantities. In this small meta-analysis, oxygen did not provide symptomatic benefit for cancer patients with refractory dyspnoea, who would not normally qualify for home oxygen therapy. Further study of the use of oxygen in this population is warranted given its widespread use.     

邻近腋窝的上皮样血管内皮瘤1例报道

We described a case of a 71-year-old woman with an epithelioid hemangioendothelioma (EHE) in her left axilla,a rare location which hasn't been reported yet. The patient suffered from numbness, pain and decreased muscle strength of her left upper extremity. Sonography revealed a hypoechoic mass surrounded the axillary artery and brachial artery. No obvious capsule was demonstrated. CT showed a soft-tissue mass with some calcifications and peripheral ring-like en-hancement. The MRI indicated a mass with mainly intermediate signal intensity on Tl-weighted imagine and intermediate signal intensity on T2-weighted imagine. The diagnosis was confirmed by histopathologic examination after surgery. There are some correlations of these imaging features with its histopathologic characters.     

GF方案与TP方案一线治疗晚期非小细胞肺癌的临床对照研究

Objective  

The aim of the study was to evaluate the efficacies of initial gemcitabine plus cisplatin (GP) and paclitaxel plus cisplatin (TP) 1st-line chemotherapies for advanced non-small cell lung cancer (NSCLC) and observe their side effects.     

鼻咽癌患者放射性骨坏死引起的正电子显像假阳性结果1例及文献复习

目的:探讨鼻咽癌(NPC)患者放射性骨坏死(osteoradionecrosis,ORN)引起正电子假阳性结果的原因及避免因此引发诊断错误的方法。方法:回顾性分析1例放疗后的鼻咽癌患者,行鼻咽部MRI及正电子显像后,再行组织病理学检查,对三种结果进行分析、比较。结果:MRI及正电子显像均诊断患者颅底区域肿瘤复发,组织病理学结果则显示鼻咽部病灶为放射性骨坏死。因此正电子扫描结果为假阳性结果。结论:鼻咽癌患者放疗后所致的放射性骨坏死容易引起正电子显像假阳性结果并可能引发不必要的治疗,因此NPC患者的正电子图像,对于可能的局限性肿瘤复发诊断,应该非常慎重。     

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence

Background: Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. Case presentation: A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. Discussion: CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. Conclusion: In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.