放疗同步替莫唑胺化疗治疗恶性胶质瘤临床观察

目的研究术后放疗同步替莫唑胺(RT-TMZ)治疗恶性胶质瘤的近期疗效和不良反应。方法收集2008年11月-2009年5月在我院确诊的61例恶性胶质瘤术后患者,按照患者自愿选择的治疗方案分为RT-TMZ组和单纯放疗(RT)组。RT-TMZ组31例,行放疗(总剂量60Gy,共治疗6周)期间同时持续口服替莫唑胺(Temozolomide,TMZ)化疗(75mg/(m2·d),共42d),放疗结束后续行TMZ辅助化疗150-200mg/(m2·d),共4-6个周期;RT组30例,单纯放疗6周,总剂量60Gy。结果RT-TMZ组与RT组有效率(CR+PR)分别为79.3%(23/29)、53.3%(16/30),疾病控制率(CR+PR+SD)分别为89.7%(26/29)、83.3%(25/30),P<0.05。RT-TMZ组6个月无疾病进展生存率为71.0%(22/31),患者对治疗的耐受性良好;不良反应为恶心、呕吐和乏力,白细胞和血小板下降基本限于I-Ⅱ度。结论恶性胶质瘤术后放疗同步替莫唑胺治疗近期疗效良好,不良反应较轻,是切实可行的治疗方案。     

紫杉醇卡铂化疗联合放射治疗局部晚期非小细胞肺癌临床观察

目的 :观察紫杉醇卡铂化疗联合放射治疗局部晚期非小细胞肺癌 (NSCL C)的近期疗效及毒副反应。方法 :3 2例局部晚期NSCLC患者 ,采用紫杉醇加卡铂联合化疗 (紫杉醇 13 5 mg/m2 ,静滴 ,第 1天 ;卡铂 3 0 0 mg/m2 ,静滴 ,第 2天 ,每 2 1天为 1周期 ,共 2～ 3周期 ) ,并与放射治疗 (常规分割 ,DT62～ 68Gy/3 1～ 3 4次 )交替进行 (夹心疗法 )。结果 :全组 CR2例 ,PR16例 ,总有效率 (CR PR) 5 6.3 % ,无严重毒副反应。平均生存期 14 .5月。结论 :紫杉醇卡铂化疗联合放射治疗局部晚期 NSCLC能提高近期疗效 ,远处转移有降低趋势 ,且毒副作用可耐受 ,值得临床进一步观察研究     

钴60多野适形放射治疗晚期非小细胞肺癌临床研究

目的：探讨立体定向放射治疗晚期非小细胞肺癌的近期疗效和放疗副反应。方法：采用钴60多野适形放射治疗系统（-刀）治疗58例（82个病灶）晚期非小细胞肺癌患者。50%等剂量线覆盖PTV,95%等剂量线包绕100%GTV,照射剂量以50%等剂量线作为处方剂量,单次剂量3Gy至5Gy,1次/天,5次/周,共照射8次至14次,总剂量30Gy至50Gy。结果：55例78个病灶根据CT复查肿瘤退缩情况确定CR为21.8%,PR为69.2%,总有效率为91.0%;临床获益率为76.5%;1年以上生存率为38.5%。结论：SRT使肿瘤局部受到准确照射,周围正常组织损伤小,近期疗效满意。     

低剂量伽玛刀照射实验性癫痫老龄大鼠海马神经元超微结构观察

目的:观察低剂量伽玛刀照射实验性老龄癫痫大鼠海马神经元超微结构的变化。方法:采用青霉素定位浸润建立老龄大鼠癫痫动物模型,将57只老龄大鼠分为对照组、癫痫组和癫痫后伽玛刀照射组。照射周边剂量12Gy,等剂量曲线为50%,0.5 h～60 d后取靶区海马制备电镜样品,透射电镜观察。结果:对照组海马神经元的超微结构正常;癫痫大鼠可见神经元细胞器明显空化,部分神经元凋亡;伽玛刀照射组早期与癫痫模型组基本一致,中期和晚期部分结构得以恢复,线粒体修复较为明显。结论:老龄癫痫大鼠经低剂量伽玛刀照射,中、晚期海马神经元的超微结构改变得以修复,可为临床治疗老龄癫痫提供形态学依据。     

伊班膦酸钠分别联合放疗和化疗治疗骨转移癌的临床评价

目的:比较伊班膦酸钠分别联合放疗和化疗治疗骨转移癌的疗效和毒副反应。方法:90例患者随机分为两组,伊班膦酸钠 放疗组(联合放疗组)45例,伊班膦酸钠 化疗组(联合化疗组)45例。采用伊班膦酸钠6mg加入生理盐水500mL静滴4h以上,每4周重复,每例病人应用4~6次。放疗方法骨转移灶剂量为30~40Gy/2~3周,化疗根据原发肿瘤类型选择相应方案。结果:联合放疗组和联合化疗组1、3、6月疼痛缓解率、骨转移灶有效率分别为91.1%、86.7%、82.1%;84,4%、82.2%、82.9%和40.0%、48.9%、59.0%;37.8%、44.4%、61.0%。两组比较P>0.05,差异无统计学意义。结论:伊班膦酸钠分别联合放疗和化疗治疗骨转移癌的疗效相似,毒副作用可以耐受。     

垂体腺瘤放射治疗的长期疗效分析(附96例报道)

目的:评价垂体腺瘤患者接受常规放射治疗后的长期疗效和毒性;探讨影响疗效的因素.方法:从1988年1月到1998年1月共收治96例垂体腺瘤患者行常规放射冶疗.44例分泌激素,52例不分泌激素,73例为术后放射冶疗,23例为复发放射治疗;50例采用钴60γ线照射,46例采用6MV X线照射;平均照射剂量45Gy(43.2Gy至50.0Gy);全组中位随访时间6.5年(0.8年至20.0年),存活患者中位随访时间6.1年(2.0年至20.0年).结果:全组尤功能性腺瘤和功能性腺瘤10年局控率分别为96.2%和72.7%(P=0.001),10年疾病专项生存率(CSS)分别为94.2%和88.6%(P=0.319),10年总生存率分别为69.2%和77.3%(P=0.395).激索分泌显著降低局控率(P=0.012);蝶窦受累降低10年CSS(P=0.039),CSS与激素分泌、手术范围、术后或复发放疗无明显相关.35例患者出现垂体功能减退:视力丧失和继发性脑胶质瘤各2例.结论:适当剂量的放射治疗能使切除不伞或术后复发的垂体腺瘤患者获得满意的长期控制率,严重并发症相对较少;激索分泌、蝶窦受累显著影响疗效.     

肺癌患者化疗的治疗报告

为了减轻病员住院经济负担、探讨肺癌在门诊化疗的可行性及疗效 ,我院专家门诊从 1998～ 1999年对 2 3例中晚期肺癌不能手术治疗患者 (其中非小细胞癌 2 0例、小细胞肺癌 3例均经纤维支气管镜活检证实 )。根据细胞类型制定不同化疗方案并配合应用沙星力康辅助化疗 ,取得较为满意疗效 ,全部病例均取得部分缓解 ,未发生明显化疗毒副反应 ,如期完成 1～ 3个疗程化疗 ,现将我们点滴体会报告如下。1　化疗方案1 1　非小细胞性肺癌采用治疗方案环磷酰胺 40 0ｍｇ/Ｍ2 生理盐水 10 0ｍｌ静滴。阿霉素40ｍｇ/Ｍ2 生理盐水 10 0ｍｌ静滴。顺铂 40ｍ…     

LANSCLC预后因素的临床研究

目的：观察74例局部晚期非小细胞肺癌（locally advanced non-small cell lung cancer,LANSCLC）患者综合治疗后的1年、2年和3年总生存率,总结临床因素对患者疗效及预后的影响。方法：收集74例在重庆医科大学附属第一医院肿瘤科施行化疗和放射治疗的LANSCLC患者病史及随访资料,计算生存率,筛选预后不良因素。结果：全组治疗后1年,2年,3年总生存率（0S）为79.7%,2年总生存率为49.0%,3年总生存率为18.8%,中位生存时间为24个月。单因素和多因素分析显示放化疗方式及手术与否各组间患者的生存率曲线分布差异有统计学意义（p〈0.05）;而不同化疗方案,化疗周期数各组间患者的生存率曲线分布差异无统计学意义（p〉0.05）。结论：放化疗结合方式,手术与否对LANSCLC患者预后有影响。     

氟达拉滨联合利妥昔单抗治疗高龄慢性淋巴细胞白血病

目的考察氟达拉滨联合治疗高龄慢性淋巴细胞白血病患者的有效性和安全性。方法应用氟达拉滨联合利妥昔单抗方案治疗11例患者,根据患者情况分次给药,25~30mg/m2隔日或每周1~2次静脉注射,或口服剂型10mg~20mg/d连续用药,观察患者应用氟达拉滨过程中及其后的不良反应及疗效。结果全组11例患者CR+PR为10例,其中CR6例,PR4例,NR1例。不良反应主要为粒细胞及血小板减少等骨髓抑制,未出现严重感染,无化疗相关死亡。结论氟达拉滨联合利妥昔单抗治疗高龄慢性淋巴细胞白血病具有较高的安全性和有效性。     

光动力学疗法与膀胱内灌注化疗治疗膀胱癌远期疗效比较

选病理分期T1,T2的膀胱癌病人60例,随机分成3组进行治疗.试验组A[经尿道膀胱肿瘤切除(TURBT)+光动力学治疗(PDT)]17例和试验组B(TURBT+PDT+膀胱内灌注化疗)15例,常规治疗对照组(TURBT+膀胱内灌注化疗)28例.试验组A和B(PDT组)在口服光敏剂CDHS801(200 mg/50 kg)24 h后进行PDT,能量密度为50 J/cm2.72 h后行TURBT手术,治疗期间不避光.试验组患者分别进行膀胱内灌注化疗或者不进行内膀胱灌注化疗,对照组按照常规治疗方式进行TURBT手术和膀胱内灌注化疗.研究结果表明,试验组A的患者生活质量显著优于对照组(P＜0.05);试验组A和B患者的肿瘤复发率也显著低于对照组(P＜0.05);而5年生存率和肿瘤进展率两项指标试验组与对照组相比无统计学差异.所以,在治疗T1,T2期膀胱癌时,作为常规手术切除的辅助治疗,术前进行PDT治疗与术后行膀胱内灌注化疗相比,可能存在肿瘤复发率低、患者生存率以及患者生活质量有所提高的优势.     

Dual-row needle arrays under an electromagnetic thermotherapy system for bloodless liver resection surgery

Electromagnetic thermotherapy has been extensively investigated recently and may become a new surgical modality for a variety of medical applications. It applies a high-frequency alternating magnetic field to heat up magnetic materials inserted within the human body to generate tissue coagulation or cell apoptosis. Using a new procedure with dual-row needle arrays under an electromagnetic thermotherapy system with a feedback temperature control system, this study demonstrates bloodless porcine liver resection, which is challenging using existing methods. In vitro experiments showed that hollowed, stainless-steel needles could be heated up to more than 300 °C within 30 s when centered under the induction coils of the electromagnetic thermotherapy system. In order to generate a wide ablation zone and to prevent the dual-row needle arrays from sticking to the tissue after heating, a constant temperature of 120 °C was applied using a specific treatment protocol. The temperature distribution in the porcine livers was also measured to explore the effective coagulation area. Liver resection was then performed in Lan-Yu pigs. Experimental results showed that seven pigs underwent liver resection without bleeding during surgery and no complications afterward. The dual-row needle arrays combined with the electromagnetic thermotherapy system are thus shown to be promising for bloodless tissue resection.     

Effect of silicon thickness on the degradation mechanisms of sequential laterally solidified polycrystalline silicon TFTs during hot-carrier stress

We have investigated bias stress-induced aging effects in polycrystalline silicon thin-film transistors (poly-Si TFTs), as a function of the active layer thickness. Two aging mechanisms were identified: hot-carrier injection in the gate insulator and deep-state generation in the active "body." Hot-carrier injection was found dominant in devices having very thin (30 nm) or thick (100 nm) active layers. Deep-state generation dominated in devices having intermediate active layer thickness (50 nm). The fully depleted aspect of ultrathin active-layer devices, as well as their relative immunity to substantial degradation under bias stress, favor the implementation of thin active layer for the fabrication of high-performance and high-reliability poly-Si TFTs.     

用于激光热疗的激光抽运高掺杂光纤光热头研究

利用晶体光纤中高掺杂离子的非辐射跃迁机制,研制成功一种可用于激光热疗的高掺杂光纤光热转换头。在一个809nm半导体激光器抽运下,光热头在空气和蛋清样品中分别产生最高达465℃(抽运功率为1124mW)和98℃(抽运功率为933mW)的温度,已足够用于激光热疗。同时,光热头在温度稳定性、热响应时间、生物相容性、抗热冲击强度和化学稳定性等方面均能满足要求。     

A Chemoimmunotherapy Nanogel Enables Efficient Delivery of Interleukin-2 and Induction of Immunogenic Cell Death for Effective Cancer Therapy

Interleukin-2 (IL-2) is one of the first FDA-approved immunotherapeutics, but its use is limited by toxicity and low efficacy. In addition, all immunotherapies are limited by the immunosuppressive and desmoplastic microenvironment of “immunologically cold” tumors, such as pancreatic ductal adenocarcinoma (PDAC) or hepatocellular carcinoma (HCC) with advanced liver fibrosis. Here, a new chemoimmunotherapy nanogel (IL2-Pt@Nanogel) for dual delivery of IL-2 and the type II immunogenic cell death inducer Pt-NHC that reduces the immunosuppressive phenotype of tumor-associated macrophages and diminishes regulatory T cell infiltration by inducing the production of type I interferon (IFN) by cancer cells is reported. Combining the angiotensin II receptor blocker losartan with IL2-Pt@Nanogel treatment reduces desmoplasia and reprogrammes the microenvironment of PDAC and HCC toward an immunostimulatory one. These effects result in potent anti-tumor efficacy in models of primary and metastatic PDAC and HCC with underlying liver fibrosis. This study presents a strategy for IL-2-based chemoimmunotherapy with the potential for clinical translation to treat solid tumors.     

Synergistic Sonodynamic/Chemotherapeutic Suppression of Hepatocellular Carcinoma by Targeted Biodegradable Mesoporous Nanosonosensitizers

Hepatocellular carcinoma (HCC) is one of the deadliest malignancies worldwide featured with the poor prognosis and high mortality in affected patients. Given its insensitivity to conventional systemic chemotherapy, the development of novel modalities for HCC management is highly urgent. Sonodynamic therapy (SDT) has gained considerable momentum in cancer therapy. Especially, through synergistic SDT/chemotherapy, SDT would enhance the chemotherapeutic process on inhibiting tumor growth, which holds great potential on combating HCC. In this work, we report on the design/fabrication of targeted biodegradable nanosonosensitizers based on hollow mesoporous organosilica nanoparticles (HMONs), followed by pore‐engineering including covalent anchoring of protoporphyrin (PpIX, HMONs‐PpIX) and conjugation of arginine‐glycine‐aspartic acid in order to specifically targeting HCC cells. Such nanosonosensitizers provide efficient loading and controllable stimuli‐responsive release of chemotherapeutic agents for HCC‐targeting chemotherapy, thus promoting an enhancing chemotherapeutic process via the unique sonotoxicity under ultrasound irradiation. The HMONs matrix with biologically active organic groups in the framework (disulfide bond) are endowed with intrinsic tumor microenvironment‐responsive biodegradability and improved biocompatibility/biosafety. In particular, a synergistic inhibition effect of drug‐loaded HMONs‐PpIX‐arginine‐glycine‐aspartic acid on HCC growth has been systematically demonstrated both in vitro and in vivo (84.7% inhibition rate), which brings insights and meets the versatile therapeutic requirements for HCC management.     

Quantification of the 3-D electromagnetic power absorption rate intissue during transurethral prostatic microwave thermotherapy using heattransfer model

Experiments were performed in a tissue microwave-equivalent phantom gel to quantitatively examine the volumetric heating produced by a microwave antenna with a peripheral cooling system for the transurethral prostatic thermotherapy. Based on previous research, expression for the specific absorption rate (SAR) of microwave energy in the gel was extended to three dimensions, which includes its dependence on radial, angular, and axial direction. A theoretical heat transfer model was developed to study the temperature distribution in the gel by introducing this proposed SAR expression. The parameters in this expression and the convection coefficient due to the chilled water running around the antenna were determined using a least-square residual fit of the theoretical temperature predictions to the experimentally measured steady-state temperature field within the gel. The analytical expression of the three-dimensional SAR distribution obtained in this study will help provide a better understanding of the microwave heating pattern in the prostatic tissue and, thus, to aid in designing improved applicators. It can also be used in the future as an accurate input to heat transfer models which predict temperature distributions during the transurethral microwave thermotherapy     

Flexible Induction Heater Based on the Polymeric Thin Film for Local Thermotherapy

Local delivery of physical energy, such as heat, is promising for the treatment of target lesions without the unintended distribution of heat to other normal tissue. However, the heating device must be equipped with an external power source or strong magnetic field to operate the device, and many of them are too large to be placed inside the body. In this regard, wireless, lightweight, flexible electronics can be used for the miniaturization of implantable devices. In this study, a flexible induction heating (IH) device is reported that integrates inkjet-printed wirings and flexible polymeric thin films, specifically Au nanoink-based wirings (thickness: 1.5 µm) and a biodegradable poly(D, L-lactic acid) (PDLLA) thin film (thickness: 5 µm). A unique method of transferring the inkjet-printed Au nanoink wiring onto the PDLLA thin film realizes the integration of the following technical features in one device: biocompatible packaging, a printed IH system, and body conformability. The resulting thin-film IH device is successfully placed on a hepatic lobe of a beagle dog, which allows for a local increase in temperature of 7 °C after 1-min power feeding without tissue inflammation. The thin-film IH device is expected to provide minimally invasive thermotherapy when combined with endoscopic surgery.     

Cuproptosis-Driven Enhancement of Thermotherapy by Sequentially Response Cu2-xSe via Copper Chemical Transition

Activation of cuproptosis pathway has been reported to hold great potential in the application of tumor treatment. But the efficacy of cuproptosis seriously limited by the insufficient accumulation in the tumor sites. Therefore, herein based on the strong stabilization effects of the metalloid element selenium (Se) on copper (Cu), a photothermic Cu_2-xSe nanoparticle encapsulated with bioresponsive dimethyl maleic anhydride (DMMA@Cu_2-xSe) as a copper-carrier to improve the copper accumulation in tumor is constructed, thus achieving cuproptosis-driven enhancement of thermotherapy. This nanosystem exhibits the enhancement of tumor cellular uptake by a weak acid-triggered charge-switching ability. Next step, the exposed Cu_2-xSe is oxidized and releases divalent copper by high-level oxide. Then, the abundant copper induces more dihydrolipoamide S-acetyltransferase oligomerization to down-regulate FDX1 and tricarboxylic acid cycle-related proteins, which leads to inhibiting aerobic respiration. Cuproptosis-induced mitochondrial damage further improves thermotherapy by up-regulating reactive oxygen species (ROS). In addition, the generated ROS also promotes copper release to strengthen cuproptosis, and eventually improves tumor thermotherapy in turn. In general, DMMA@Cu_2-xSe with sequentially triggered copper-release, efficient cuproptosis, and appropriate photothermal is a self-enhanced nanoplatform for cuproptosis-driven enhancement of thermotherapy.     

Versatile Prodrug Nanoparticles for Acid‐Triggered Precise Imaging and Organelle‐Specific Combination Cancer Therapy

Integration of chemotherapy with photodynamic therapy (PDT) has been emerging as a novel strategy for treatment of triple negative breast cancer (TNBC). However, the clinical translation of this approach is hindered by the unwanted dark toxicity due to the “always‐on” model and low tumor specificity of currently approved photosensitizer (PS). Here, the design of a multifunctional prodrug nanoparticle (NP) is described for precise imaging and organelle‐specific combination cancer therapy. The prodrug NP is composed of a newly synthesized oxaliplatin prodrug, hexadecyl‐oxaliplatin‐trimethyleneamine (HOT), an acid‐activatable PS, derivative of Chlorin e6 (AC), and functionalized with a targeting ligand iRGD for tumor homing and penetration. HOT displays much higher antitumor efficiency than oxaliplatin by simultaneously inducing mitochondria depolarizing and DNA cross‐linking. AC is specifically activated in the orthotopic or metastatic TNBC tumor for fluorescence imaging and PDT, while it remains inert in blood circulation to minimize the dark toxicity. Under the guide of acid‐activatable fluorescence imaging, PDT and chemotherapy can be synergistically performed for highly efficient regression of TNBC. Taken together, this versatile prodrug nanoplatform could achieve tumor‐specific imaging and organelle‐specific combination therapy, which can provide an alternative option for cancer theranostic.     

加入头形式和发光特性对激光诱导肿瘤间质热疗的影响

采用热疗过程中组织物性动态变化的光热模型,数值模拟了分别采用漫射光纤加入头和裸光纤加入头时的激光诱导肿瘤间质热疗(LITT)中热损伤体积的变化,并对实际漫射光纤加入头下发光强度不均匀的影响进行了分析。数值计算结果表明,通常情况下漫射光纤加入头产生的热损伤体积远大于裸光纤时的热损伤体积;裸光纤加入头产生的热损伤区域关于光纤端部不是球对称的,漫射光纤加入头产生的热损伤区域近似呈椭球形;漫射光纤产生的热损伤体积对加入头发光强度的非均匀性不太敏感。可见激光光纤加入头形式和发光特性对激光诱导肿瘤间质热疗具有重要的影响。