A Red Light Activatable Multifunctional Prodrug for Image‐Guided Photodynamic Therapy and Cascaded Chemotherapy

A multifunctional prodrug, designated as TPP‐L‐GEM, is fabricated to realize image‐guided in situ tumor photodynamic therapy (PDT) with red light activatable chemotherapy. Gemcitabine is conjugated with a fluorescent photosensitizer, meso‐tetraphenylporphyrin (TPP), by a reactive oxygen species cleavable thioketal linker. Under the irradiation of low‐energy red light, TPP can generate singlet oxygen and damage tumor cells by photodynamic therapy. Simultaneously, the thioketal linkage can be cleaved by singlet oxygen and result in a cascaded gemcitabine release, causing sustained cell damage by chemotherapy. With the combination of PDT and cascaded chemotherapy, TPP‐L‐GEM shows significant tumor therapeutic efficacy in vitro and in vivo. Furthermore, the inherent fluorescent property of TPP endows the TPP‐L‐GEM prodrug with noninvasive drug tracking capability, which is favorable for image‐guided tumor therapy.     

Bioresorbable Scaffolds with Biocatalytic Chemotherapy and In Situ Microenvironment Modulation for Postoperative Tissue Repair

New biomaterials with antitumor and tissue repair function have become increasingly important for the postoperative care of melanoma surgery, which could prolong the tumor-free survival of patients while simultaneously facilitating the reconstruction of the trauma tissue. For this purpose, a bioresorbable composite scaffold is designed which is fabricated by depositing therapeutic amorphous calcium carbonate (ACC)-based nanoformulations in gelatin/polycaprolactone (GP) nanofibers via electrospinning. The ACC nanoformulations are integrated with Fe²⁺-preactivated bleomycin to deliver biocatalytically enhanced therapeutic effect while the hydrolysable ACC contents can act as proton scavengers to ameliorate the tumor tissue acidity in situ, leading to sustained inhibition on tumor recurrence and metastasis. The acid-triggered ACC decomposition also releases Ca²⁺ to activate the downstream Wnt/β-catenin signaling pathways, which can cooperate with the healing effect of the GP substrate and accelerate wound regeneration. The nanoengineered scaffold can be useful as a supplementary treatment for the postoperative management of melanoma.     

WISP1 Polymorphisms Contribute to Platinum-Based Chemotherapy Toxicity in Lung Cancer Patients

Platinum-based chemotherapy toxicity is always one of the serious problems from which lung cancer patients suffer. The genetic polymorphism of WISP1 was revealed to be associated with susceptibility and platinum-based chemotherapy response in our previous studies. In this study, we aimed to investigate the relationship of WISP1 genetic polymorphisms with platinum-based chemotherapy toxicity in lung cancer patients. A total of 412 lung cancer patients were enrolled in this study, and 28 polymorphisms of the WISP1 gene were genotyped by SequenomMassARRAY. We found that WISP1 polymorphisms (rs2929965, rs2929969, rs2929970, rs2929973 and rs754958) were related to the overall chemotherapy toxicity of lung cancer in subgroup analyses. Rs16904853, rs2929970, rs2977549 and rs2977551 (p = 0.021, 0.028, 0.024, 0.048, respectively) polymorphisms were significantly associated with hematologic toxicity. Rs2929946, rs2929970, rs2977519, rs2977536, rs3739262 and rs754958 (p = 0.031, 0.046, 0.029, 0.016, 0.042, 0.035, respectively) polymorphisms were significantly associated with the gastrointestinal toxicity of lung cancer. Genotypes of WISP1 may be novel and useful biomarkers for predicting platinum-based chemotherapy toxicity in lung cancer patients.     

中青年乳腺癌患者化疗前后性功能状况调查及原因分析

目的：探讨乳腺癌患者化疗后性功能状况，分析其原因，探讨应对措施和策略。方法：在患者自愿、主动配合的情况下，对80例乳腺癌患者在化疗前后应用《乳腺癌性功能调查问卷》进行调查，行统计学分析，对其性功能状况进行评估，并进行原因分析。结果：在接受调查的患者中，所有被调查者均认为患病后有不同程度的性功能障碍，并认为与疾病和治疗有关，还有药物、配偶态度和形体改变等因素可能对性功能有影响。结论：化疗对乳腺癌患者性功能有明显影响，针对患者认为的可能影响因素，需要进行一些相对应的干预措施。     

Preparation and antitumor activity of bFGF-mediated active targeting doxorubicin microbubbles

Characterization and antitumor activity of basic fibroblast growth factor-mediated active targeting doxorubicin microbubbles (bFGF-DOX-MB) were investigated. Pluronic F68 with chemical conjugation of doxorubicin (DOX-P) and peptide KRTGQYKLC-conjugated DSPE–PEG2000 were prepared. bFGF-DOX-MB had a normal distribution of particle size, with average particle size of 2.7 μm. Using A549 mouse model, bFGF-DOX-MB combined ultrasound showed the best inhibition effect on tumor volume growth among all the test groups. Similar conclusion was obtained from experimental measurements of tumor weight change and blood cell count. From the results, chemotherapeutic drug inhibition on tumor growth could be enhanced by local ultrasound combined with active targeting bFGF-DOX-MB, which might provide a potential application for ultrasound-mediated chemotherapy.     

Molecular Encapsulation of Thalidomide with Sulfobutyl Ether-7 β-Cyclodextrin for Immediate Release Property: Enhanced In Vivo Antitumor and Antiangiogenesis Efficacy in Mice

Thalidomide's reported ability to inhibit tumor angiogenesis has led to clinical trials determining its effectiveness in combating various types of cancer. Since thalidomide exhibits low oral bioavailability due to limitations in solubility, inclusion complexation using sulfobutyl ether-7 β-cyclodextrin was used to improve the delivery of thalidomide. Our main goals were to increase the solubility, bioavailability as well as chemical stability of thalidomide through complexation with anionic β-cyclodextrin, to characterize the complex in solid state using differential scanning calorimetry, X-ray powder diffractometry, and to explore thalidomide's antitumorigenic and antiangiogenesis potential when administered orally as free and in combination with cyclodextrin to experimental animals. The aqueous solubility and aqueous alkaline stability of thalidomide was markedly increased by the SBE7βCD complexation. Thalidomide administered orally in combination with SBE7βCD, led to a significant delay in tumor formation as a result of improved cellular drug absorption, distribution through solubilization in experimental animals. The improved pharmacological efficacy of the thalidomide-cyclodextrin complex compared to free thalidomide in mouse melanoma model suggest that such a delivery system may be useful for the improved therapeutics of thalidomide, in vivo.     

吉西他滨联合卡铂作为诱导方案治疗老年不可手术的非小细胞肺癌

Objective:The purpose of this study was to evaluate the efficacy and safety of gemcitabine (GEM) and carboplatin (CBP) used as induction regimen in the treatment of elderly patients with locally advanced unresectable non-small cell lung cancer (NSCLC). Methods: Seventy-eight cases of elderly patients have been cytologically and pathologically confirmed with locally advanced unresectable NSCLC, the age of the patients ranged from 65 to 75 years. The patients were treated with the combined regimen of gemcitabine and cisplatin. GEM 1000 mg/m2 intravenously injected by drip on the 1st, 8th day and the dosage of CBP was AUC 4 that was used on the 1st day, 21 days apart to each cycle, most patients received 2 cycles. Treatment response was evaluated according to the criteria of RECIST (Response Evaluation Criteria in Solid Tumor), the side effect of the regimen was judged based on WHO criteria. Results: Seventy-eight patients were evaluated and received a total of 156 cycles chemotherapy. There were no complete regression that could be observed, but 32 cases had partial regression (PR), 37 cases with no change (NC) and 9 cases with progression disease (PD). The overall response rate was 41.0%. The main side effects were hematological toxicity. Conclusion: The GC regimen could be used as induction treatment for elderly patients with locally advanced unresectable NSCLC, and the regimen could be well tolerated and is safe in terms of side effects.     

重组人p53腺病毒注射液治疗晚期实体肿瘤的安全性和近期疗效评价

目的: 总结重组人p53 腺病毒注射液(rAdp53)治疗的晚期实体肿瘤患者的资料, 初步评价其安全性与疗效。方法: 常规治疗失败的晚期实体肿瘤患者24 例, 其中肾癌5 例, 鼻咽癌4 例, 结直肠癌4 例, 黑色素瘤2 例, 非小细胞肺癌1 例, 食管癌1例, 贲门癌1 例, 胸腺癌1 例, 十二指肠癌1 例, 甲状腺癌1 例, 胰腺癌1 例, 子宫内膜癌1 例, 横纹肌肉瘤1 例。rAd-p53 给药方案为1 ×1012VP/次, 每周1次, 4 次为1 疗程。给药途径包括瘤内注射、支气管内喷洒、腹腔内注射、动脉灌注和静脉滴注。联合化疗18 例, 联合放疗2 例, 联合同期放、化疗1 例, 联合腹部热疗和吉非替尼1 例, 联合免疫治疗1 例,rAd-p53 单药治疗1 例。结果: 24 例患者中因早期进展而停药1 例, 接受1 疗程治疗20 例, 2 疗程治疗2例, 5 疗程治疗1 例。在可评价的21 例中, 部分缓解(PR) 5 例, 稳定(SD) 5 例, 进展(PD) 11 例, 有效率23.8%(5/21), 疾病控制率47.6%(10/21)。常见不良反应为自限性、I ~ II 度注射部位疼痛、寒颤、发热和肌肉酸痛。III 度发热2 例, 联合化疗者发生III ~IV 度骨髓抑制4 例, 骨痛加剧2 例, 一过性低血压1例。结论: 晚期实体瘤患者可耐受rAd-p53 治疗, 有必要进一步设计临床试验, 确定rAd-p53 联合常规治疗的有效性。     

紫杉醇与环磷酰胺分别联合铂类药治疗卵巢癌的对比研究

目的:比较紫杉醇联合铂类药物(TP 方案) 与环磷酰胺加铂类药物(CP 方案) 治疗Ⅲ、Ⅳ期卵巢上皮癌的疗效。方法:化疗方案每一疗程采用2 d 疗法, 每种药物d 1 或d 2 给药, 采用大剂量单次给药。对24 例Ⅲ、Ⅳ期卵巢上皮癌给予TP 方案化疗:紫杉醇剂量为135 mg·m^-2, 溶于5 %GS 500 ml 中,静滴, 3 h, d 1;顺铂(DDP) 75 mg·m^-2, d 2(或卡铂按AUC =5 计算所得的剂量), 前3 ～ 4 个疗程采用腹腔给药, 以后均静脉给药。30 例对照组病人采用环磷酰胺加铂类药为主的CP 方案。环磷酰胺(CTX)600 mg·m^-2, 静注, d 1;阿霉素(ADM) 40 ～60 mg·m^-2, 静注, d 1;长春新碱(VCR) 2 mg, 静注,d 1;DDP 60 ～ 80 mg·m^-2 (或卡铂, 剂量按AUC =5 计算) 。铂类药物用药时间、途径及水化均与TP 方案相同。结果:TP 方案化疗组CR 为8 例, PR 为10例, 总有效率为75 %;CP 方案对照组CR 4 例, PR 8例, 总有效率为40 %, TP 方案化疗组有效率显著高于CP 方案化疗组(P <0.05) 。TP 治疗组中位生存期为41.5 个月, 高于CP 对照组的32.6 个月(P <0.01) 。结论:TP 方案治疗Ⅲ、Ⅳ期卵巢上皮癌疗效显著优于CP 方案。     

3 种CAg 检测方法评价吡喹酮治疗日本血吸虫病疗效的比较

目的: 探讨3 种不同的循环抗原(CAg) 检测方法在日本血吸虫病人经吡喹酮治疗后疗效考核的应用价值。方法: 采用单克隆抗体(MAb) JPG3, 分别建立了Dot-ELISA 、Sandwich-ELISA 和R-IHA 3 种CAg检测方法, 用吡喹酮(50 mg·kg^-1, 顿服) 治疗日本血吸虫病人, 进行治疗后不同时期的同步血清学检测,并评估检测结果。结果: 吡喹酮治疗后半年, 上述3种检测方法的CAg 阴转率分别为75.8 %、72.6 %和43.5 %(P<0.01), 治疗后1 年分别为83.9 %、88.7 %和71.0 %(P<0.05) ;治疗后2 年分别为87.1 %、95.2 %和93.5 %(P >0.05) ;CAg 阳性病例的平均抗原滴度倒数(GMRT) 随治疗后时间的延长逐步下降, 治疗后2 年三种方法均达到各自的最低阳性稀释度。结论: 考核吡喹酮治疗日本血吸虫病人近期(半年或1 年) 疗效, Dot-ELISA 和Sandwich-ELISA 均较好, 但后者在结果判读上较前者更为客观;考核远期(2 年) 疗效, 3 种方法的检测结果无显著性差别;反映CAg 水平的GMRT 在一定程度上亦能评估吡喹酮之疗效。