Antitumor Effects of Orally and Intraperitoneally Administered Chitosan Oligosaccharides (COSs) on S180‐Bearing/Residual Mouse

Chitosan oligosaccharides (COSs) are hydrolysate mixture of chitin and possess various biomedical properties, such as antimicrobial, immunoenhancing, and antitumor effects. Antiproliferation activity of COS and commercially available samples was compared in the terms of A549 and HCT‐116 cells. Ten tumor cells were used to estimate cytotoxicity of COS. Although there were some researches on the antitumor effects of COS, we highlighted the in vivo antitumor activities of COS administrated orally and intraperitoneally on S180‐bearing/residual mouse. Results turned out that in vitro IC₅₀ values of COS were 48.6 ± 7.0 to 1329.9 ± 93.4 μg/mL against 10 different tumor cell lines. Then, the in vivo experiments proved that the inhibition rate was high up to 58.5%. Significant cell death and necrosis were observed in COS‐treated groups by histological analysis. COS stimulated the mRNA expression of tumor necrosis factor alpha. In summary, COS may be considered promising candidate as antitumor functional food or pharmaceutic adjuvant in oncotherapy, especially for patients after surgical resection.     

不同筛查工具对老年肿瘤患者营养筛查的比较

目的：探讨在老年肿瘤患者中合理选择营养风险筛查工具,以便及时实施营养干预,改善由于营养因素所导致的不良临床结局。方法：对130例老年肿瘤患者应用微型营养评价精法（MNA-SF）和患者主观全面评价法（PG-SGA）进行营养筛查,以白蛋白和前白蛋白为标准评定上述工具的灵敏度、特异度。结果：以白蛋白为参考标准,MNA-SF、PG-SGA的灵敏度分别为55.7%、68.3%,特异度分别为45.1%、89.7%。以前白蛋白为参考标准,MNA-SF、PG-SG的灵敏度分别为67.1%、75.2%,特异度分别为51.0%、93.1%。结论：PG-SGA考虑到多个影响营养的复杂问题,使评价结果更接近于肿瘤患者的实际营养状况。较之MNA-SF,PG-SGA更适用于老年肿瘤患者,值得推广。     

Engineering 2D Mesoporous Silica@MXene‐Integrated 3D‐Printing Scaffolds for Combinatory Osteosarcoma Therapy and NO‐Augmented Bone Regeneration

The rising concerns of the recurrence and bone deficiency in surgical treatment of malignant bone tumors have raised an urgent need of the advance of multifunctional therapeutic platforms for efficient tumor therapy and bone regeneration. Herein, the construction of a multifunctional biomaterial system is reported by the integration of 2D Nb₂C MXene wrapped with S‐nitrosothiol (R? SNO)‐grafted mesoporous silica with 3D‐printing bioactive glass (BG) scaffolds (MBS). The near infrared (NIR)‐triggered photonic hyperthermia of MXene in the NIR‐II biowindow and precisely controlled nitric oxide (NO) release are coordinated for multitarget ablation of bone tumors to enhance localized osteosarcoma treatment. The in situ formed phosphorus and calcium components degraded from BG scaffold promote bone‐regeneration bioactivity, augmented by sufficient blood supply triggered by on‐demand NO release. The tunable NO generation plays a crucial role in sequential adjuvant tumor ablation, combinatory promotion of coupled vascularization, and bone regeneration. This study demonstrates a combinatory osteosarcoma ablation and a full osseous regeneration as enabled by the implantation of MBS. The design of multifunctional scaffolds with the specific features of controllable NO release, highly efficient photothermal conversion, and stimulatory bone regeneration provides an intriguing biomaterial platform for the diversified treatment of bone tumors.     

Traceable Nanoparticles with Dual Targeting and ROS Response for RNAi‐Based Immunochemotherapy of Intracranial Glioblastoma Treatment

The chemotherapy of glioblastoma is severely hindered by the immunosuppressive tumor microenvironment, especially the tumor growth factor β (TGF‐β), an immunosuppressive cytokine. In this study, it is proposed to employ RNAi‐based immunomodulation to modify the tumor immune microenvironment and improve the effect of chemotherapy. Herein, a nanotheranostic system (Angiopep LipoPCB(Temozolomide+BAP/siTGF‐β), ALBTA) with dual targeting and ROS response is established for intracranial glioblastoma treatment. The traceable nanoparticles exhibit strong siRNA condensation, high drug loading efficiency, good serum stability, and magnetic property. They can efficiently cross the blood–brain barrier and target to glioblastoma cells via receptor‐mediated transcytosis. The zwitterionic lipid (distearoyl phosphoethanol‐amine‐polycarboxybetaine lipid) in ALBTA promotes endosomal/lysosomal escape, and thus enhances the cytotoxicity of temozolomide and improves gene silencing efficiency of siTGF‐β. ALBTA significantly improves the immunosuppressive microenvironment and prolongs the survival time of glioma‐bearing mice. Moreover, ALBTA can be accurately traced by MRI in brain tumors. The study indicates that this immunochemotherapeutic platform can serve as a flexible and powerful synergistic system for treatment with brain tumors as well as other brain diseases in central nervous system.     

SN-38 loading capacity of hydrophobic polymer blend nanoparticles: formulation,optimization and efficacy evaluation

One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol^®F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4?h.     

Epigenetic Dysregulations in Merkel Cell Polyomavirus-Driven Merkel Cell Carcinoma

Merkel cell polyomavirus (MCPyV) is a small DNA virus with oncogenic potential. MCPyV is the causative agent of Merkel Cell Carcinoma (MCC), a rare but aggressive tumor of the skin. The role of epigenetic mechanisms, such as histone posttranslational modifications (HPTMs), DNA methylation, and microRNA (miRNA) regulation on MCPyV-driven MCC has recently been highlighted. In this review, we aim to describe and discuss the latest insights into HPTMs, DNA methylation, and miRNA regulation, as well as their regulative factors in the context of MCPyV-driven MCC, to provide an overview of current findings on how MCPyV is involved in the dysregulation of these epigenetic processes. The current state of the art is also described as far as potentially using epigenetic dysregulations and related factors as diagnostic and prognostic tools is concerned, in addition to targets for MCPyV-driven MCC therapy. Growing evidence suggests that the dysregulation of HPTMs, DNA methylation, and miRNA pathways plays a role in MCPyV-driven MCC etiopathogenesis, which, therefore, may potentially be clinically significant for this deadly tumor. A deeper understanding of these mechanisms and related factors may improve diagnosis, prognosis, and therapy for MCPyV-driven MCC.     

胰腺实性假乳头状瘤 10 例临床分析

目的：探讨胰腺实性假乳头状瘤（SPTP）的临床特征、治疗及其预后。方法回顾性分析经手术及病理检查证实的10例 SPTP 患者的临床资料。结果10例患者术后恢复良好,均未出现胆瘘、胰瘘及糖尿病等并发症。8例患者行免疫组织化学检测,其中 NSE 阳性8例,阳性表达率为100．0％;Syn、Vim 和 PR 阳性各7例,阳性表达率均为87．5％;Ki-67部分阳性6例,阳性表达率为75．0％;CK 局灶阳性4例,阳性表达率为50．0％;CD99阳性3例,阳性表达率为37．5％;CK18局灶阳性2例,CD10阳性2例,阳性表达率均为25．0％;CD56、α-AT、α-ACT 和CgA 阳性各1例,阳性表达率均为12．5％;EMA 阴性8例,阴性表达率为100．0％。2例患者未行免疫组织化学检测。10例患者随访时间为6～72个月,均未发现肿瘤复发及转移。结论SPTP 是一种潜在低度恶性肿瘤,可能来源于胰腺胚胎多能干细胞,手术切除是首选的治疗方法。     

小肠神经内分泌肿瘤24例临床分析

目的 探讨小肠神经内分泌肿瘤（NETs）的临床特点、治疗方法及预后.方法 对24例小肠神经内分泌肿瘤患者的临床资料进行回顾性分析.结果 分期情况：T1期7例、T2期4例、T3期4例、T4期6例,另3例无法确定.分级情况：G1级10例,G2级7例,NEC 5例,MANEC 2例.免疫组织化学：Syn、CgA、NSE阳性表达率分别为95%、79%、75%.临床表现：上腹疼痛17例,溃疡出血2例,胆系扩张、梗阻性黄疸、瘙痒5例,恶心呕吐、贫血等3例,类癌综合征1例,无症状1例.治疗：18例十二指肠NETs患者中内镜下切除6例,全身姑息化疗1例,胰十二指肠切除11例,其中术后辅助化疗6例;6例空回肠NETs患者中手术切除3例,肝转移灶介入后再行小肠病灶手术切除1例,对症治疗2例.随访：6例十二指肠NETs内镜下切除者均无病生存,11例十二指肠NETs患者术后1例死于心脏疾病,1例死于肺部感染,2例MANEC患者和未行手术治疗的1例NEC患者存活期较短,分别为13个月、10个月、5个月;6例空回肠NETs患者有2例仍然存活,其余4例出现腹腔、肝内广泛播散,均在2年后死亡.结论 小肠神经内分泌肿瘤缺乏特征性临床症状,内镜有助于该病的早期诊断.尽早手术切除肿瘤可提高患者生存率,病理分期和分级与患者的生存预后密切相关.