Studying the performance of bifurcate cryoprobes based on shape factor of cryoablative zones

Conventional cryosurgical process employs extremely low temperatures to kill tumor cells within a closely defined region. However, its efficacy can be markedly compromised if the same treatment method is administrated for highly irregularly shaped tumors. Inadequate controls of freezing may induce tumor recurrence or undesirable over-freezing of surrounding healthy tissue. To address the cryosurgical complexity of irregularly shaped tumors, an analytical treatment on irregularly-shaped tumors has been performed and the degree of tumor irregularities is quantified. A novel cryoprobe coined the bifurcate cryoprobe with the capability to generate irregularly shaped cryo-lesions is proposed. The bifurcate cryoprobe, incorporating shape memory alloy functionality, enables the cryoprobe to regulate its physical configuration. To evaluate the probe’s performance, a bioheat transfer model has been developed and validated with in vitro data. We compared the ablative cryo-lesions induced by different bifurcate cryoprobes with those produced by conventional cryoprobes. Key results have indicated that the proposed bifurcate cryoprobes were able to significantly promote targeted tissue destruction while catering to the shape profiles of solid tumors. This study forms an on-going framework to provide clinicians with alternative versatile devices for the treatment of complex tumors.     

胃肠道间质瘤临床诊治-附46例临床分析

目的:探讨胃肠间质瘤(Gastrointestinal Stromal Tumor,GIST)的临床特点及诊断及治疗方法。方法:回顾性分析我院1997-2009年收治的46例有完整病历资料的GIST病例,以探讨GIST的主要发生部位、临床表现、诊断和治疗方法。结果:GIST主要发生在胃(60.87%)和小肠(26.09%);主要表现为消化道出血(71.74%),腹痛不适(19.57%),腹部包块(15.22%)等;诊断首选B超(阳性率45.65%)、CT(阳性率100%)和内窥镜检查(阳性率81.09%)。本组手术45例,根治性切除40例,姑息性切除3例,术中活检1例,局部切除1例,1例放弃治疗。所有病例均经病理证实。随访42例,复发死亡11例,带瘤生存8例,无瘤生存21例,3例术后口服格列卫(甲磺伊马替尼,ST1571)的病人已生存8月、14月、18月。结论:目前GIST的治疗仍以手术治疗为主,分子靶向制剂的应用显示了一定的治疗效果。     

Lactate and malignant tumors: A therapeutic target at the end stage of glycolysis

Metabolic aberrations in the form of altered flux through key metabolic pathways are primary hallmarks of many malignant tumors. Primarily the result of altered isozyme expression, these adaptations enhance the survival and proliferation of the tumor at the expense of surrounding normal tissue. Consequently, they also expose a unique set of targets for tumor destruction while sparing healthy tissues. Despite this fact, development of drugs to directly target such altered metabolic pathways of malignant tumors has been under-investigated until recently. One such target is the ultimate step of glycolysis, which, as expected, presents itself as a metabolic aberration in most malignant tumors. Termed “aerobic glycolysis” due to abnormal conversion of pyruvic acid to lactic acid even under normoxia, the altered metabolism requires these tumors to rapidly efflux lactic acid to the microenvironment in order to prevent poisoning themselves. Thus, exposed is a prime “choke-point” to target these highly malignant, frequently chemo- and radio- resistant tumors. This review will focus on current outcomes in targeting lactate efflux in such tumors using glioma as a model, an ongoing project in our laboratory for the past half-decade, as well as supporting evidence from recent studies by others on targeting this “tail-end” of glycolysis in other tumor models.     

Loss of pregnancy-associated plasma protein A extends lifespan in mice

Genetic deletion in mice of pregnancy-associated plasma protein A (PAPP-A), a recently identified metalloproteinase in the insulin-like growth factor system, extends by 30-40% both mean and maximum lifespan with no reduction in food intake or secondary endocrine abnormalities. Furthermore, these mice have markedly reduced incidence of spontaneous tumors. The findings implicate PAPP-A as a critical regulator of lifespan and age-related diseases, and suggest PAPP-A as a possible target to promote longevity.     

DPPA2基因的研究进展

DPPA2（Developmental pluripotency．associatedgene2）是近年来发现的一种在多能性细胞和某些癌组织中特意表达的基因。它与早期胚胎发育密切相关,参与维持胚胎干细胞的多能性及自我更新,还在体细胞重编程为多能性诱导干细胞的过程中发挥了作用。此外,它还是一种新的肿瘤抗原,有望成为某些恶性肿瘤的特异性免疫治疗新靶点。本文就DPPA2的结构、功能,以及它与胚胎发育、恶性肿瘤、体细胞重编程的关系等方面的研究进展做一综述。     

Evaluation of Nanoparticle Uptake in Tumors in Real Time Using Intravital Imaging

Current technologies for tumor imaging, such as ultrasound, MRI, PET and CT, are unable to yield high-resolution images for the assessment of nanoparticle uptake in tumors at the microscopic level^1,2,3, highlighting the utility of a suitable xenograft model in which to perform detailed uptake analyses. Here, we use high-resolution intravital imaging to evaluate nanoparticle uptake in human tumor xenografts in a modified, shell-less chicken embryo model. The chicken embryo model is particularly well-suited for these in vivo analyses because it supports the growth of human tumors, is relatively inexpensive and does not require anesthetization or surgery 4,5. Tumor cells form fully vascularized xenografts within 7 days when implanted into the chorioallantoic membrane (CAM) ⁶. The resulting tumors are visualized by non-invasive real-time, high-resolution imaging that can be maintained for up to 72 hours with little impact on either the host or tumor systems. Nanoparticles with a wide range of sizes and formulations administered distal to the tumor can be visualized and quantified as they flow through the bloodstream, extravasate from leaky tumor vasculature, and accumulate at the tumor site. We describe here the analysis of nanoparticles derived from Cowpea mosaic virus (CPMV) decorated with near-infrared fluorescent dyes and/or polyethylene glycol polymers (PEG) ^{7, 8, 9,10,11}. Upon intravenous administration, these viral nanoparticles are rapidly internalized by endothelial cells, resulting in global labeling of the vasculature both outside and within the tumor^7,12. PEGylation of the viral nanoparticles increases their plasma half-life, extends their time in the circulation, and ultimately enhances their accumulation in tumors via the enhanced permeability and retention (EPR) effect ^{7, 10,11}. The rate and extent of accumulation of nanoparticles in a tumor is measured over time using image analysis software. This technique provides a method to both visualize and quantify nanoparticle dynamics in human tumors.