微流控芯片在乳腺癌骨转移研究中的应用

乳腺癌骨转移患者死亡率高达70%～80%,目前缺乏有效的治疗药物.微流控芯片技术能够有效模拟骨组织的生化和生物物理微环境,便捷地实现模拟骨微环境中乳腺癌骨转移的研究,这将为探索乳腺癌骨转移的细胞和分子机制、进而进行抗乳腺癌骨转移药物高通量筛选提供有价值的技术方法和平台.本综述简要介绍了乳腺癌骨转移的分子机制和治疗药物研究现状,详细阐述了乳腺癌骨转移的微流控芯片模型,分析了基于微流控芯片技术进行抗乳腺癌骨转移药物高通量筛选的优势和挑战,旨在为乳腺癌骨转移机制研究和药物筛选提供参考.     

基于转录组的肝细胞癌分子分型研究进展

肝细胞癌是恶性程度极高的肿瘤之一,患者的发病率和死亡率都位居恶性肿瘤前列.虽然传统临床病理诊断和分级治疗策略得到了极大的发展,并显著改善了肝细胞癌患者的生存情况,但至今肝细胞癌患者的5年生存率仍然较低.基因测序技术的进步和发展加速了肿瘤基因组学的研究,也帮助科学家认识了肿瘤的异质性及其发生、发展的分子机制.近20年,科学家基于转录组数据提出了许多与病理特征相关的肝细胞癌分子亚型,并对其生物学特性和分子特征进行了深入的挖掘.若能将转录组分子亚型与临床病理分级系统综合考虑,用于肝细胞癌病理诊断和分级治疗,将有望改善病人的生存情况,推进肝细胞癌病人的个体化医疗进程.     

肿瘤骨转移动物模型研究进展

骨转移是乳腺癌、前列腺癌及肺癌等肿瘤的常见并发症,是预后不良的独立危险因素。肿瘤骨转移动物模型是研究骨转移发生机制及评价治疗策略的重要工具。现对骨转移动物模型的研究进展进行综述。     

不同分子分型乳腺癌患者血清IGFBP-3、Angptl-2表达水平及其与骨转移、预后的相关性

摘要 目的：分析不同分子分型乳腺癌患者血清胰岛素样生长因子结合蛋白3（IGFBP-3）、生成素养蛋白2（Angptl-2）表达水平及其与骨转移、预后的相关性。方法：选取2018年3月-2021年3月东南大学附属中大医院收治的128例乳腺癌骨转移患者进行研究,其中包括Luminal A型50例、42例Luminal B型（HER-2阴性）42例、HER-2过表达型16例、三阴性乳腺癌（TNBC）20例,并分析4种分子分型乳腺癌的临床病理特征,同时采用酶联免疫吸附法检测其血清IGFBP-3、Angptl-2表达水平;随访24个月后记录两组患者的预后情况,并采用多因素Logistic模型分析影响4种分子分型乳腺癌骨转移患者预后的独立危险因素,以及血清IGFBP-3、Angptl-2与不同分子分型乳腺癌骨转移患者预后的相关性。结果：Luminal A型、Luminal B型、HER-2过表达型、TNBC型TNM分期、淋巴结转移比较,差异有统计学意义（P＜0.05）。与Luminal A型、Luminal B型、TNBC型乳腺癌骨转移患者相比,HER-2过表达型乳腺癌骨转移患者的血清IGFBP-3表达水平较低,Angptl-2表达水平较高（P＜0.05）。Luminal A型、Luminal B型、HER-2过表达型、TNBC型乳腺癌骨转移患者的死亡率分别为13.46%、38.46%、23.08%、25.00%。多因素Logistic结果显示,TNM分期、淋巴结转移、血清IGFBP-3、Angptl-2均是影响不同分子分型乳腺癌骨转移患者预后的独立危险因素（P＜0.05）。血清IGFBP-3异常高表达提示4种分子分型乳腺癌骨转移患者的不良预后,而Angptl-2表达水平与4种分子分型乳腺癌的预后呈正相关性（P＜0.05）。针对不同分子分型乳腺癌骨转移患者的预后预测中,血清IGFBP-3、Angptl-2、IGFBP-3+Angptl-2均呈现AUC＞0.75。结论：血清IGFBP-3、Angptl-2可作为HER-2过表达乳腺癌骨转移患者的潜在生物标志物;同时还可根据血清IGFBP-3、Angptl-2表达水平预测不同分子分型乳腺癌骨转移患者的预后。     

Ep-cam分子与肿瘤相关研究的进展

随着人们对上皮组织相关癌症的不断认识,Ep-cam分子引起大家越来越大的兴趣.Ep-cam分子作为一个在上皮组织相关癌症中广泛表达的黏附分子,在肿瘤的发生、发展和转移的过程中担当着一个举足轻重的角色,它的相关功能的发现,对人们更好的诊断和治疗这类癌症有着十分重要的作用.就近年来关于Ep-cam分子与肿瘤相关研究的一些进展作一综述.     

氢分子在癌症防治中的应用进展

氢分子作为新型抗氧化剂,对多种由氧化应激和炎症引起的疾病具有良好的治疗效果。肿瘤发病机制复杂,预防和治疗难度大,一些恶性肿瘤的发生与慢性炎症和氧化应激相关,氢分子是否能够通过发挥抗炎症和抗氧化的作用预防癌症的发生并抑制肿瘤的发展得到广泛关注。现有研究表明,氢分子对多种肿瘤具有一定的预防和治疗作用,并能在肿瘤放化疗中起到减副增效的作用,提高患者生存质量。围绕氢分子在癌症预防和治疗方面的发展现状,综述了近年来氢分子在肿瘤研究方面的进展,并对未来的发展方向进行了展望,以期为氢分子在癌症防治中的应用提供参考。     

进展期胃癌靶向治疗的研究进展

胃癌是消化系统最常见的恶性肿瘤之一,全球每年胃癌新发病例数接近百万,严重影响着人类健康.近年来医学领域发展迅速,不管是胃癌的手术方式,还是放疗、化疗等治疗手段均获得了较大提高.但是由于缺乏有效早期诊断方法,大多数胃癌患者确诊时已进入疾病晚期,所以尽管医学技术不断发展,胃癌的死亡率依然居高不下.随着对胃癌分子机制的不断深入研究,一种直接作用于胃癌主要信号转导通路上某一特定靶点的新型治疗方式-分子靶向治疗逐渐成为当前肿瘤研究的热点.目前已有多种单克隆抗体及小分子靶向药物进入临床,用于人体多种肿瘤的治疗并呈现较好疗效.分子靶向治疗的出现为进展期肿瘤患者带来了新的希望.本文主要就进展期胃癌分子靶向治疗现状以及最新研究进展作一综述.     

中药复方BBYNG对乳腺癌骨转移小鼠的作用观察

目的透过对中药复方BBYNG与西药双磷酸盐OSTAC的动物实验研究,观察中药治疗骨转移的疗效。方法参照文献建立高发骨转移的小鼠乳腺癌动物模型后,分别对不同组别的荷瘤小鼠灌喂相当于临床病人服用剂量的BBYNG或OSTAC,对比观察荷瘤小鼠的肿瘤生长、活动状态、生存时间、骨转移及骨破坏的程度等。结果BBYNG可减慢荷瘤小鼠的肿瘤生长,但不能显著缩小肿瘤的体积;可减轻肿瘤骨转移引起的活动障碍和骨破坏,延长生存时间。此结果与作者已进行的临床观察结果相似。结论BBYNG有减轻动物模型肿瘤引起的骨转移和骨破坏、延长荷瘤小鼠生存时间的作用;值得推广应用及开展用于预防肿瘤骨转移的探讨,并深化对其作用机理的研究。     

二甲双胍在肿瘤治疗中的机制研究进展

作为胰岛素增敏剂的降糖药物二甲双胍具有抗肿瘤的多种生物活性,它能够抑制肿瘤细胞的增殖、促进凋亡、增强肿瘤对化疗药物的敏感性、并且能逆转部分肿瘤细胞对化疗药物的耐药性、甚至还能抑制肿瘤新生血管的生成.这些生物功能的实现依赖于AMPK等相关的信号通路的活化,进而负向调控mTOR通路信号分子的表达,再通过转录因子的表达调控相关靶基因的表达.因此这些信号分子的活化或抑制就成为了新的抗肿瘤治疗的靶点.肿瘤干细胞也是近年来研究的一个热点,二甲双胍能直接杀伤某些肿瘤的干细胞,从而达到有效抑瘤的作用.但二甲双胍杀伤肿瘤干细胞的分子机制不明确.另外.二甲双胍联合激素药物治疗肿瘤,可以增加保守治疗的效果.虽然二甲双胍具有显著的抗肿瘤的多重功效,但其具体的分子机制尚未被清晰完整的阐明,有待进一步的研究和证实.     

唑来膦酸联合99Tc-MDP治疗肿瘤多发骨转移的临床价值

目的:探讨唑来膦酸联合99Tc-MDP(云克)治疗多发骨转移瘤的临床价值.方法:将40例确诊为肿瘤伴骨转移的病人,随机分为两组.观察组22例,使用唑来膦酸联合99Tc-MDP治疗;对照组18例,单独使用99Tc-MDP治疗,均治疗3周后比较两组治疗前后骨痛的变化情况、骨转移灶的治疗情况及不良反应的发生情况.结果:观察组和对照组的止痛总有效率分另为95.5％和66.7％,差异有统计学意义(P＜0.05).观察组和对照组骨转移灶的治疗总有效率分别为36.3％和27.7％,差异有统计学意义(P＜0.05).此外,两组治疗过程中均偶见不同程度的发热,但不良反应的发生率并无统计学差异(P＞0.05).结论:唑来膦酸联合99Tc-MDP治疗多发骨转移瘤的止痛效果及骨转移灶的疗效显著优于单纯99Tc-MDP治疗,且毒副作用无明显增加.     

High bone density and bone health

The aim of this paper is to review the main aspects related to high bone density (HBD) as well as to discuss the physiologic mechanisms involved in bone health. There are still no well-defined criteria for identification of individuals with HBD and there are few studies on the topic. Most studies demonstrate that overweight, male gender, black ethnic background, physical activity, calcium and fluoride intake and use of medications such as statins and thiazide diuretics play a relevant and positive role on bone mineral density. Moreover, it is known that individuals with certain diseases such as obesity, diabetes, estrogen receptor-positive breast or endometrial cancer have greater bone density than healthy individuals, as well as athletes having higher bone density than non-athletes does not necessarily mean that they have healthy bones. A better understanding of risk and protective factors may help in the management of patients with bone frailty and have applicability in the treatment and in the prevention of osteoporosis, especially intervening on non-modifiable risk factors.     

Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation.

A 25-kDa homodimeric protein was purified from demineralized bovine bone extract and identified as activin A. The bovine bone activin enhanced formation of ectopic bone in rat subcutis when implanted in combination with partially purified bovine bone morphogenetic protein (BMP-2, BMP-3) in collagen/ceramic carrier. The implants, removed at 14 days, contained markedly elevated levels of alkaline phosphatase activity. Histological examination revealed an extensive formation of woven bone with very little cartilage. In contrast, a combination of transforming growth factor-beta 2 and BMP promoted formation of bone with an abundance of cartilage. The implants with BMP alone exhibited some osteoinductive activity, while the implants with activin alone showed no activity. These results demonstrate that bone is a rich source of activin and that activin plays an important role in modulating bone formation.     

From bone biology to bone analysis

Bone development is one of the key processes characterizing childhood and adolescence. Understanding this process is not only important for physicians treating pediatric bone disorders, but also for clinicians and researchers dealing with postmenopausal and senile osteoporosis. Bone densitometry has great potential to enhance our understanding of bone development. The usefulness of densitometry in children and adolescents would be increased if the physiological mechanisms and structural features of bone were given more consideration in the design and interpretation of densitometric studies. This review gives an overview on the most relevant techniques of quantitative noninvasive bone analysis. Furthermore it describes the relationship between bone biology, selected surrogates describing the biological processes and the possibilities of measuring these surrogates specifically and precisely by the different devices. The overall recommendation for researchers in this field is to describe firstly the biological process to be analyzed (bone growth in length, remodeling or modeling, or all together), secondly the bone parameter which describes this process, and thirdly the reason for selecting a special device.     

Enhanced bone screw fixation with biodegradable bone cement in osteoporotic bone model

Purpose: The purpose of this study was to study the potential of novel biodegradable PCL bone cement to improve bone screw fixation strength in osteoporotic bone. Methods: The biomechanical properties of bone cement (ε-polycaprolactone, PCL) and fixation strength were studied using biomechanical tests and bone screws fixed in an osteoporotic bone model. Removal torques and pullout strengths were assessed for cortical, self-tapping, and cancellous screws inserted in the osteoporotic bone model (polyurethane foam blocks with polycarbonate plate) with and without PCL bone cement. Open cell and cellular rigid foam blocks with a density of 0.12 g/cm3 were used in this model. Results: Removal torques were significantly (more than six-fold) improved with bone cement for cancellous screws. Furthermore, the bone cement improved pullout strengths three to 12 times over depending on the screw and model material.?Conclusions: Biodegradable bone cement turned out to be a very potential material to stabilize screw fixation in osteoporotic bone. The results warrant further research before safe clinical use, especially to clarify clinically relevant factors using real osteoporotic bone under human body conditions and dynamic fatigue testing for long-term performance.     

The bone pencil and the bone surgeon

While helpful for preoperative skin markings, methylene blue is washed away by irrigation and tissue fluids during bony reconstruction. The bone pencil is an ideal marker for hard tissue because it is indelible to irrigation. Further, the surgeon may draw with ease in areas of limited access (i.e., sagittal split and intraoral vertical ramus osteotomies). The pencil can be obtained from most art suppliers. No adverse effects from use of the pencil have been noted in any of our patients.     

In vivo bone strain and bone functional adaptation

Mechanistic interpretations of bone cross-sectional shapes are based on the paradigm of shape optimization such that bone offers maximum mechanical resistance with a minimum of material. Recent in vivo strain studies (Demes et al., Am J Phys Anthropol 106 (1998) 87-100, Am J Phys Anthropol 116 (2001) 257-265; Lieberman et al., Am J Phys Anthropol 123 (2004) 156-171) have questioned these interpretations by demonstrating that long bones diaphyses are not necessarily bent in planes in which they offer maximum resistance to bending. Potential limitations of these in vivo studies have been pointed out by Ruff et al. (Am J Phys Anthropol 129 (2006) 484-498). It is demonstrated here that two loading scenarios, asymmetric bending and buckling, would indeed not lead to correct predictions of loads from strain. It is also shown that buckling is of limited relevance for many primate long bones. This challenges a widely held view that circular bone cross sections make loading directions unpredictable for bones which is based on a buckling load model. Asymmetric bending is a potentially confounding factor for bones with directional differences in principal area moments (I(max) > I(min)). Mathematical corrections are available and should be applied to determine the bending axis in such cases. It is concluded that loads can be reliably extrapolated from strains. More strain studies are needed to improve our understanding of the relationships between activities, bone loading regimes associated with them, and the cross-sectional geometry of bones.     

Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption

Although recombinant human bone morphogenetic proteins (BMPs) are used locally for treating bone defects in humans, their systemic effect on bone augmentation has not been explored. We have previously demonstrated that demineralized bone (DB) from ovariectomized (OVX) rats cannot induce bone formation when implanted ectopically at the subcutaneous site. Here we showed in vitro that 17beta-estradiol (E2) specifically induced expression of Bmp6 mRNA in MC3T3-E1 preosteoblastic cells and that bone extracts from OVX rats lack BMPs. Next we demonstrated that 125I-BMP-6 administered systemically accumulated in the skeleton and also restored the osteoinductive capacity of ectopically implanted DB from OVX rats. BMP-6 applied systemically to aged OVX rats significantly increased bone volume and mechanical characteristics of both the trabecular and cortical bone, the osteoblast surface, serum osteocalcin and osteoprotegerin levels, and decreased the osteoclast surface, serum C-telopeptide, and interleukin-6. E2 was significantly less effective, and was not synergistic with BMP-6. Animals that discontinued BMP-6 therapy maintained bone mineral density gains for another 12 weeks. BMP-6 increased in vivo the bone expression of Acvr-1, Bmpr1b, Smad5, alkaline phosphatase, and collagen type I and decreased expression of Bmp3 and BMP antagonists, chordin and cerberus. These results show, for the first time, that systemically administered BMP-6 restores the bone inductive capacity, microarchitecture, and quality of the skeleton in osteoporotic rats.     

Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass

Aging reduces the number of mesenchymal stem cells (MSCs) that can differentiate into osteoblasts in the bone marrow, which leads to impairment of osteogenesis. However, if MSCs could be directed toward osteogenic differentiation, they could be a viable therapeutic option for bone regeneration. We have developed a method to direct MSCs to the bone surface by attaching a synthetic high-affinity and specific peptidomimetic ligand (LLP2A) against integrin α4β1 on the MSC surface to a bisphosphonate (alendronate, Ale) that has a high affinity for bone. LLP2A-Ale induced MSC migration and osteogenic differentiation in vitro. A single intravenous injection of LLP2A-Ale increased trabecular bone formation and bone mass in both xenotransplantation studies and in immunocompetent mice. Additionally, LLP2A-Ale prevented trabecular bone loss after peak bone acquisition was achieved or as a result of estrogen deficiency. These results provide proof of principle that LLP2A-Ale can direct MSCs to the bone to form new bone and increase bone strength.     

Interparietal bone

The paper deals with the presence of interparietal bone in a single or more pieces out of a series of 1,500 skulls of the Anthropology Museum of Anatomy Department, GSVM Medical College, Kanpur. It was found to be present in 0.3% of cases. It has no morphological importance but it certainly has a morphogenetic bearing.