Differentiation of osteoid-producing cellsin vitro: Possible evidence for the requirement of a microenvironment

Summary Periostea were dissected from 17-day-old chicken embryo calvariae, placed on millipore filters, and cultured on fluid media containing serum or on serum and plasma containing “plasma clots,” in three ways: 1) with the osteogenic layer facing the filter, 2) with the osteogenic layer away from the filter, 3) folded such that the osteogenic layer was in apposition with itself within the fold. The cultures were studied histologically as well as biochemically. Periostea that were cultured folded showed differentiation of osteoblastlike cells after 2 days, and production of osteoid at day 4. Tissues cultured with the osteogenic layer away from the filter demonstrated similar osteoblastic differentiation and osteoid production. Both types of cultures exhibited an increase in histochemically detectable alkaline phosphatase activity over the 4 day culture period that was associated with osteoblasts and the osteogenic area. Periostea cultured with the osteogenic layer facing the filter produced no osteoid. In these cultures, histochemically detectable alkaline phosphatase activity decreased and virtually disappeared over the 4 day culture period. The possibility that the creation of a suitable micro-environment is required for osteodifferentiation in this culture system is discussed.     

Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics

The microenvironment in which cancer resides plays an important role in regulating cancer survival, progression, malignancy and drug resistance. Tumor microenvironment (TME) consists of heterogeneous number and types of cellular and non-cellular components that vary in relation to tumor phenotype and genotype. In recent, non-cellular secreted components of microenvironmental heterogeneity have been suggested to contain various growth factors, cytokines, RNA, DNA, metabolites, structural matrix and matricellular proteins. These non-cellular components have been indicated to orchestrate numerous ways to support cancer survival and progression by providing metabolites, energy, growth signals, evading immune surveillance, drug resistance environment, metastatic and angiogenesis cues. Thus, switching action from pro-cancer to anti-cancer activities of these secreted components of TME has been considered as a new avenue in cancer therapeutics and drug resistance. In this report, we summarize the recent pre-clinical and clinical evidences to emphasize the importance of non-cellular components of TME in achieving precision therapeutics and biomarker study.     

Inflammatory breast cancer: The pathologists' perspective

Inflammatory breast cancer (IBC) is a clinico-pathological entity, which has specific features of inflammation and pathological evidence of cancer, most often involving dermal lymphatics. This review looks at IBC from the pathologists point of view. The diagnostic criteria and differential diagnosis are summarized first. The staging implications are described next. Despite the overall poor prognosis of IBC, it is heterogeneous in terms of most prognostic and predictive factors (such as histological type, grade, receptor status, intrinsic subtype, inflammatory infiltrate). It seems that some molecular features (genes expressed) are unique to IBC, and this may help to identify them as IBC at the molecular level. The key carcinogenetic pathways activated in IBC, the inflammatory pathways present in the disease as well as the relation of IBC to cancer stem cells are also briefly covered. Due to the relative rarity of IBC, preclinical trials are very important in the study of this entity, and models with stromal and microenvironmental elements are expected to outperform the traditional models without these features, as the microenvironment seems to be a key component of IBC.     

排气通风笼具微环境的动态检测

目的 动态检测屏障环境中用于小鼠的新型排气通风笼具(EVC)的微环境指标.方法 测定两种饲养小鼠的EVC笼盒内通风风速和笼盒体积,计算笼盒换气次数.使用刨花垫料时换笼周期设置为7d,使用玉米芯垫料时换笼周期设置为14d,分别在每种换笼周期内每日连续检测笼盒内的噪声、压差、温度、相对湿度和氨浓度指标.结果 两种EVC笼盒内噪声分别为54.2士3.4 db和55.6士4.1 db,笼盒与屏障环境压差分别为-23.1±9.2 Pa和-27.5±11.6 Pa.从换笼周期第1日起,饲养小鼠的EVC笼盒内的温度差、相对湿度和氨浓度都呈现逐步升高的趋势;使用刨花垫料的两种EVC笼盒其第6日的氨浓度分别达到1.28±0.08 mg/m3和1.33±0.15 mg/m3,笼盒内温度分别为23.5±0.27℃和22.8±0.15℃,湿度分别为67.8％±2.2％和70.2％±1.1％;而使用玉米芯垫料的两种EVC笼盒内第12日达到氨浓度分别为1.95±0.46 mg/m3和2.17±0.33 mg/m3,笼盒内温度分别为23.8±0.4℃和24.1±0.2℃,湿度分别为70.3％±1.8％和69.6％±1.8％.结论 使用EVC笼盒饲养小鼠时,刨花垫料采取每6日换笼及玉米芯垫料采取每12日换笼的方案,可以使笼盒内的微环境指标:噪声、压差、温度、湿度和氨浓度,均符合国标GB 14925-2010要求.提示EVC与玉米芯垫料相结合,有助于维持笼盒内微环境稳定,可用于实验动物的生产和相关研究中.     

Bioactive cell-derived matrices combined with polymer mesh scaffold for osteogenesis and bone healing

Successful bone tissue engineering generally requires an osteoconductive scaffold that consists of extracellular matrix (ECM) to mimic the natural environment. In this study, we developed a PLGA/PLA-based mesh scaffold coated with cell-derived extracellular matrix (CDM) for the delivery of bone morphogenic protein (BMP-2), and assessed the capacity of this system to provide an osteogenic microenvironment. Decellularized ECM from human lung fibroblasts (hFDM) was coated onto the surface of the polymer mesh scaffolds, upon which heparin was then conjugated onto hFDM via EDC chemistry. BMP-2 was subsequently immobilized onto the mesh scaffolds via heparin, and released at a controlled rate. Human placenta-derived mesenchymal stem cells (hPMSCs) were cultured in such scaffolds and subjected to osteogenic differentiation for 28 days in vitro. The results showed that alkaline phosphatase (ALP) activity, mineralization, and osteogenic marker expression were significantly improved with hPMSCs cultured in the hFDM-coated mesh scaffolds compared to the control and fibronectin-coated ones. In addition, a mouse ectopic and rat calvarial bone defect model was used to examine the feasibility of current platform to induce osteogenesis as well as bone regeneration. All hFDM-coated mesh groups exhibited a significant increase of newly formed bone and in particular, hFDM-coated mesh scaffold loaded with a high dose of BMP-2 exhibited a nearly complete bone defect healing as confirmed via micro-CT and histological observation. This work proposes a great potency of using hFDM (biophysical) coupled with BMP-2 (biochemical) as a promising osteogenic microenvironment for bone tissue engineering applications.     

What do functional genomics tell us about pathogenesis of AML?

While molecular genetic abnormalities can tell us much about the pathogenesis of acute myeloid leukemia (AML), these molecular genetics do not always explain drug resistance or sensitivity, leaving room for other mechanisms of tumor pathogenesis outside of genetic events. The Beat AML 1.0 project was a multicenter project to sequence and functionally query AML samples against over 120 drugs. The results have helped form disease models on how mutations affect disease phenotype and drug sensitivity and have assisted in identifying gene signature profiles that may facilitate selecting the most effective treatment options. However, there are factors outside of genetic abnormalities that affect disease pathogenesis. For example, tumor-associated macrophages in the tumor microenvironment play a role in pathogenesis and represent therapeutic targets.     

胰腺导管腺癌肿瘤微环境的研究进展

胰腺导管腺癌(PDAC)是一种恶性程度极高、早期难以诊断、预后极差的恶性肿瘤。近年来的研究发现肿瘤微环境及免疫调节与PDAC的发生密切相关,生物学微环境的研究可能为这种致死性癌症的治疗提供新的策略。笔者就PDAC肿瘤微环境研究的最新进展进行综述。     

胰腺星状细胞在胰腺癌治疗中的应用价值研究进展

胰腺癌因其复杂的肿瘤微环境（TME）,具有恶性程度高、进展快、转移早、化疗耐药及无特殊靶向药物等特点。胰腺星状细胞（PSCs）是胰腺的常驻脂质储存细胞,是TME的重要组成部分,靶向TME中的肿瘤-基质串扰已成为一种有前途的抗胰腺癌进展和转移的治疗策略。因此,笔者就PSCs在胰腺癌TME中的相互作用及靶向活化PSCs的潜在治疗应用进行综述,以期为胰腺癌的治疗提供新靶点和新思路。