新疆核试验场周围土壤中90Sr137Cs水平

用放射化学分析方法,对新疆核试验场周围10个调查区和远离核试验场位于上风向的5个对照区采取的土壤样品进行了⁹⁰Sr、¹³⁷Cs分析测定。核试验场周围调查区土壤中⁹⁰Sr累积平均沉降量为1.5×10³Bqm^-2,¹³⁷Cs为4.9×10³Bqm^-2;对照区⁹⁰Sr累积平均沉降量为1.3×10³Bqm^-2,¹³⁷Cs为3.9×10³Bqm^-2。调查区和对照区表层土壤中州⁹⁰Sr,¹³⁷Cs放射性平均水平无显著性差异。通过估算得出了调查区⁹⁰Sr、¹³⁷Cs对居民产生约定有效剂量当量分别为78.3μSv(集体剂量当量负担为23.9人·sv)和270μSv(集体剂量当量负担为82.3人·sv),对照区分别为70.5μSv,(集体剂量当量负担为14.1人·sv)和220μSv(集体剂量当量负担为14.1人·sv)。两个地区居民受到来自核试验产生的⁹⁰Sr和¹³⁷Cs给予人体的内照射剂量当量负担基本上是一样的。可认为⁹⁰Sr、¹³⁷Cs对新疆核试验场周围没有造成严重的局部污染。对居民的身体健康不致于产生不良影响。     

血清CA19-9,CA-50,CEA联合检测在胰腺癌诊断中的应用

目的:探讨血清CA19-9,CA-50,CEA联合检测对胰腺癌的诊断价值。方法:采用酶联免疫测定法和CA-50抗原免疫放射分析法对27例胰腺癌、19例肝癌和37例胃肠癌、30例消化道良性疾病患者血清CA-19、CA-50和CEA水平进行测定,并对胰腺癌、肝癌、胃肠癌及消化道良性疾病患者血清三项标志物的水平进行比较。结果:消化道恶性肿瘤组的血清CA19-9、CA-50、CEA水平明显高于消化道良性疾病组(P<005),尤以胰腺癌为著(P<001)。还发现肿瘤三项标志物联合测定阳性者(CEA>12ng/ml、CA19-9>37u/ml、CA-50>20u/ml三项中两项超过正常值或单项超过其两倍以上者)胰腺癌组占8889%,与其单检阳性率(4444%)相比有显著性差异(P<0005)。肝癌与胃肠癌两组的肿瘤标志物联检阳性率与单检阳性率相比均无显著性差异(P>005)。结论:血清CA19-9、CA-50和CEA联合检测对胰腺癌的诊断有重要价值。可明显提高胰腺癌的确诊率     

Elevated Src family kinase activity stabilizes E-cadherin-based junctions and collective movement of head and neck squamous cell carcinomas

EGF receptor (EGFR) overexpression is thought to drive head and neck carcinogenesis however clinical responses to EGFR-targeting agents have been modest and alternate targets are actively sought to improve results. Src family kinases (SFKs), reported to act downstream of EGFR are among the alternative targets for which increased expression or activity in epithelial tumors is commonly associated to the dissolution of E-cadherin-based junctions and acquisition of a mesenchymal-like phenotype. Robust expression of total and activated Src was observed in advanced stage head and neck tumors (N=60) and in head and neck squamous cell carcinoma lines. In cultured cancer cells Src co-localized with E-cadherin in cell-cell junctions and its phosphorylation on Y419 was both constitutive and independent of EGFR activation. Selective inhibition of SFKs with SU6656 delocalized E-cadherin and disrupted cellular junctions without affecting E-cadherin expression and this effect was phenocopied by knockdown of Src or Yes. These findings reveal an EGFR-independent role for SFKs in the maintenance of intercellular junctions, which likely contributes to the cohesive invasion E-cadherin-positive cells in advanced tumors. Further, they highlight the need for a deeper comprehension of molecular pathways that drive collective cell invasion, in absence of mesenchymal transition, in order to combat tumor spread.     

导引术作用机制及临床应用

通过对导引术起源、作用机制及防病治病文献的总结论述,结合中医学理论与现代研究分析,揭示导引术防病治病的应用价值。导引术具有疏通经脉、行气活血、培护元气、扶正祛邪、舒筋通络及调整阴阳的作用,其精髓体现了中医学"天人相应"的整体观。导引术调摄身心,呼吸吐纳,配合运动和意念,动静结合,动中有静,刚柔并济,成为融合中医学与体育学的理念于一体的绿色、健康的特色疗法。导引术在防病治病方面具有一定的优势与特色,尤其在治未病及运动疗法的应用中彰显出现代医学不可替代的优势。在目前临床大量应用现代医学介入治疗的态势下,导引术为非损伤、免介入的绿色疗法,应当引起临床的关注与重视。     

Collective cell migration of the nephric duct requires FGF signaling

Background : During the course of development, the vertebrate nephric duct (ND) extends and migrates from the place of its initial formation, adjacent to the anterior somites, until it inserts into the bladder or cloaca in the posterior region of the embryo. The molecular mechanisms that guide ND migration are poorly understood. Results : A novel Gata3‐enhancer‐Gfp‐based chick embryo live imaging system was developed that permits documentation of ND migration at the individual cell level for the first time. FGF Receptors and FGF response genes are expressed in the ND, and FGF ligands are expressed in surrounding tissues. FGF receptor inhibition blocked nephric duct migration. Individual inhibitors of the Erk, p38, or Jnk pathways did not affect duct migration, but inhibition of all three pathways together did inhibit migration of the duct. A localized source of FGF8 placed adjacent to the nephric duct did not affect the duct migration path. Conclusions : FGF signaling acts as a “motor” that is required for duct migration, but other signals are needed to determine the directionality of the duct migration pathway. Developmental Dynamics 244:157–167, 2015. © 2014 Wiley Periodicals, Inc.     

Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters

Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases. We directly observed multicolored tumor cell clusters across major stages of metastasis, including collective invasion, local dissemination, intravascular emboli, circulating tumor cell clusters, and micrometastases. Experimentally aggregating tumor cells into clusters induced a >15-fold increase in colony formation ex vivo and a >100-fold increase in metastasis formation in vivo. Intriguingly, locally disseminated clusters, circulating tumor cell clusters, and lung micrometastases frequently expressed the epithelial cytoskeletal protein, keratin 14 (K14). RNA-seq analysis revealed that K14⁺ cells were enriched for desmosome and hemidesmosome adhesion complex genes, and were depleted for MHC class II genes. Depletion of K14 expression abrogated distant metastases and disrupted expression of multiple metastasis effectors, including Tenascin C (Tnc), Jagged1 (Jag1), and Epiregulin (Ereg). Taken together, our findings reveal K14 as a key regulator of metastasis and establish the concept that K14⁺ epithelial tumor cell clusters disseminate collectively to colonize distant organs.During metastasis, cancer cells escape the primary tumor, travel through the circulation, and colonize distant organs. Conventional models of cancer progression propose that each metastasis arises from the clonal outgrowth of a single tumor cell and this conceptual framework is a foundation for models, such as epithelial-mesenchymal transition (EMT) and migratory cancer stem cells (1).Challenging the generality of the single-cell/single-metastasis model are long-standing clinical observations that tumor cell clusters (also termed “tumor clumps”) are also observed across the stages of metastasis. Tumor cell clusters are detected in the bloodstream of cancer patients (2), clusters can efficiently seed metastases (3), and though rare, circulating tumor cell (CTC) clusters have prognostic significance (4, 5). Furthermore, metastases are composed of multiple genetically distinct tumor cell clones, in mouse models of breast, pancreas, and small cell carcinoma (5–7), and in human metastatic prostate cancer patients (8). Taken together, these observations provide accumulating evidence that tumor cell clusters contribute to metastasis. However, they leave unresolved two important questions: how do tumor cell clusters emerge from the primary tumor, and which molecular features identify cell clusters that metastasize?An important clinical observation is that cancer cells invade the surrounding stroma as cohesive clusters in the majority of epithelial tumors, a process termed “collective invasion” (9, 10). In breast cancer, collective invasion is facilitated by invasive leader cells, a subpopulation of tumor cells that highly express keratin 14 (K14) and other basal epithelial markers (11). K14⁺ cells are migratory, protrusive, and lead trailing K14⁻ cells, while maintaining cell–cell cohesion and E-cadherin–based cell contacts.In this study, we sought to understand how these K14⁺ cells exit collective invasion strands in the primary tumor and travel to distant organs (12). One hypothesis is that collective invasion is an intermediate step toward eventual single-cell dissemination and monoclonal metastasis. However, tumor cell clusters are detected in circulation (5) and primary human breast tumors can disseminate collectively into the surrounding extracellular matrix in ex vivo assays (13–15). These data prompted an alternative hypothesis, that collectively invading K14⁺ cancer cells could initiate and complete the metastatic process as a cohesive multicellular unit. Here we define the clonal nature of metastases in a spontaneous mouse model of metastasis to the lungs (16, 17), in which the predominant invasive form in the primary tumor is collective invasion strands led by K14⁺ cells (11). We establish that the majority of metastases arise from polyclonal seeds, and show that disseminated tumor cell clusters are predominantly composed of K14⁺ cells. We propose a mechanism for polyclonal metastasis via the collective invasion, dissemination, and colonization of clusters of K14⁺ cancer cells.     

Connectivity Defects and Collective Assemblies in Model Metallo‐Supramolecular Dual‐Network Hydrogels

Double network hydrogels are composed of chemical and physical bonds, whose influences on the macroscopic material properties are convoluted. To decouple these, a model dually crosslinked network with independently tunable permanent and reversible crosslinks is introduced. This is realized by interlinking linear and tetra‐arm poly(ethylenegycol) (PEG) precursors with complementary reactive terminal groups. The former also carries a terpyridine ligand at each end, which forms reversible metallo‐supramolecular bonds upon addition of metal ions. These dual networks display different types and amounts of network defects, as studied by light scattering and proton double‐quantum (DQ) NMR. Dynamic light scattering suggests that the network mesh size decreases upon introduction of metal ions, as supported by a decrease of the residual dipolar coupling constant in NMR. Static light scattering indicates larger static inhomogeneities in those networks composed of stronger ions. This is complemented by a fast solid‐like component in the DQ buildup in NMR, attributed to the formation of nanoscopic clusters of charged complexes. The DQ buildup curves also suggest that the presence of strong physical bonds increases the fraction of mobile segments, like loops and dangling ends. This combined study unveils the interplay of chemical and physical bonds toward the formation of a hierarchical structure.