CD26 a cancer stem cell marker and therapeutic target

Cancer stem cells (CSCs) comprise a tumor subpopulation responsible for tumor maintenance, resistance to chemotherapy, recurrence and metastasis. The identification of this cell group is very important, but there is still no consensus on its characterization. Several CSC markers have been described, like CD133, CD24, CD44 and ALDH1, but more research to identify new markers to facilitate the identification of CSC in a heterogeneous tumoral mass is required. Thus, this article describes the CD26 expression as a CSC marker and the role that it plays in different types of cancer. CD26 expression correlates with some characteristics of CSCs, like the formation of spheres in vitro, formation of new tumors, and resistance to chemotherapy. CD26 is therefore suggested as an auxiliary marker for CSC in different types of cancer, and as a potential therapeutic target.     

Modulation of c-kit expression in pancreatic adenocarcinoma: A novel stem cell marker responsible for the progression of the disease

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of late symptoms and resistance to chemotherapy and radiation therapy. We have investigated the appearance of c-kit, a stem cell marker, in both normal adult pancreatic tissue and in cancerous tissue. Apart from some very pale staining of islets of Langerhans, normal pancreas was devoid of staining with antibodies to c-kit. In contrast, in cancerous tissue that still preserves the overall integrity of the pancreatic tissue, there was a clear labeling in islets of Langerhans, which seemed to be co-localized with insulin containing β cells. In other cases, where the pancreatic tissue was completely deteriorated, intensive labeling was clearly evident in remnants of both the exocrine and the endocrine tissues. The duct cells of the adenocarcinoma were moderately but clearly labeled with antibodies to c-kit. In contrast, in metastasis of PDAC, very intensive labeling of c-kit was evident. The location of KRAS, which is strongly associated with PDAC, was also analyzed at the initial stages of the disease, when islets of Langerhans still preserve their integrity to a large extent. KRAS was found exclusively in islets of Langerhans and overlapped in its location with insulin and c-kit expressing cells. It is suggested that the modulation of the expression of c-kit, visualized by antibodies to the oncogene molecule, may play an important role in the formation and progression of PDAC. The absence of c-kit in normal pancreas and its appearance in PDAC is probably due to a mutational event, which probably allows conversion of the β cells into cancer stem cells (CSC). Co-expression of both c-kit and KRAS, typical markers for CSC with overlapping with insulin in islets of Langerhans, strongly support the notion that β-cells play a central role in the development of PDAC. The use of specific drugs that can attenuate the kinase activity of c-kit or target KRAS expressing cancer cells should be tested in order to attenuate the progression of this lethal disease.     

Reinforcing effect of calcium sulfate cement bovine bone morphogenetic protein on vertebral in the rabbit model of osteoporosis

ObjectiveTo observe reinforcing effect of calcium sulfate cement (CSC) bovine bone morphogenetic protein (bBMP) on vertebral in the rabbit model of osteoporosis.MethodsA total of 48 New Zealand white rabbits were randomly divided into group I (blank control group), group II (CSC injection group), group III (CSC/bBMP injection group) and control group. White rabbit osteoporosis model was established rapidly by using castration method+methylprednisolone candidate. After modeling, groups II, III were given corresponding vertebral body injection material, and 4 animals were sacrificed respectively at 24 h, 6 weeks, 12 weeks after vertebral plasty. Tissue pathological status, vertebral mineral density and vertebral body bone mechanical strength were observed.ResultsVertebral body structure form was normal in the groups II and III. Trabecular bone coarsens, connection and repair were observed in micro fracture and bone defects, bone trabecular connectivity was superior to group I significantly; vertebral body compression strength in the groupI was on the decline, vertebral compression strength in the groups IIand III was on the rise, the largest vertebra. Postoperative BMC and BMD in groups IIand III were incresed, and significantly higher than group I after 6 weeks (P<0.05), BMC and BMD in group III after 12 weeks were higher than the other three groups.ConclusionCompound bBMP CSC has good bone induction. It can improve the three-dimensional construction effect for osteoporosis vertebral trabecula, and can significantly improve the vertebral strength, as a vertebral packing material with good application prospect.     

Adenosine A2A receptors and brain injury: broad spectrum of neuroprotection, multifaceted actions and "fine tuning" modulation

This review summarizes recent developments that have contributed to understand how adenosine receptors, particularly A2A receptors, modulate brain injury in various animal models of neurological disorders, including Parkinson's disease (PD), stroke, Huntington's disease (HD), multiple sclerosis, Alzheimer's disease (AD) and HIV-associated dementia. It is clear that extracellular adenosine acting at adenosine receptors influences the functional outcome in a broad spectrum of brain injuries, indicating that A2A Rs may modulate some general cellular processes to affect neuronal cells death. Pharmacological, neurochemical and molecular/genetic approaches to the complex actions of A2A receptors in different cellular elements suggest that A2A receptor activation can be detrimental or protective after brain insults, depending on the nature of brain injury and associated pathological conditions. An interesting concept that emerges from these studies is A2A R's ability to fine tune neuronal and glial functions to produce neuroprotective effects. While the data presented here clearly highlight the complexity of using adenosinergic agents therapeutically in PD and other neurodegenerative disorders and point out many areas for further inquiry, they also confirm that adenosine receptor ligands, particularly A2A receptor ligands, have many promising characteristics that encourage the pursuit of their therapeutic potential.     

激光光凝眼底联合卵磷脂络合碘片治疗中心性浆液性脉络膜视网膜病变99例疗效观察

目的评价激光光凝眼底联合卵磷脂络合碘片治疗中心性浆液性脉络膜视网膜病变(CSC)的疗效。方法将198例CSC患者212眼根据患者自愿分为两组各99例106眼。对照组采用激光光凝眼底治疗,观察组采用激光光凝眼底联合卵磷脂络合碘片治疗。在治疗1个月和3个月后用Amsler方格表评价视力恢复状况,并比较两组疗效。结果两组治疗后视力较之治疗前明显改善(P<0.05)。观察组治疗1月后视力恢复状况明显好于对照组(P<0.05),3月后两组视力无统计学差异(P>0.05)。观察组总显效率与对照组相比有统计学差异(P<0.05),但总有效率组间无统计学差异(P>0.05)。结论激光光凝眼底联合卵磷脂络合碘片治疗CSC可以帮助患者尽快改善视力状况,提升治疗总显效率,是一种较为理想的治疗手段,值得在临床中推广运用。     

Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model

BACKGROUND & AIMS: The aim was to determine whether adenosine receptors modulate cAMP, intracellular free calcium ([Ca(2+)](i)), and 5-hydroxytryptamine (5-HT) release in human carcinoid BON cells. METHODS: Adenosine receptor (R) mRNA, proteins, and function were identified by Western blots, immunofluorescent labeling, Fluo-4/AM [Ca(2+)](i) imaging, and pharmacologic/physiologic techniques. RESULTS: A1, A2, and A3Rs were present in BON cells and carcinoid tumors. Baseline 5-HT levels increased with adenosine deaminase, activation of A2Rs, and inhibition of A3Rs, whereas A3R activation decreased 5-HT. A2R antagonists or blockade of adenosine reuptake that elevates extracellular adenosine reduced mechanically evoked 5-HT release. In single BON cells, touch elevated [Ca(2+)](i) responses were augmented by adenosine deaminase, A1, and A3R antagonists. CONCLUSIONS: Tonic or mechanically evoked release of endogenous adenosine is a critical determinant of differential activation of adenosine receptors and may have important implications for gut mechanosensory reflexes.     

Modeling of cancer metastasis and drug resistance via biomimetic nano-cilia and microfluidics

Three-dimensional (3D) tissue culture platforms that are capable of mimicking in vivo microenvironments to replicate physiological conditions are vital tools in a wide range of cellular and clinical studies. Here, learning from the nature of cilia in lungs – clearing mucus and pathogens from the airway – we develop a 3D culture approach via flexible and kinetic copolymer-based chains (nano-cilia) for diminishing cell-to-substrate adhesion. Multicellular spheroids or colonies were tested for 3–7 days in a microenvironment consisting of generated cells with properties of putative cancer stem cells (CSCs). The dynamic and reversible regulation of epithelial–mesenchymal transition (EMT) was examined in spheroids passaged and cultured in copolymer-coated dishes. The expression of CSC markers, including CD44, CD133, and ABCG2, and hypoxia signature, HIF-1α, was significantly upregulated compared to that without the nano-cilia. In addition, these spheroids exhibited chemotherapeutic resistance in vitro and acquired enhanced metastatic propensity, as verified from microfluidic chemotaxis assay designed to replicate in vivo-like metastasis. The biomimetic nano-cilia approach and microfluidic device may offer new opportunities to establish a rapid and cost-effective platform for the study of anti-cancer therapeutics and CSCs.