Regulation of Metastatic Tumor Dormancy and Emerging Opportunities for Therapeutic Intervention

Cancer recurrence and metastasis, following successful treatment, constitutes a critical threat in clinical oncology and are the leading causes of death amongst cancer patients. This phenomenon is largely attributed to metastatic tumor dormancy, a rate-limiting stage during cancer progression, in which disseminated cancer cells remain in a viable, yet not proliferating state for a prolonged period. Dormant cancer cells are characterized by their entry into cell cycle arrest and survival in a quiescence state to adapt to their new microenvironment through the acquisition of mutations and epigenetic modifications, rendering them resistant to anti-cancer treatment and immune surveillance. Under favorable conditions, disseminated dormant tumor cells ‘re-awake’, resume their proliferation and thus colonize distant sites. Due to their rarity, detection of dormant cells using current diagnostic tools is challenging and, thus, therapeutic targets are hard to be identified. Therefore, unraveling the underlying mechanisms required for keeping disseminating tumor cells dormant, along with signals that stimulate their “re-awakening” are crucial for the discovery of novel pharmacological treatments. In this review, we shed light into the main mechanisms that control dormancy induction and escape as well as emerging therapeutic strategies for the eradication of metastatic dormant cells, including dormancy maintenance, direct targeting of dormant cells and re-awakening dormant cells. Studies on the ability of the metastatic cancer cells to cease proliferation and survive in a quiescent state before re-initiating proliferation and colonization years after successful treatment, will pave the way toward developing innovative therapeutic strategies against dormancy-mediated metastatic outgrowth.     

Osteoarthritis as an Umbrella Term for Different Subsets of Humans Undergoing Joint Degeneration: The Need to Address the Differences to Develop Effective Conservative Treatments and Prevention Strategies

Osteoarthritis (OA) of joints such as the knee and hip are very prevalent, and the number of individuals affected is expected to continue to rise. Currently, conservative treatments after OA diagnosis consist of a series of increasingly invasive interventions as the degeneration and pain increase, leading very often to joint replacement surgery. Most interventions are focused on alleviating pain, and there are no interventions currently available that stop and reverse OA-associated joint damage. For many decades OA was considered a disease of cartilage, but it is now considered a disease of the whole multi-tissue joint. As pain is the usual presenting symptom, for most patients, it is not known when the disease process was initiated and what the basis was for the initiation. The exception is post-traumatic OA which results from an overt injury to the joint that elevates the risk for OA development. This scenario leads to very long wait lists for joint replacement surgery in many jurisdictions. One aspect of why progress has been so slow in addressing the needs of patients is that OA has been used as an umbrella term that does not recognize that joint degeneration may arise from a variety of mechanistic causes that likely need separate analysis to identify interventions unique to each subtype (post-traumatic, metabolic, post-menopausal, growth and maturation associated). A second aspect of the slow pace of progress is that the bulk of research in the area is focused on post-traumatic OA (PTOA) in preclinical models that likely are not clearly relevant to human OA. That is, only ~12% of human OA is due to PTOA, but the bulk of studies investigate PTOA in rodents. Thus, much of the research community is failing the patient population affected by OA. A third aspect is that conservative treatment platforms are not specific to each OA subset, nor are they integrated into a coherent fashion for most patients. This review will discuss the literature relevant to the issues mentioned above and propose some of the directions that will be required going forward to enhance the impact of the research enterprise to affect patient outcomes.     

Recent Advances on the Roles of PCSK-9 Inhibitors in the Management of Acute Ischemic Stroke Patients

Acute ischemic stroke (AIS) represents an important cause of disability and death. Since only a minor percentage of patients with AIS are eligible for acute therapy, the management of risk factors is mandatory. An important risk factor of AIS is hyperlipemia. The current guidelines recommend a strict correction of it. Statins are recommended as the first-line treatment, while proprotein convertase subtilin/kexin type 9 (PCSK-9) inhibitors are administered as a second or even third option when the goal for a low-density lipoprotein cholesterol (LDL-C) level is not achieved. PCSK-9 inhibitors effectively decrease the LDL-C levels through the inhibition of PCSK-9-LDL-receptor complex formation. The in-depth understanding of the PCSK-9 protein mechanism in the metabolism of LDL-C led to the development of effective targeted approaches. Furthermore, a better understanding of the LDL-C metabolic pathway led to the development of newer approaches, which increased the therapeutic options. This article aims to offer an overview of the PCSK-9 inhibitors and their mechanism in reducing the LDL-C levels. Moreover, we will present the main indications of the current guidelines for patients with hyperlipemia and for those who have suffered an acute ischemic stroke, as well as the importance of LDL-C reduction in decreasing the rate of a recurrence.     

Green Tea Catechins: Nature’s Way of Preventing and Treating Cancer

Green tea’s (Camellia sinensis) anticancer and anti-inflammatory effects are well-known. Catechins are the most effective antioxidants among the physiologically active compounds found in Camellia sinesis. Recent research demonstrates that the number of hydroxyl groups and the presence of specific structural groups have a substantial impact on the antioxidant activity of catechins. Unfermented green tea is the finest source of these chemicals. Catechins have the ability to effectively neutralize reactive oxygen species. The catechin derivatives of green tea include epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG). EGCG has the greatest anti-inflammatory and anticancer potential. Notably, catechins in green tea have been explored for their ability to prevent a variety of cancers. Literature evidence, based on epidemiological and laboratory studies, indicates that green tea catechins have certain properties that can serve as the basis for their consideration as lead molecules in the synthesis of novel anticancer drugs and for further exploration of their role as pharmacologically active natural adjuvants to standard chemotherapeutics. The various sections of the article will focus on how catechins affect the survival, proliferation, invasion, angiogenesis, and metastasis of tumors by modulating cellular pathways.     

中国煤矿粉尘危害防治技术现状及发展方向

为了解决煤矿综掘工作面粉尘污染难题,以唐口煤矿3110运输巷综掘工作面为研究对象,对压抽风量比r为0.5、0.8、1.2、1.5条件下的多径向涡旋气幕运移及其阻尘效果开展数值模拟研究。结果表明,随着r的减小,控制风流结构的主要因素由惯性转变为抽风负压,气幕保持径向涡旋状态的轴向运移距离及其前部低速紊流区均随之减小,当r减小至0.8及0.5时,能够在掘进作业区域形成轴向阻尘流场,粉尘污染范围也随之减小。结合综掘工作面实际情况,选取r为0.8,经现场应用,掘进机司机前部断面形成了较为完整的轴向阻尘流场,风速减小至0.38~1.19 m/s,掘进机司机处粉尘质量浓度降至63.0 mg/m³。

     

壳聚糖对鱼腥草提取液絮凝除杂效果的研究

研究了壳聚糖用量、p H和温度对鱼腥草提取液絮凝除杂效果的影响,并对其工艺进行了正交实验优化。实验结果表明最佳的工艺条件是壳聚糖用量为0.04g/100m L,提取液p H为6.0,温度为30℃;在此条件下,鱼腥草澄清液的黄酮保留率为80.0%,透光率高达68.1%。该工艺在絮凝除杂的同时又较好地保留了鱼腥草有效成分,具有良好的应用前景。      

塔河油田X区块奥陶系沥青质油井防堵技术研究

塔河油田X片区奥陶系区块油井陆续出现沥青质堵物堵塞油管、生产管线,造成油井停产,对生产造成了严重影响。针对此类问题,对塔河油田X片区奥陶系原油中沥青质的沉积问题进行了综合研究,得到了有效的油井沥青质防堵生产技术。通过对塔河油田X区块奥陶系原油组分、沥青质沉积堵塞物的分析,发现沥青质沉积主要是由于原油组分中饱和烃含量高,胶质沥青质之比过低,由此发展了沥青分散剂解堵、排出段塞堵物、井口流程优化等治堵工艺。通过试验发现,这些工艺较好地解决了沥青质沉积堵塞油井及管线的问题。     

上海世博会信息化运作模式与风险防范的探究

阐述上海世博会信息化运营架构、上海世博会信息化总体框架、世博会信息化运作模式,并分析世博会信息化运作存在的风险,以及上海世博会信息化运作风险的防范取向等内容。     

爆破有毒气体的污染预报

在爆破后很短时间内形成的蘑菇云和缓慢从爆堆中散发出的爆堆溢出气体构成了爆破毒气的总量.依据气体的运动特点,分别把它们看成是瞬时体积源和不规则体积源.溢出气体扩散采用积分烟团模式,通过模型简化及扩散系数修正,建立了露天矿空气污染评价模型,并利用它对大冶铁矿的爆破进行了较为准确的污染预报.     

新型冠状病毒疫情防控与住宅设计和通风探讨

近期新型冠状病毒感染患者较多,全国各地实行社区防控。针对香港淘大花园社区上百人感染SARS的案例,通过对住宅设计和住宅通风的研究分析,提出两者的缺陷和改造措施。通过以上改造措施,预防病毒在住宅内传播和繁殖,保障居家隔离人员健康。