外泌体在血液肿瘤微环境中的作用及其诊治意义

外泌体是细胞外囊泡的一类主要成分，是正常生理情况下组织细胞间信号传递的重要介质；在多种血液肿瘤研究中发现外泌体是骨髓微环境各成分间相互作用的关键载体，由于其广泛存在并含有特定的核酸、蛋白等分子，外泌体被作为潜在的生物标志物和治疗靶点/载体，在血液肿瘤诊治中的重要性近年正逐步受到关注。     

外泌体在胶质瘤中的研究进展

摘 要：胶质瘤是常见的原发性脑肿瘤，具有高侵袭性、高复发性、高致死率的特点。外泌体是由细胞分泌的功能性囊泡结构，普遍存在于生物体液中，其具有广泛的内容物，并参与了多种生理和病理过程，尤其是肿瘤的发生发展。外泌体可诱导受体细胞产生大量的生物学过程，与肿瘤的形成、发展、转移、浸润和耐药性等密切相关。外泌体在胶质瘤的诊断及治疗中的作用也日益受到重视，胶质瘤外泌体的特异性成分可作为诊断和预测生物标志物，外泌体也可作为运送抗癌药物的载体，经修饰的外泌体可以用于胶质瘤的免疫治疗。本文综述了外泌体在胶质瘤进展中的重要作用及其对诊断和新治疗策略发展的意义。     

外泌体在白血病中的研究进展

外泌体（exosomes，Exs）是多种细胞在正常及病理状态下均能分泌的微小囊泡，直径约40~100 nm，外泌体包含了丰富的蛋白质、miRNA以及RNA片段。近几年的研究表明外泌体可参与白血病的发生发展，在白血病的诊断和治疗中发挥作用。外泌体可通过影响细胞增殖、凋亡和自噬，调节骨髓微环境，促进血管生成及抑制骨髓造血等多方面促进白血病的发生发展。外泌体还可作为白血病的生物标志物，作为白血病的治疗靶点以及影响白血病耐药等。本文就外泌体的形成、组成和功能及近年来外泌体在白血病中的作用进行综述。     

白血病微环境中外泌体的研究进展

外泌体是由多种活细胞分泌的广泛分布于多种体液中的微囊泡结构,携带有亲本细胞来源的核酸、蛋白质和脂质等生物信息分子,是细胞间的通讯载体。外泌体在肿瘤进展中起重要作用,参与肿瘤细胞的增殖、迁移、免疫逃逸及血管生成等。在血液系统中,外泌体涉及白血病细胞及周围环境之间的串扰,促进白血病微环境的形成并充当免疫调节剂,是其治疗研究的潜在方向。文章就外泌体的生物学特性及其在白血病肿瘤微环境和免疫调节中的作用进行综述。     

外泌体在癌症诊治中的作用与机制

外泌体是一种新型的癌症生物标志物，它由所有体液中各种活细胞分泌的双层纳米囊泡构成，含有丰富的蛋白质、DNA、mRNA和非编码RNA。目前外泌体被认为是细胞间通讯的另一种机制，参与细胞间交换蛋白质、脂质和遗传物质。越来越多的研究表明，外泌体在肿瘤的发生、生长、进展、转移、耐药性和免疫逃逸中发挥重要作用。在本文中，我们根据外泌体生物学的最新进展，详细阐述了外泌体影响肿瘤之间通信的具体机制，并报道了外泌体可能成为癌症诊断中有前途的生物标志物，并代表癌症治疗的新靶点。     

肿瘤来源外泌体抗肿瘤免疫研究进展

摘 要：外泌体为体内活细胞释放的微小囊泡，直径范围为30nm~100nm，内含蛋白质、核酸、脂质等，作为细胞间信息交换的载体。不同细胞分泌的外泌体由于其不同的微环境而发挥不同的作用。肿瘤细胞分泌的外泌体对荷瘤体的免疫调节起着重要的作用，表现为免疫促进或抑制，主要为抗肿瘤免疫。全文就肿瘤来源外泌体抗肿瘤免疫的研究进展作一综述。     

外泌体在急性髓系白血病中的作用及临床意义

外泌体是活细胞分泌的一种纳米级的脂质双层囊泡,内含核酸(DNA、mRNA、microRNA、lncRNA 等)、蛋白质、脂质等生物大分子。外泌体作为细胞间通信的载体,参与正常细胞的调控,同时参与疾病的发生发展。急性髓系白血病（acute myeloid leukemia,AML）是骨髓造血细胞克隆性增殖的一种恶性血液病,其特征为骨髓造血干细胞恶性增殖、分化受阻和凋亡抑制。有研究表明,外泌体通过构建肿瘤微环境、抑制骨髓造血、促进血管形成、促进AML细胞增殖、抑制AML细胞凋亡,干扰细胞免疫反应等途径参与急性髓系白血病的发生发展。通过监测外周血或者其他体液中的外泌体,可以提高AML的诊断效率、耐药监测及预后判断等。本文就外泌体在AML中的作用及临床意义的最新研究进行综述,为外泌体在AML中研究提供理论基础及新思路。     

外泌体环状RNA在鳞状细胞癌中的表达及作用

摘 要：外泌体作为包含细胞内外相关蛋白质、编码及非编码RNA、DNA等物质的载体,在多种恶性肿瘤中均有表达,且过量生成的外泌体与恶性肿瘤发生显著相关。环状RNA为重要的调控基因表达的非编码RNA,与多种恶性肿瘤的发生及进展密切相关。全文就环状RNA的生物特性、功能及外泌体环状RNA在鳞状细胞癌中的表达及作用的研究进展作一综述。     

外泌体microRNAs在卵巢癌诊断和治疗中作用的研究进展

外泌体microRNAs(miRNAs)在卵巢癌进展的各种过程中发挥重要作用，如卵巢癌细胞增殖、凋亡和侵袭。外泌体miRNAs通过各种途径参与基因表达、信使RNA合成、蛋白生成等，有助于对卵巢癌发病机制的理解。由于miRNAs在血浆外泌体中的有效性，miRNAs可作为新兴的癌症早期检测和治疗评估生物标志物。外泌体miRNAs作为一种信使，在肿瘤微环境中起着重要的作用，越来越多的研究也证实了miRNAs作为靶点治疗卵巢癌的可行性。     

外泌体在癌相关成纤维细胞与肿瘤细胞交互作用中的研究进展

癌相关成纤维细胞（cancer associated fibroblasts, CAF）在肿瘤微环境中起着重要作用,其不仅能影响正常细胞的恶性转化,还促进肿瘤细胞的增殖、侵袭及远处转移。CAF通过物理吸引作用促进癌细胞转移、促进肿瘤血管生成,影响肿瘤细胞的代谢,从而促进恶性侵袭。外泌体在微环境中能够从供体细胞向受体细胞传递分子和遗传物质,是分子在细胞间转移的载体,在CAF与恶性肿瘤细胞沟通中发挥重要作用。CAF分泌外泌体促进肿瘤的发展,肿瘤细胞源性外泌体能激活CAF。外泌体具有作为靶向药物递送载体的潜在作用,外泌体作为生物特异性标志物也可用于癌症的早期检测、诊断和预后,具有较好的临床应用前景。     

贝伐珠单抗在恶性脑水肿治疗中的应用

以贝伐珠单抗为主的抗血管生成药物通过减少血管通透性和血脑屏障破坏,能有效减轻恶性脑水肿,缓解临床症状,改善患者生命质量。贝伐珠单抗在治疗恶性脑水肿方面取得了积极的疗效,因此被认为是治疗恶性脑水肿的一种安全、有效的治疗手段。     

A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1

Over a million new cases of cancers are diagnosed each year in the United States and over half of these patients die from these devastating diseases. Thus, cancers cause a major public health problem in the United States and worldwide. Chemotherapy remains the principal mode to treat many metastatic cancers. However, occurrence of cellular multidrug resistance (MDR) prevents efficient killing of cancer cells, leading to chemotherapeutic treatment failure. Numerous mechanisms of MDR exist in cancer cells, such as intrinsic or acquired MDR. Overexpression of ATP-binding cassette (ABC) drug transporters, such as P-glycoprotein (P-gp or ABCB1), breast cancer resistance protein (BCRP or ABCG2) and/or multidrug resistance-associated protein (MRP1 or ABCC1), confers an acquired MDR due to their capabilities of transporting a broad range of chemically diverse anticancer drugs. In addition to their roles in MDR, there is substantial evidence suggesting that these drug transporters have functions in tissue defense. Basically, these drug transporters are expressed in tissues important for absorption, such as in lung and gut, and for metabolism and elimination, such as in liver and kidney. In addition, these drug transporters play an important role in maintaining the barrier function of many tissues including blood-brain barrier, blood-cerebral spinal fluid barrier, blood-testis barrier and the maternal-fetal barrier. Thus, these ATP-dependent drug transporters play an important role in the absorption, disposition and elimination of the structurally diverse array of the endobiotics and xenobiotics. In this review, the molecular mechanism of ATP-dependent solute transport by MRP1 will be addressed.     

Moving beyond symptom management towards cancer rehabilitation for older adults: Answering the 5W's

Older adults with cancer are quickly becoming the largest group of cancer survivors. Chronological age is a poor predictor of cancer treatment outcomes and of the need for rehabilitation services. While newer symptom management systems and assessments are slowly becoming used in the clinic to improve communication between providers and survivors, such assessments are rarely used to trigger a referral to rehabilitation. Cancer rehabilitation for older adults with cancer has the potential to improve the quality of life and decrease disability caused by cancer and its treatments. One barrier to referral to cancer rehabilitation remains an understanding of what cancer rehabilitation is, and who, when, where, and why to refer to rehabilitation services. This report utilizes examples of three popular geriatric, distress and symptom measures to help answer these questions.     

Blood-brain barrier permeability imaging using perfusion computed tomography

Background.

The blood-brain barrier represents the selective diffusion barrier at the level of the cerebral microvascular endothelium. Other functions of blood-brain barrier include transport, signaling and osmoregulation. Endothelial cells interact with surrounding astrocytes, pericytes and neurons. These interactions are crucial to the development, structural integrity and function of the cerebral microvascular endothelium. Dysfunctional blood-brain barrier has been associated with pathologies such as acute stroke, tumors, inflammatory and neurodegenerative diseases.

Conclusions.

Blood-brain barrier permeability can be evaluated in vivo by perfusion computed tomography - an efficient diagnostic method that involves the sequential acquisition of tomographic images during the intravenous administration of iodinated contrast material. The major clinical applications of perfusion computed tomography are in acute stroke and in brain tumor imaging.     

High interstitial fluid pressure - an obstacle in cancer therapy

Many solid tumours show an increased interstitial fluid pressure (IFP), which forms a barrier to transcapillary transport. This barrier is an obstacle in tumour treatment, as it results in inefficient uptake of therapeutic agents. There are a number of factors that contribute to increased IFP in the tumour, such as vessel abnormalities, fibrosis and contraction of the interstitial matrix. Lowering the tumour IFP with specific signal-transduction antagonists might be a useful approach to improving anticancer drug efficacy.     

Biosynthetic and proliferative characteristics of the prostatic epithelium in nodular hyperplasia,in cancer and in the peritumoral area

Close interaction between biosynthetic, proliferative and overall activities of nucleic acids in tumor epithelial cells, on the one hand, and histo-hematic barrier of peritumorous area, on the other, has been investigated. Nucleolar organizer regions in prostate cancer appeared very active and the interaction of histo-hematic barrier components much closer than in nodose hyperplasia. Fibroplastic and sclerotic alterations in stroma adjacent to tumor enhanced. It is significant that profound changes occur in the epithelium-connective tissue system in prostate cancer regions which are morphologically identical with those in nodose hyperplasia. It is suggested that such changes might accompany tumorigenesis as well as precede it. In either situation, said characteristics of histo-hematic barrier of peritumorous area may be instrumental in early detection of prostate cancer, particularly, when puncture biopsies are used.     

Anticancer immunotherapy with perorally effective lentinan

Lentinan is a beta(1-3) glucan clarified to have a life prolonging effect in non-operable, recurrent gastric cancer patients in combination with chemotherapy. The long lasting issue remaining to be resolved has been the ineffectiveness of Lentinan when administered per-orally. Beta(1-3) glucans possess the particulate size around 100-200 microm in aqueous solution which dampered the absorption through abdominal mucosa. Subsequently the particulate size of Lentinan impaired the immunostimulating potency, to induce reductive form of antigen presenting cells, macrophages and dendritic cells relevant for the polarization of Th1/Th2 balance to Th1. The situation is also the case for the clinical benefit of lentinan to reduce the side effect of chemotherapeutic agents such as TS-1, Gemzar, CDDP, known to be a critical dose limiting factor of these agents and to improve quality of life of the patients. Using the modern nano-technology procedures, Mitherapist, containing 15 mg/dl Lentinan, with a particulate size of 0.2 microm able to pass through mucosal barrier was provided. It was found in randomized double blind clinical testing that Mitherapist is effective against allergy by reducing an antigen specific IgE level through polarization to Th1 biased immune response even by per-oral administration. Per oral administration also exhibited the reduced side effect of chemotherapeutic agents such as TS-1, Gemzar, CDDP and greatly improved quality of life of the cancer patients. The role of hypoxia in local neoplastic tissues will be also discussed.     

Current Therapeutic Options for Breast Cancer Central Nervous System Metastases

Opinion statement  Breast cancer metastases to the central nervous system (CNS) has devastating consequences for the individual. As treatment options for metastatic breast cancer expand and as quality of life and overall survival improve, researchers are targeting potential treatments for this sanctuary site. Attention is now being focused on defining the phenotype of breast cancer that has a propensity to metastasize to the CNS. Specific therapies that penetrate the blood brain barrier as well as adjuvant therapies that decrease recurrence in the CNS are currently being investigated. We will review current approaches to the diagnosis, evaluation, and treatment of CNS metastases in breast cancer patients.     

Breast cancer brain metastases

Breast cancer is the most common malignancy in woman in the USA. Metastasis is a major cause of morbidity and mortality in breast cancer patients. Total incidence of brain metastases of breast cancer is about 30%. Because of the improvements in control of systemic disease, for example the successful use of Trastuzumab, and the consequent prolonged life span, the incidence of brain metastases is increasing in breast cancer patients. The progressive neurological disabilities not only impair the quality of life, but also decrease the survival in patients. However, current treatments are of limited effectiveness. This is partially caused by the unique structure of the blood brain barrier. So far very little is known about the mechanisms how breast cancer metastizes to the brain. Some studies showed that ErbB2 overexpression is associated with the brain metastatic phenotype. Other molecules, like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs) and chemokine receptor CXCR4 are also involved in the metastasis of breast cancer cell to the brain. The current review will briefly overview the clinical features of brain metastasis of breast cancer and discusses the relationship of blood brain barrier and ErbB2 signal pathway to brain metastasis in breast cancer.     

Management of paclitaxel-induced neurotoxicity

Paclitaxel exerts its antitumor activity by promoting microtubule assembly and stabilizing microtubules. Microtubules are important for the development and maintenance of neurons. As a consequence, neurotoxicity is one of the drug’s major side effects. The risk of neurotoxicity depends on dose, duration and schedule of paclitaxel. Risk increases for patients with pre-existing conditions that may cause neuropathy (such as alcohol consumption, diabetes, or renal disease) or with simultaneous or prior exposure to other neurotoxic chemotherapy such as platinum-based drugs, vinca alkaloids, immunomodulators, proteasome inhibitors, and epothilones. Patients with paclitaxel-induced neurotoxicity (PINT) experience a constellation of symptoms over the course of treatment and beyond, ranging from mild to severe. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability including paresthesia, dysesthesia, and pain. Proprioceptive and motor effects become apparent as neuropathy becomes more advanced. These symptoms may be prolonged, severe, disabling, relatively resistant to intervention and adversely affect activities of daily living and thereby quality of life. Management is mainly symptomatic and supportive. Despite attempts to minimize PINT with changes in dose, vehicle, delivery systems, infusion schedule and premedication or co-treatment with neuroprotective agents, PINT remains dose-limiting in many instances and is a barrier to achieving the desired clinical response.