Overcoming Challenges of Ovarian Cancer Stem Cells: Novel Therapeutic Approaches

Understanding the genetic and molecular mechanisms of ovarian cancer has been the focus of research efforts working toward the greater goal of improving cancer therapy for patients with residual disease after initial treatment with conventional surgery and neoadjuvant chemotherapy. The focus of this review will be centered on new therapeutic strategies based on Cancer Stem Cells studies of chemoresistant subpopulations, the prevention of metastasis, and individualized therapy in order to find the most successful combination of treatments to effectively treat human ovarian cancer. We reviewed recent literature (1993-2011) of novel treatment approaches to ovarian cancer stem cells. As the focus of ovarian cancer investigation has centered on the cancer stem cell model and the complexities that it presents in the development of effective treatments, the future of treating ovarian cancer lies in utilizing individualized treatment systems that include enhancing existing treatments, aiming for novel therapy targets, managing the plasticity of stem cells to induce cellular differentiation, and regulating oncogenic signaling pathways.     

Targeting Protein Kinases: Tools,Approaches and Case Studies in Inflammation

Inflammation Research -     

靶向HSF1在肿瘤治疗中的作用

目前许多热休克蛋白90抑制剂已经用于抗癌的临床试验,这些抑制剂的产生是肿瘤治疗的里程碑,为癌症治疗探索出更多的新方法。高度保守的热休克转录因子1(heat shock factor 1, HSF1)作为转录因子促进热休克蛋白基因的转录和表达,肿瘤细胞比正常细胞更依赖其功能, HSF1对肿瘤的起始和维持是必需的：调控肿瘤细胞异常信号,抑制有丝分裂增加基因组非整倍性,抑制肿瘤细胞发生凋亡和促进肿瘤细胞转移和代谢等。随着很多小分子药物筛选方法不断的发现和运用,目前已有部分以HSF1为靶点的化合物研究报道,主要有槲皮素和雷公藤内酯抑制HSF1,同时减少热休克反应。文章综述了以HSF1为靶点的药物的研究前沿,并分别阐述了这类药物作用特点和机制。     

Targeting Angiogenesis in Advanced Breast Cancer

Angiogenesis, the process of new blood vessel formation, is required for tumor growth and metastasis. There is substantial preclinical and clinical evidence supporting the central role of angiogenesis in tumor formation and metastasis. Thus, the inhibition of angiogenesis may provide more effective treatment for patients with advanced breast cancer. Several chemotherapeutic and hormonal agents routinely used in the treatment of advanced breast cancer have antiangiogenic properties. Novel antiangiogenic agents targeting the vascular endothelial growth factor (VEGF) ligand and receptor tyrosine kinase inhibitors are being developed. Recently, a large phase III clinical trial demonstrated a significant benefit in progression-free survival with the addition of anti-VEGF monoclonal antibody bevacizumab to paclitaxel for first-line treatment of advanced breast cancer. This study established that antiangiogenic therapy is effective in breast cancer, and additional studies of bevacizumab and other antiangiogenic agents are underway. This article reviews the evidence for the role of angiogenesis in breast cancer pathogenesis, the challenges of developing antiangiogenic agents, and current agents in clinical trials.     

Targeting Cancer Stem Cells in Cancer Prevention and Therapy

The cancer stem cell hypothesis is an attractive framework within which one may think about cancer initiation, recurrence, and metastasis, and methods to devise treatment strategies for cancers. Although all cancers do not appear to sustain themselves with cancer stem cells, but also through a dominant cell population, creating strategies for cancer treatment which include cancer stem cells as targets seems reasonable. In this perspective we discuss possible strategies for controlling the viability and tumorigenecity of cancer stem cells, and extend our discussion to strategies approaching the prevention of cancer.     

Cancer Testis Antigens: A Novel Target in Lung Cancer

Lung cancer is the main cause of cancer mortality worldwide. This is mainly due to the fact that it is diagnosed in advanced stage patients, which are no more surgically curable. Consequently, searching for novel treatments and new modalities for early diagnosis offers great promise to improve the clinical outcome. Recently, a new group of antigens, the cancer testis antigens, have been described as possible early diagnostic tools and therapeutic targets in cancer therapy.This review will report emerging evidences of cancer testis antigens deregulation in lung cancer and explore the state of the art of their currently known role and potential as markers for early diagnosis and disease progression and targets of an immunotherapeutic approach aiming to improve the cure rate of this tumor.     

Editorial: Novel Frontiers in Cancer Metastasis

Clinical & Experimental Metastasis -     

Introduction: Novel Frontiers in Cancer Metastasis

Clinical & Experimental Metastasis -     

Targeting regulatory T cell metabolism in disease: Novel therapeutic opportunities

Regulatory T cells (Tregs) are essential for immune homeostasis and suppression of pathological autoimmunity but can also play a detrimental role in cancer progression via inhibition of anti-tumor immunity. Thus, there is broad applicability for therapeutic Treg targeting, either to enhance function, for example, through adoptive cell therapy (ACT), or to inhibit function with small molecules or antibody-mediated blockade. For both of these strategies, the metabolic state of Tregs is an important consideration since cellular metabolism is intricately linked to function. Mounting evidence has shown that targeting metabolic pathways can selectively promote or inhibit Treg function. This review aims to synthesize the current understanding of Treg metabolism and discuss emerging metabolic targeting strategies in the contexts of transplantation, autoimmunity, and cancer. We discuss approaches to gene editing and cell culture to manipulate Treg metabolism during ex vivo expansion for ACT, as well as in vivo nutritional and pharmacological interventions to modulate Treg metabolism in disease states. Overall, the intricate connection between metabolism and phenotype presents a powerful opportunity to therapeutically tune Treg function.     

Novel Approaches to Food Allergy

Food allergies have increased in recent decades. However, they cannot be effectively treated by the current management, which is limited to the identification and avoidance of foods that induce allergies and to the use of medicines for symptoms relief. To meet the medical need of prevention and cure of food allergies, several therapeutic strategies are under investigation. Some newly developed biologics such as anti-IgE antibody and anti-interleukin (IL)-5 antibody directed against significant molecules in the allergic process have shown their potential for the treatment of food allergies. Allergen-specific immunotherapy is the therapy that induces immune tolerance and may reduce the need for conventional medication, severity of allergic symptoms and eliminate hypersensitivity. In this article, clinical studies of immunotherapy via subcutaneous, oral, sublingual, and epicutaneous routes are extensively reviewed for their safety and effectiveness on various food allergies. In addition, to reduce the risk of anaphylaxis and increase toleragenic immunity, many studies are focusing on the modification of traditional allergens used for immunotherapy. Moreover, a Chinese herbal formulation with potential anti-allergic effects is being evaluated for its efficacy in patients with peanut allergy. Although more studies are needed, accumulated data of current studies represent compelling evidence of curative effects of some strategies and give a hope that food allergies are likely to be successfully treated in the future.     

新型药物载体——聚

从分子水平设计，以具有营养和药理功能的精、赖和天冬氨基酸为单体，合成聚合和     

Selective Targeting of Cancer Stem Cells

Although the concept of 'cancer stem cell' was first proposed more then a century ago, it has attracted a great deal of attention recently due to advances in stem cell biology, leading to the identification of these cells in a wide variety of human cancers. There is accumulating evidence that the resistance of cancer stem cells to many conventional therapies may account for the inability of these therapies to cure most metastatic cancers. The recent identification of stem cell markers and advances in stem cell biology have facilitated research in multiple aspects of cancer stem cell behavior. Stem cell subcomponents have now been identified in a number of human malignancies, including hematologic malignancies and tumors of the breast, prostate, brain, pancreas, head and neck, and colon. Furthermore, pathways that regulate self-renewal and cell fate in these systems are beginning to be elucidated. In addition to pathways such as Wnt, Notch and Hedgehog, known to regulate self-renewal of normal stem cells, tumor suppressor genes such as PTEN (phosphatase and tensin homolog on chromosome 10) and TP53 (tumor protein p53) have also been implicated in the regulation of cancer stem cell self-renewal. In cancer stem cells, these pathways are believed to be deregulated, leading to uncontrolled self-renewal of cancer stem cells which generate tumors that are resistant to conventional therapies. Current cancer therapeutics based on tumor regression may target and kill differentiated tumor cells, which compose the bulk of the tumor, while sparing the rare cancer stem cell population. The cancer stem cell model suggests that the design of new cancer therapeutics may require the targeting and elimination of cancer stem cells. Therefore, it is imperative to design new strategies based upon a better understanding of the signaling pathways that control aspects of self-renewal and survival in cancer stem cells in order to identify novel therapeutic targets in these cells.     

Future perspectives: Novel Frontiers in Cancer Metastasis

Clinical & Experimental Metastasis -     

Proteomic Approaches for Biomarker Panels in Cancer

Proteomic technologies remain the main backbone of biomarkers discovery in cancer. The continuous development of proteomic technologies also enlarges the bioinformatics domain, thus founding the main pillars of cancer therapy. The main source for diagnostic/prognostic/therapy monitoring biomarker panels are molecules that have a dual role, being both indicators of disease development and therapy targets.

Proteomic technologies, such as mass-spectrometry approaches and protein array technologies, represent the main technologies that can depict these biomarkers. Herein, we will illustrate some of the most recent strategies for biomarker discovery in cancer, including the development of immune-markers and the use of cancer stem cells as target therapy.

The challenges of proteomic biomarker discovery need new forms of cross-disciplinary conglomerates that will result in increased and tailored access to treatments for patients; diagnostic companies would benefit from the enhanced co-development of companion diagnostics and pharmaceutical companies.

In the technology optimization in biomarkers, immune assays are the leaders of discovery machinery.     

乳腺癌与微钙化灶的研究进展

微钙化灶是早期诊断乳腺癌的一个常见的影像学表现。本文通过回顾近期关于乳腺癌与微钙化的关系的相关研究,来对乳腺癌微钙化灶的诊断方法以及微钙化灶与乳腺癌的恶性程度、病理类型和预后的关系进行综述,以期发现未来乳腺癌微钙化灶的研究方向以及乳腺癌微钙化灶的临床意义。结果本文发现微钙化灶与乳腺癌的关系还有待发掘,因此进一步的和更全面的研究是有必要的,从而更好地发掘微钙化灶作为一个诊断与判断预后的指标的意义,并通过对微钙化灶发生机制的研究来更好地揭示乳腺癌组织生物学性质的变化。     

Survivin反义核酸对SMMC-7721细胞增殖和凋亡的影响

Survivin是凋亡抑制蛋白（IAP）家族的一个成员，具有强大的抗细胞凋亡功能，在几乎所有肿瘤组织中特异性表达，而在正常成年终末分化组织中低表达甚至不表达。本研究针对Survivin mRNA序列设计了反义寡核甘酸，RT—PCR检测表明，该序列反义寡核苷酸可明显降低细胞中survivin基因的mRNA含量；Western印迹显示Survivin蛋白水平也被降低。MTT比色实验法检测结果说明人Survivin反义寡核苷酸抑制SMMC-7721细胞增殖，抑制率为43％，远高于无义寡核苷酸组和空白对照组。反义寡核苷酸还显著增强SMMC-7721细胞对于抗肿瘤药高三尖杉酯碱的敏感性，TUNEL法检测结果显示，在较低高三尖杉酯碱浓度下，反义寡核苷酸转染细胞的凋亡率明显高于其它对照组。本研究结果提示，survivin表达的靶向抑制有望应用于肿瘤的辅助治疗之中。