细菌在肿瘤靶向与免疫治疗中应用的研究进展

细菌用于肿瘤治疗虽然是一个传统的研究领域,但在合成生物学理论与技术日趋完善的背景下,以细菌为载体设计新的抗肿瘤靶向与免疫治疗模式,已经形成一个独特的研究方向。特定细菌可以克服物理障碍特异性地靶向和积聚于肿瘤组织中,并可根据临床需要将外源基因导入细菌,实现基因修饰以产生活性蛋白或因子在肿瘤组织中发挥靶向和抗肿瘤免疫效应,从而提高肿瘤治疗的有效性和安全性。同时,细菌疗法不仅可以作为肿瘤治疗的单一疗法,也可与化疗、放疗和免疫治疗联合使用以获得更好的临床疗效。但是,由于肿瘤微环境的多变性与复杂性,需要进一步充分了解相关细菌和肿瘤微环境的免疫特征,进行有针对性的研究,开发出基于细菌的抗肿瘤免疫精准治疗策略,使细菌疗法在临床肿瘤治疗中得到更广泛的应用。     

细菌介导的肿瘤协同治疗策略

随着基因工程和合成生物学的快速发展,以及对宿主病原体相互作用的认识更加深入,细菌在肿瘤治疗中的作用被广泛研究。细菌介导的肿瘤治疗机制主要包括肿瘤特异性靶向、诱发抗肿瘤免疫反应等,通过与化疗、放疗等传统疗法的结合,可以提高抗肿瘤疗效,同时降低对宿主的全身毒性。利用基因工程可获得对肿瘤组织更高靶向性的减毒菌株或细菌衍生物,从而提高肿瘤治疗的有效性和安全性。此外,细菌表面的可修饰性和表面化学偶联的多样性对实现理想载药及多模式抗肿瘤治疗成为可能,尤其是纳米载药体系与细菌结合组装的生物复合纳米递送系统,可克服传统纳米药物靶向性低、难以渗透到肿瘤深部组织的不足。尽管细菌用作抗肿瘤及释药体系的运输载体仍然有很多亟待解决的问题,但细菌在肿瘤区域特异性定植并诱导肿瘤免疫反应的特性以及作为理想药物载体的潜力,为肿瘤治疗提供了一个颇有前景的新范式。     

肿瘤化疗联合免疫治疗从理论基础到临床实践

在过去的几十年里,化疗是肿瘤内科治疗的基石。尽管化疗疗效显著,但维持病情稳定时间不持久。随着对肿瘤免疫学研究的不断深入,近年来肿瘤免疫治疗再次成为热点。与化疗相比,免疫治疗疗效相对缓和,但更为持久。越来越多的研究表明化疗除了对肿瘤细胞的直接杀伤作用,亦可以增加肿瘤细胞的免疫原性,抑制负性免疫信号,改变肿瘤免疫微环境,从而发挥免疫增强作用,为化疗和免疫治疗的联合应用奠定了理论基础。本文根据已知的肿瘤免疫反应机理和近期发现的化疗免疫调节机制,阐述化疗联合免疫治疗的理论基础,并进一步探讨现有的关于联合治疗的基础和临床研究,从而为后续研究指明方向。      

减毒活细菌在肿瘤治疗中的作用

减毒活细菌在作为感染疫苗用于预防感染性疾病的同时，某些细菌抗肿瘤特性及作为粘膜疫苗载体的研究近来受到了空前的重视。综述几种减毒活细菌在肿瘤治疗中的应用，包括卡介苗、梭状芽孢杆菌、伤寒杆菌、单核细胞李斯特菌等抗肿瘤作用的研究进展和主要作用机制。     

减毒活细菌在肿瘤治疗中的作用

减毒活细菌在作为感染疫苗用于预防感染性疾病的同时,某些细菌抗肿瘤特性及作为粘膜疫苗载体的研究近来受到了空前的重视.综述几种减毒活细菌在肿瘤治疗中的应用,包括卡介苗、梭状芽孢杆菌、伤寒杆菌、单核细胞李斯特菌等抗肿瘤作用的研究进展和主要作用机制.     

细菌生物膜在肿瘤生物学进程及治疗应用中的研究进展

细菌生物膜是细菌及其胞外聚合物形成的微生物群体,具有增强抗生素抵抗及抗宿主免疫等能力。肿瘤微环境中的细菌生物膜具有诱导炎症-癌症转化、促进癌细胞增殖转移和增强肿瘤耐药性等作用,影响着肿瘤的生物学进程。此外,细菌生物膜还被证实可协同抗癌药物抑制肿瘤细胞增殖、促进抗癌药物靶向定植及增强宿主免疫功能。本文就细菌生物膜在影响恶性肿瘤发生发展及抗肿瘤治疗中的研究进行综述。     

癌症的免疫基因治疗：从基础到临床

目前,以外科、化疗及放疗为代表的各种恶性肿瘤常规治疗方法已步人一个平台期,恶性肿瘤仍然是全世界范围内导致死亡的首要原因。肿瘤免疫治疗是一种有效的无创治疗方法,自从上世纪60年代开始就得到了广泛重视。然而,传统的肿瘤免疫治疗方法目前面临巨大挑战,因为其精确性及持久性均较差,治疗效果亦不理想。基于基因转导策略的免疫一基因治疗方法方兴未艾,本文将对肿瘤主动免疫治疗中免疫一基因治疗的方法做详细探讨。     

CpG寡核苷酸在肿瘤治疗中的应用研究进展

肿瘤的免疫治疗可以追溯至19世纪后期,当时纽约的一个外科医师William Coley就已开始运用细菌的提取物治疗肿瘤。进入20世纪后,手术、放疗和化疗成为治疗肿瘤的三大手段,肿瘤的免疫治疗却没有得到很好的发展应用。近年来,随着免疫学的迅猛发展,免疫疗法治疗肿瘤引起了人们更多的重视。最近几年,CpG ODN成为肿瘤免疫治疗领域的一个研究热点。研究表明,CpG ODN具有很强的免疫刺激作用,多项动物实验和临床试验证实其具有一定的抗肿瘤作用。     

肿瘤相关粘蛋白分子在肿瘤诊断及治疗中的意义

肿瘤相关蛋白是肿瘤细胞畸型表达的沾蛋白分子,存在大多数腺瘤及上皮细胞来源的肿瘤细胞表面,与肿瘤的发生、发展及预后密切相关。由于这种分子有特殊结构,使其成为免疫应答的靶分子。目前人们利用这种分子制成疫苗,进行多种肿瘤的治疗性研究,为肿瘤的主动特异性免疫治疗提供了一条新途径。     

胸腺素α1在肿瘤治疗中的应用进展

胸腺素α1（Tα1）是氨基端乙酰化的28个氨基酸组成的多肽激素,作为免疫增强剂,除具有免疫刺激作用外,尚有直接的抗病毒和抗肿瘤作用,被广泛用于治疗肿瘤、免疫缺陷性疾病和在老年人及免疫功能低下的病人中用作疫苗的增强剂。Tα1在对肿瘤治疗的辅助放疗及联合化疗, 表现出积极,肯定的作用,能提高缓解率和生率率,促进免疫功能重建,抑制肿瘤的增生和防治肿瘤扩散,,减少治疗的毒副作用以及改善临床症状、提高生活质量。     

PCA3: from basic molecular science to the clinical lab

Prostate cancer is the second leading cause of cancer deaths in men in the United States. Use of the serum prostate specific antigen (PSA) test to screen men for prostate cancer since the late 1980s has improved the early detection of prostate cancer, however low specificity of the test translates to numerous false positive results and many unnecessary biopsies. New biomarkers to aid in prostate cancer diagnosis are emerging and prostate cancer gene 3 (PCA3) is one such marker. PCA3 is a noncoding RNA that is highly over-expressed in prostate cancer tissue compared to benign tissue. A non-invasive test for PCA3 was developed using whole urine collected after a digital rectal exam (DRE). Numerous clinical studies have demonstrated the utility of PCA3 for the diagnosis of prostate cancer and some studies suggest that PCA3 may also have prognostic value. The use of PCA3 in combination with serum PSA and other clinical information enhances the diagnostic accuracy of prostate cancer detection and will enable physicians to make more informed decisions with patients at risk for prostate cancer.     

基因组学在肺癌研究中从基础向临床应用的转化

随着人类基因组计划的完成,应用基因组计划的研究成果探讨肿瘤发生、发展、侵袭转移的分子机理,开发抗肿瘤分子靶向药物,已成为当今肿瘤学领域的前沿和重点课题。第十一届世界肺癌大会有关本领域的研究内容较多,除应用基因芯片研究肺癌癌变、发生、发展的分子机制,以及肺癌的分子病因学外,更多的研究关注应用基因芯片技术获得的肺癌基因表达谱(基于肺癌细胞中癌基因或抑癌基因的变化或新找到的基因)如何向临床应用转化的问题,包括肺癌的分子诊断、早期发现、特异性标志物的筛选、转移的早期诊断、化疗疗效和预后的判断,以及化疗耐药机制的研…     

Dendritic cell-based vaccines: from mouse models to clinical cancer immunotherapy

B and T lymphocytes are the effectors of specific immunity. However, their function is critically dependent on dendritic cells (DC). DC are professional antigen presenting cells that both initiate and modulate the immune response. The recent breakthrough in the generation of DC from their progenitors has stimulated research on DC in both fundamental and clinical immunology. Objective immune response induction has now been reported in clinical studies using DC. In this review we discuss the development and potential of DC-based vaccines to induce antitumor immunity.     

Papillomaviruses and cancer: from basic studies to clinical application

Links between human papillomaviruses (HPVs) and cervical cancer were first suspected almost 30 years ago. DNA of specific HPV types has since been found in almost all cervical cancer biopsies. HPV oncogenes that are expressed in these cells are involved in their transformation and immortalization, and are required for the progression towards malignancy. Epidemiological studies have underlined that HPVs are the main aetiological factor for cervical cancer. But how has this knowledge been translated into the clinic to allow the prevention, screening and treatment of cervical cancer?     

The role of the IGF system in cancer: from basic to clinical studies and clinical applications

Insulin-like growth factors (IGFs) are important mediators of growth, development, and survival, are synthesized by almost any tissue in the body, and their action is modulated by a complex network of molecules, including binding proteins, proteases and receptors, which all comprise the IGF system. Evidence from in vitro and animal studies suggests that overexpression of IGFs by cancer cells and/or the nearby stroma as well as the type IGF-I receptor by the cancer cells may play a significant role in establishing a transformed phenotype in an increasing number of malignancies. More specifically, IGFs may promote cell cycle progression and inhibition of apoptosis either by directly associating with other growth factors or indirectly by interacting with other molecular systems which have an established role in carcinogenesis and cancer promotion, such as the steroid hormones and integrins. In addition, a growing number of epidemiologic studies suggest that increased serum levels of IGFs and/or altered levels of their binding proteins are associated with increased risk for developing several malignancies. These data indicate that IGF dysregulation should now be considered as an important independent factor for cancer risk, and a potential target for novel antineoplastic therapies and/or preventative strategies in high-risk groups.     

Telomerase and telomeres: from basic biology to cancer treatment

The limited capacity to divide is one of the major differences between normal somatic cells and cancerous cells. This 'finite life span' of somatic cells is closely linked to loss of telomeric DNA at telomeres, the 'chromosome caps' consisting of repeated (TTAGGG) sequences. In more than 85% of advanced cancers, this telomeric attrition is compensated by telomerase, 'the immortality enzyme', implying that telomerase inhibition may restore mortality in tumor cells.

This review discusses the progress in research on the structure and function of telomeres and the telomerase holoenzyme. In addition, new developments in telomere/telomerase targeting compounds such as antisense oligonucleotides and G-quadruplex stabilizing substances, but also new telomerase expression-related strategies such as telomerase promoter-driven suicide gene therapy and telomerase immunotherapy will be presented. It will be discussed how these data can be implemented in telomerase-directed therapies.     

Melatonin: from basic research to cancer treatment clinics.

Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger, an indirect antioxidant, as well as an important immunomodulatory agent. In both in vitro and in vivo investigations, melatonin protected healthy cells from radiation-induced and chemotherapeutic drug-induced toxicity. Furthermore, several clinical studies have demonstrated the potential of melatonin, either alone or in combination with traditional therapy, to yield a favorable efficacy to toxicity ratio in the treatment of human cancers. This study reviews the literature from laboratory investigations that document the antioxidant and oncostatic actions of melatonin and summarizes the evidence regarding the potential use of melatonin in cancer treatment. This study also provides rationale for the design of larger translational research-based clinical trials.     

Spectral signatures of colonic malignancies in the mid-infrared region: from basic research to clinical applicability

The process of carcinogenesis in the colon progresses through several overlapping stages, making the evaluation process challenging, as well as subjective. Owing to the complexity of colonic tissues and the search for a technique that is rapid and foolproof for precise grading and evaluation of biopsies, many spectroscopic techniques have been evaluated in the past few decades for their efficiency and clinical compatibility. Fourier-transform infrared spectroscopy, being quantitative and objective, has the capacity for automation and relevance to cancer diagnosis. This article highlights investigations on the application of Fourier-transform infrared spectroscopy (particularly microscopy) in colon cancer diagnosis and parallel developments in data analysis techniques for the characterization of spectral signatures of malignant tissues in the colon.