肿瘤血管活性肠肽受体显像

血管活性肠肽(VIP)是一种由28个氨基酸组成具有多种功能的神经递质,能通过其受体调节正常及肿瘤细胞的增殖和分化。VPAC(VIP受体)广泛存在于各种正常和肿瘤组织中,但其在肿瘤组织中的表达密度远大于正常组织,这为放射性核素标记的血管活性肠肽受体显像奠定基础。此种显像已应用于多种肿瘤的诊断、分期、治疗方案选择与预后评价。     

肿瘤血管活性肠肽受体显像

血管活性肠肽（VIP）是一种由28个氨基酸组成具有多种功能的神经递质,能通过其受体调节正常及肿瘤细胞的增殖和分化,VPAC（VIP受体）广泛存在于各种正常和肿瘤组织中,但其在肿瘤组织中的表达密度远大于正常组织,这为放射性核素标记的血管活性肠肽受体显像奠定基础,此种显像已应用于多种肿瘤的诊断,分期,治疗方案选择与预后评价。     

β-阻断剂与运动能力

体内许多代谢过程的调节,都有儿茶酚胺类激素的参与。这类激素要与一类肾上腺能受体结合后才能发挥其特定的生理作用。这类受体广泛地存在于体内的多种器官中。如:气管、心肌、肝脏、胰、脂肪组织、血管和骨骼肌等。这种受体可以分成α-、β-     

生长抑素受体显像剂99mTc-depreotide的研究进展

99mTc-depreotide是一种新型生长抑素受体显像剂,能与多种肿瘤细胞高表达的生长抑素受体相结合,对肿瘤的良、恶性评估具有很高的特异性和敏感性,可定性、定位诊断多种生长抑素受体阳性肿瘤,特别是对非小细胞肺癌的定位诊断及鉴别诊断更具有临床价值.Depreotide的生物学特点、放射性核素标记、药物体内分布及肿瘤显像等方面的研究都有了新的进展.     

PAR1与PAR4在肿瘤转移中作用的研究进展

以往研究表明,凝血酶通过其细胞表面的受体--蛋白酶活化受体(protease-activated receptors,PARs)影响肿瘤的转移.PAR1是介导凝血酶促肿瘤转移的主要受体,表达于血管内皮细胞上的PAR1通过影响肿瘤血管新生而促进肿瘤转移.近年来研究发现,PAR1表达于多数肿瘤细胞表面,其表达水平往往预示着该细胞侵袭能力的强弱.PAR4在肿瘤转移中的作用报道较少,仅有的几篇报道提示,PAR4在血管内皮细胞中有表达且在血管发育中起作用,但其是否通过影响肿瘤血管新生而参与肿瘤转移还未见报道.同时,PAR4在肿瘤细胞上的表达仅见于肺癌组织,且其表达水平与肺癌患者的生存直接相关,提示PAR4可能是介导凝血酶影响肿瘤转移的另一重要受体.     

Toll样受体4与肿瘤及其放射敏感性的研究进展

Toll样受体4（TLR4）是一类重要的模式识别受体,不但广泛表达于免疫细胞,也表达于各种肿瘤细胞。TLR4通过不同的信号转导机制促进肿瘤的发生、发展、免疫逃逸、凋亡抵抗、转移和侵袭。激活的TLR4在肿瘤微环境中起着重要作用,且高表达的TLR4影响着肿瘤细胞的放射敏感性,进而严重影响肿瘤放疗的效果,对这些机制的研究可以进一步明确放疗的作用靶点,为恶性肿瘤的治疗提供新的手段。     

叶酸受体及其在肿瘤核医学中的应用

叶酸受体是一种在肿瘤细胞膜表面高度表达的蛋白膜受体,有α和β两种亚型。来源于上皮组织的癌组织高度表达α亚型受体,非上皮来源的癌组织主要表达β亚型受体,两种亚型受体对叶酸及其类似物都有很高的亲和力。叶酸受体在几乎所有的卵巢癌和大部分的恶性肿瘤如乳腺癌、宫颈癌、结肠癌、直肠癌、鼻咽癌等中都有表达,同时在正常组织的表达又高度保守。通过对其分类、结构、染色体定位、分布、配体及其在肿瘤核医学中应用的研究,将有助于肿瘤的早期诊断和针对肿瘤细胞的靶向性治疗。     

肿瘤受体显像及介导靶向治疗的研究进展

肿瘤细胞上某些受体常常超量表达,放射性核素标记的配体可与肿瘤细胞上的相应受体特异性结合而使肿瘤得以显像。利用受体的介导作用,使放射性配体进入并杀死肿瘤细胞而行靶向药物治疗。肿瘤受体显像及受体介导靶向治疗得到广泛的研究,在肿瘤的诊断和治疗中有很高价值。     

叶酸受体及其在肿瘤核医学中的应用

叶酸受体是一种在肿瘤细胞膜表面高度表达的蛋白膜受体，有α和β两种亚型。来源于上皮细胞的癌组织高度表达α亚型受体，非上皮来源的癌组织主要表达β亚型受体，两种亚型受体对叶酸及其类似物都有很高的亲和力。叶酸受体在几乎所有的卵巢癌和大部分的恶性肿瘤如乳腺癌、宫颈癌、结肠癌、直肠癌、鼻咽癌等中都有表达，同时在正常组织的表达又高度保守。通过对其分类、结构、染色体定位、分布、配体及其在肿瘤核医学中应用的研究，将有助于肿瘤的早期诊断和针对肿瘤细胞的靶向性治疗。     

肿瘤受体显像及介导靶向治疗的研究进展

肿瘤细胞上某些受体常常超量表达，放射性核素标记的配体可与肿瘤细胞上的相应受体特异性结合而使肿瘤得以显像。利用受体的介导作用，使放射性配体进入并杀死肿瘤细胞而行靶向药物治疗。肿瘤受体显像及受体介导靶向治疗得到广泛的研究，在肿瘤的诊断和治疗中有很高价值。     

Research and clinical potential of receptor based radiopharmaceuticals

Receptors are proteins that have specific binding affinity for substances that produce a physiological event in the body. Receptor-binding radiotracers are being used increasingly to study the function of receptors in health and disease. This review summarizes the proceedings of a symposium on research in the development of receptor-binding radiopharmaceuticals. The key phases in this research include: selection of the receptor system and ligand; synthesis of radiolabeled ligand; validation in animal models; and clinical application. Current research involves a variety of biological systems, such as butyrophenone neuroleptics for dopamine receptors and steroidal estrogens for the estrogen receptor. In the future, it is believed that receptor-binding radiopharmaceuticals will be useful, not only to validate receptor systems in vivo, but also to aid in the diagnosis and therapy of human diseases.     

Ability to repair DNA double-strand breaks related to cancer susceptibility and radiosensitivity

Traditional radiobiology has aimed at elucidating the mechanism of radiosensitivity of cancer cells and normal cells. Because the mechanism of DNA double-strand break (DSB) repair, which is inherently important to radiosensitivity, was unknown, it has been difficult to obtain results applicable to clinical radiotherapy from traditional radiobiology research. Today, however, the molecular mechanism of DNA DSB repair has been elucidated because of the rapid advances in molecular biology. In DNA DSB repair, at least two major repair mechanisms, homologous recombination and nonhomologous end joining (NHEJ) have been reported. In the NHEJ pathway, DSBs are directly, or after processing of the DNA ends, rejoined at an appropriate chromosomal end. DNA-dependent protein kinase (DNA-PK) plays an important role in DNA DSB repair by NHEJ. We have investigated how the ability of repair of DNA DSB influences cancer susceptibility and the radiosensitivity of tumors and normal tissues by focusing on the activity of DNA-PK. In the near future, research on DNA DSB repair mechanism will be able to be applied to research on carcinogenesis, prediction of radiosensitivity of tumors and normal cells, and sensitization of tumor cells.     

高分子纳米材料用于肿瘤放疗增敏的研究进展

放疗是治疗恶性肿瘤的三大常规手段之一,但由于其存在高辐射剂量损伤正常组织和肿瘤细胞辐射抵抗性强等问题,导致治疗后往往达不到预期效果。为提高放疗疗效,并且减少对正常组织的不良作用,探索新型放疗增敏剂及放化疗联合的新策略已成为研究热点。高分子纳米材料凭借其良好的生物相容性和生理稳定性等优点,为提高肿瘤放疗效果开拓了广阔的应用前景。笔者就高分子纳米材料用于放疗增敏的研究进展进行综述。     

谷氨酸与谷氨酰胺类似物PET显像剂研究进展

谷氨酰胺是血浆中浓度最高的氨基酸，肿瘤细胞的生长与增殖依赖于谷氨酰胺及其中间代谢产物（如谷氨酸、乳酸、脯氨酸、氨等），肿瘤细胞的生长速度与细胞内谷氨酰胺和谷氨酸的浓度密切相关，谷氨酰胺与谷氨酸在肿瘤代谢中起着重要作用。肿瘤细胞摄取谷氨酸与谷氨酰胺类似物PET显像剂的机制主要涉及氨基酸转运与蛋白质合成。谷氨酸与谷氨酰胺类似物PET显像剂在肝细胞癌、脑肿瘤、胶质瘤以及其他多种肿瘤的鉴别诊断中具有优势，可以弥补18F-氟脱氧葡萄糖 PET显像的一些不足。笔者主要对谷氨酸与谷氨酰胺类似物PET显像剂的研究进展进行综述。     

Radioiodinated somatostatin analog scintigraphy in small-cell lung cancer.

Somatostatin receptors have been characterized on biopsy specimens from small-cell lung carcinoma (SCLC) and on cultured human SCLC cells. We recently described the in vivo visualization of various somatostatin receptor-positive tumors, such as carcinoids and endocrine pancreatic tumors, after injection of 123I-Tyr-3-octreotide, a radiolabeled somatostatin analog. In the present study, this imaging procedure using 123I-Tyr-3-octreotide is reported in 11 patients with lung tumors. In five of eight patients with SCLC (63%), we were able to demonstrate tumor deposits using 123I-Tyr-3-octreotide scintigraphy. Unexpected metastases were found in two patients. In one of three patients with SCLC in whom tumor was not visualized, nonvisualization may have been caused by tumor necrosis and recent radiotherapy. In one of two patients with malignant small-cell tumors as described by Askin, the neoplasm was visualized. Like SCLC, these tumors are thought to derive from neuroendocrine cells. In one patient, a squamous-cell carcinoma and a bronchial adenoma were not visualized. We conclude that in the majority of patients with SCLC, the tumor and its metastases can be visualized using 123I-Tyr-3-octreotide scintigraphy. However, the value of this new technique in terms of specificity and sensitivity requires further studies in a larger group of patients.     

相分离影响癌症发生发展的研究进展

相分离是细胞内无膜区室形成的主要机制,参与调控细胞代谢、信号转导、基因表达和蛋白质稳态等多种生理过程。近年来,研究人员发现相分离和癌症密切相关,通过影响DNA修复过程,转录调控,致癌基因和抑癌基因的表达,以及癌症中重要的无膜区室的组装等影响癌症的发生发展。本文回顾了相分离的概念、研究历史、生理功能及其与癌症的关系,重点分析了相分离影响癌症发生发展的可能途径,并提出了相分离领域目前存在的局限性和未来可深入研究的方向。     

Antitumorale Wirkung von Interferonen und Interleukinen in Kombination mit Strahlentherapie

BACKGROUND: During the last 2 decades, cytokines such as interferons (IFN) have been used to modulate tumor response in radiotherapy. Initially, the focus was on antiviral and radiosensitizing effects of interferons but increasingly, the function of interferons and interleukins (IL) within the immune response to tumor cells is becoming important. METHOD: The cellular immune response toward tumor cells is reviewed. The role of cytokines in antigen presentation and activation of effector cells and their interactions with radiation are described. Preclinical strategies of the antitumor action of cytokines are presented and discussed based on the induction of IFN-gamma by IL-12. RESULTS: Recent advances in immunology have demonstrated the importance of local interactions between antigen-presenting cells (APC) and effector cells such as natural killer (NK) cells and T-lymphocytes for an effective immune reaction against tumors. Interferons stimulate such interactions, while IL-2 plays a central role in the activation of NK cells and T-lymphocytes. The interactions between APC and effector cells are suppressed by many tumors but can be stimulated by irradiation. Since systemic application of interferons is quite toxic, present strategies aim at local expression, e. g., the induction of IFN-gamma expression in Th1 cells by IL-12. CONCLUSION: The improved understanding of immunologic mechanisms has emphasized the role of the cytokine network in the interaction between tumor cells and effector cells such as NK cells and T-lymphocytes. This opens new possibilities for the application of cytokines as biological response modifiers, which may eventually help widening the therapeutic window in radiotherapy.     

非编码RNA的表观遗传学调控及在肿瘤中的异常表达

非编码RNAs（ncRNAs）在体内广泛存在,它通过表观遗传方式广泛参与多种重要的调控。对其表观遗传学调控机制还有不同观点,如通过采取RNA干扰的原理进行调控,或通过脱腺苷化作用、脱帽作用等导致靶mRNA的不稳定或抑制翻译等。这些作用使ncRNAs在肿瘤细胞中多表达异常并涉及其发生与发展的整个过程。本文综述了该领域的研究进展。     

Double-echo perfusion-weighted MR imaging: basic concepts and application in brain tumors for the assessment of tumor blood volume and vascular permeability

Perfusion-weighted magnetic resonance (MR) imaging using contrast agents plays a key role in characterizing tumors of the brain. We have shown that double-echo perfusion-weighted MR imaging (DEPWI) is potentially useful in assessing brain tumors. Quantitative indices, such as tumor blood volume, are obtained using DEPWI, which allows correction of underestimation of tumor blood volume due to leakage of contrast agents from tumor vessels, in addition to simultaneous acquisition of tumor vessel permeability. This article describes basic concepts of DEPWI and demonstrates clinical applications in brain tumors.     

核受体在肿瘤放疗增敏中作用机制的研究进展

放疗是肿瘤治疗的主要方法之一,但肿瘤存在辐射抗性,且正常组织存在辐射耐受剂量问题,两者严重影响肿瘤的放疗效果。因此,研究辐射增敏新策略以提高肿瘤细胞的辐射敏感性尤其重要。核受体是细胞内含量丰富的一类转录因子超家族,参与机体多种病理生理过程。近年来的研究结果表明,核受体及其相关配体可能参与肿瘤的放疗抵抗,因而核受体可能是肿瘤放疗增敏的新靶点。笔者总结了核受体及相关配体在肿瘤放疗增敏方面的研究进展。