5-ALA, 5-aminolevulinic acid

5 - ALA, 5 - 氨基乙酰丙酸
  • 文章类型: Journal Article
    甲状腺癌,作为最常见的内分泌癌症之一,近年来发病率激增。这很可能是由于其传统诊断方式缺乏特异性和准确性,导致甲状腺结节的过度诊断。虽然有几种治疗选择,它们仅限于手术和131I放射治疗,这些治疗具有显著的副作用,因此不能满足恶性程度非常高的未分化甲状腺癌的治疗需求.利用光吸收的光学成像,折射和散射特性,不仅观察细胞的结构和功能,组织,器官,甚至整个有机体来协助诊断,但也可用于进行光学治疗,以实现甲状腺癌的靶向非侵入性和精确治疗。这些筛选的应用,诊断,和治疗,赋予光学成像在甲状腺癌手术导航领域的潜力。在过去的十年里,光学成像在甲状腺癌诊断和治疗中的研究逐年增长,但是没有发表关于这个主题的全面评论。这里,我们回顾了光学成像在甲状腺癌诊断和治疗中应用的关键进展,并讨论了该技术在临床应用中的挑战和潜力。
    Thyroid cancer, as one of the most common endocrine cancers, has seen a surge in incidence in recent years. This is most likely due to the lack of specificity and accuracy of its traditional diagnostic modalities, leading to the overdiagnosis of thyroid nodules. Although there are several treatment options available, they are limited to surgery and 131I radiation therapy that come with significant side effects and hence cannot meet the treatment needs of anaplastic thyroid carcinoma with very high malignancy. Optical imaging that utilizes optical absorption, refraction and scattering properties, not only observes the structure and function of cells, tissues, organs, or even the whole organism to assist in diagnosis, but can also be used to perform optical therapy to achieve targeted non-invasive and precise treatment of thyroid cancer. These applications of screening, diagnosis, and treatment, lend to optical imaging\'s promising potential within the realm of thyroid cancer surgical navigation. Over the past decade, research on optical imaging in the diagnosis and treatment of thyroid cancer has been growing year by year, but no comprehensive review on this topic has been published. Here, we review key advances in the application of optical imaging in the diagnosis and treatment of thyroid cancer and discuss the challenges and potential for clinical translation of this technology.
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  • 文章类型: Journal Article
    化疗和免疫疗法的结合通过引发免疫原性细胞死亡(ICD)来激发强大的免疫系统,在抑制肿瘤生长和改善免疫抑制肿瘤微环境(ITM)方面显示出巨大的潜力。然而,低劣的药物生物利用度限制了治疗效果。在这里,我们报道了一种通用的生物响应性阿霉素(DOX)基纳米凝胶,可实现肿瘤特异性药物共递送。设计并选择基于DOX的甘露糖纳米凝胶(DMNG)作为示例,以阐明联合化学免疫疗法的机制。不出所料,DMNG表现出显著的胶束稳定性,选择性药物释放和延长生存时间,受益于增强肿瘤通透性和延长血液循环。我们发现由DMNG递送的DOX可以通过促进ICD来诱导强大的抗肿瘤免疫应答。同时,从DMNGs释放的甘露糖被证明在体外和体内对乳腺癌具有强大的协同治疗作用,通过破坏糖酵解和三羧酸循环中的葡萄糖代谢。总的来说,基于DOX的纳米凝胶对肿瘤微环境的调节有望成为一种有效的候选策略,以克服基于ICD的免疫治疗的当前局限性。为免疫调节纳米药物的开发提供了范例。
    The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.
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  • 文章类型: Journal Article
    皮肤癌一直是全球癌症的主要类型。黑色素瘤和非黑色素瘤皮肤癌现在是最常见的皮肤癌类型,已达到流行比例。基于皮肤癌的快速流行,缺乏有效的药物递送系统,必须增加预防或治愈这种疾病的可能方法。
    尽管近年来手术方式和治疗方法取得了很大进展,然而,仍然迫切需要减轻其增加的负担。因此,了解这种皮肤损伤的精确病理生理机制和所有其他因素将有利于开发更有效的治疗方法。
    在这篇评论中,我们解释了关于皮肤癌的发病和发展的新理解,并描述了通过基于聚合物微/纳米载体的治疗方法,突出该领域当前的关键瓶颈和未来前景。在治疗药物/基因递送方法中,基于聚合物载体的系统是最有前途的策略。这篇综述讨论了如何成功地利用聚合物开发用于有效递送抗癌基因和药物的微/纳米系统,克服了与现有常规疗法相关的所有障碍和限制。除了药物/基因传递,还建立了智能聚合物纳米载体平台,用于联合抗癌治疗,包括光动力和光热,和治疗应用。这种最新方法的组合可以促进研究的蓬勃发展及其临床可用性。
    Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease.
    Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies.
    In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.
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  • 文章类型: Journal Article
    5-氨基乙酰丙酸(5-ALA)由于其可忽略的光敏毒性而被批准用于临床光动力疗法(PDT)。然而,5-ALA的疗效受到细胞内生物转化失活和肿瘤细胞潜在DNA修复的限制。受铁离子在5-ALA转化和DNA修复中的关键功能的启发,开发了一种具有细胞内铁离子调节特性的脂质体纳米药物(MFLs@5-ALA/DFO),用于增强5-ALA的PDT,通过共包封5-ALA和DFO(去铁胺,一种特殊的铁螯合剂)进入膜融合脂质体(MFLs)。MFLs@5-ALA/DFO表现出改善的药学行为并且与肿瘤细胞膜快速融合以用于5-ALA和DFO共同递送。MFLS@5-ALA/DFO可以有效地还原铁离子,从而阻止光敏原卟啉IX(PpIX)向血红素的生物转化,实现光敏性的显著积累。同时,铁离子的还原也抑制了DNA修复酶的活性,导致肿瘤细胞DNA损伤加重。我们的研究结果表明,MFLs@5-ALA/DFO有可能用于增强5-ALA的PDT。
    5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.
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  • 文章类型: Journal Article
    BACKGROUND: In glioma surgery, 5-aminolevulinic acid (5-ALA) fluorescence reflects tumor infiltration, and fluorescence-assisted resection correlates with higher removal rates and improved progression-free survival. Recent studies report that a sizable proportion of brain metastases exhibit peritumoral infiltration on the cellular level. There is little information regarding whether 5-ALA is useful to guide surgery in the peritumoral zone in metastases. The aim of this study was to assess histologically whether 5-ALA fluorescence accurately reflects metastatic brain infiltration.
    METHODS: Fluorescence-assisted tumor resection was performed in 27 patients with brain metastases. Patients received 20 mg/kg 5-ALA 3 hours before anesthesia. After resection, biopsy specimens of the surrounding parenchyma were analyzed for 5-ALA fluorescence and histologic evidence of infiltrating tumor cells. The correlation between 5-ALA positivity and immunohistochemical evidence of tumor in the peritumoral zone was also assessed.
    RESULTS: Of 27 metastases, 23 (85%) were 5-ALA positive. For qualitative tissue analysis, 110 of 125 samples were collected. Metastatic infiltration was present in 49 samples with faint or red fluorescence; 33 samples without fluorescence were tumor-free. The presence of metastatic infiltration correlated with fluorescence (P < 0.001). Tumor infiltration correlated with fluorescence (blue fluorescence 0.09% ± 0.04% and red or faint fluorescence 3.26%; P = 0.003).
    CONCLUSIONS: Infiltration of surrounding brain tissue is a common finding in brain metastases in selected primary tumors. 5-ALA fluorescence correlates with tumor cell infiltration and might guide more radical resection.
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  • 文章类型: Journal Article
    尽管有最新的手术辅助工具和工具,手术切除浸润性脑肿瘤仍然是一个挑战。不清晰的边距,水肿区,和渗透行为是总清除量失败的主要原因。此外,肿瘤周围组织的过度切除通常有损害附近功能皮质和皮质下结构的风险,患者的生活质量和术后功能状态有不可接受的下降,以及使患者没有资格接受辅助治疗的风险。清醒手术和术中磁共振成像(ioMRI)是防止功能性脑损伤同时最大程度切除的最有效辅助手段之一。
    我们介绍了2014年7月至2017年2月在Southmead医院(北布里斯托尔NHSTrust)使用ioMRI加减清醒手术进行手术的46例患者系列。设置,患者特征,适应症,肿瘤的类型和大小,手术次数,切除范围,发病率,和生存进行了分析和讨论。
    总的来说,ioMRI检查导致第1组切除+43%,第2组切除+58%。在2级肿瘤中,GTR在第1组中为46%,在第2组中为55%(在对照组中为41%)。在3级肿瘤中,GTR在第1组中为57%,在第2组中为66%(在对照组中为30%)。在4级肿瘤中,第1组的GTR为63%,第2组的GTR为66%(对照组为36%)。就剧院职业而言,ioMRI的使用增加了1/2的手术期;清醒手术的增加意味着使用另一个1/2的手术期.各组之间的发病率没有差异,术后永久性缺陷发生率低(<5%)。与对照组相比,第2组的OS在统计学上更长。
    使用ioMRI和清醒手术对麻醉团队要求很高,工作人员护士,为了病人。然而,低发病率,更高的总切除率,和更长的生存期表明,它的使用是有效的,使更容易接近的所有级别的胶质瘤,我们会认为“复杂”,由于其固有的特征或位置。
    UNASSIGNED: Despite the most recent surgical aids and tools, surgical removal of infiltrating brain tumors remains a challenge. Unclear margins, edematous areas, and infiltrative behavior are the main causes for failing gross total removals. Also, excessive resection of peri-tumoral tissue often carries risks of damaging the nearby functioning cortical and subcortical structures with an unacceptable decrease in patient\'s quality of life and postoperative functional status, and the risk of making patients not eligible to adjuvant treatments. Awake surgery and intraoperative magnetic resonance imaging (ioMRI) are among the most effective aids in preventing damage to functional brain while maximizing the extent of resection.
    UNASSIGNED: We present our series of 46 patients operated on at Southmead Hospital (North Bristol NHS Trust) in between July 2014 and February 2017 using ioMRI plus or minus awake surgery. Setting, patient features, indications, type and size of tumors, surgical times, extent of resection, morbidity, and survival are analyzed and discussed.
    UNASSIGNED: Overall, ioMRI check led to a +43% resections in Group 1 and +58% in Group 2. In grade 2 tumors, GTR was 46% in Group 1 and 55% in Group 2 (41% in control group). In grade 3 tumors, GTR was 57% in Group 1 and 66% in Group 2 (30% in control group). In Grade 4 tumors, GTR was 63% in Group 1, 66% in Group 2 (36% in control group). In terms of theatre occupation, the use of ioMRI added 1/2 operative session; the addition of awake surgery implied the use of another 1/2 operative session. Morbidity did not differ among the groups, with low incidence of permanent post-operative deficits (<5%). Group 2 OS was statistically longer when compared to the control group.
    UNASSIGNED: Using ioMRI together with awake surgery is demanding for the anesthetic team, staff nurses, and for the patient. Nevertheless, low morbidity, greater total resections rates, and longer survival suggest its use is effective in making more approachable gliomas of all grades that we would consider \"complex\" due to their intrinsic features or locations.
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  • 文章类型: Journal Article
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