Human serum albumin (HSA) is a biological macromolecule with important physiological functions; abnormal HSA levels are associated with coronary heart disease, multiple myeloma, diabetes, ...nephropathy, neurometabolic disorders, liver cirrhosis and other diseases. Therefore, accurate and quantitative detection of HAS have extremely important research and application value in biological science, molecular biology, clinical medicine and other fields. As for the detection method of HSA, dye-binding method and immune method are the first to be used, and have been applied in clinical detection. In recent years, many new detection technologies have emerged, such as fluorescent probe detection method, nano-materials for HSA detection, biosensor and so on. Although there are many methods developed recently to detect HSA, comprehensive reviews for HSA detection methods are still rare. Thus, writing this review to fill in the blank is in need. In order to highlight the recent progress in the field of HSA detection, in this review, the methods used to detect HSA are summarized and sorted, the advantages and disadvantages of these detection methods are also listed, then the research progress of small molecular fluorescence probe method is emphatically introduced in this paper. Then, we briefly discussed the challenges and future development directions in this field.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Alkaline phosphatase (ALP), an important enzyme in living organisms, plays significant roles in the hydrolysis of phosphate groups from nucleic acids, proteins, and other substrates. Abnormal level ...of ALP in serum is related to a variety of diseases. Low expression of ALP can cause blood diseases, such as anemia and leukemia, while over-expression of ALP can lead to disorders in liver, prostate, endocrine system, and bone tissues. Therefore, to monitor the ALP level in physiological and pathological events, it is in urgent need to develop a rapid, accurate, sensitive, and non-invasive approach, which can also be of great significance for the improvement of corresponding clinical agents. With the development of fluorescent probes, many advantages of fluorescent probes for ALP detection, such as simple operation, non-invasive, real-time imaging, economy, fast response, and so on, have been gradually highlighted. In this review, we enumerated almost all the ALP fluorescent probes from 2009 to now and summarized their respective characteristics, in order to provide a unified platform for their standardized evaluation. Meanwhile, we tried to systematically review the research progress of ALP fluorescent probes, including both small-molecule and nanoscale ones. Logically, we focused on the structures, reaction mechanisms, and biological applications of ALP fluorescent probes. In addition, the prospects of ALP in the near future have also been foreseen. We hope that this review will be helpful for the investigators who are interested in ALP-associated biological procedures, and even in the regulation of more extensive enzyme levels.
•Alkaline phosphatase (ALP) fluorescent probes possess respective characteristics.•Different combinations between fluorophores and detection mechanisms of small-molecule fluorescent probes.•ALP nano probes included noble metal nanoparticles, metal-organic frameworks, AIEgens, quantum dots, terbium chelates, etc.•ALP level was crucial for diagnosis of diseases in clinical medicine.•ALP can hydrolysis 5′-phosphate residues from nucleic acid molecules in biology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•The fluorescent probes, chemiluminescent probes and bioluminescent probes for sensing NTRs were reviewed.•The design strategies of those modes were discussed based on different probes.•The ...advantages and drawbacks of those detection modes were discussed.•A prospect for the detection of NTRs activity was proposed.
As one of the most representative hypoxic enzymes, nitroreductases (NTRs) play momentous roles in malignant tumor progression, metastasis, invasion and angiogenesis. They are also a key hallmark of highly aggressive disease in various hypoxic tumor cells. In addition, NTRs participate in essential processes of detoxification, pro-drug activation as well as radiation therapy. Thus, the detection of NTRs has great importance for theranostic and drug development. In this review, we focused on the design principles, sensing mechanisms and biological applications of small-molecule probes for NTRs detection over the past ten years (2010–2020). We also highlighted the challenges and future directions in this rapidly developing field. Significantly, we hope that some insights and inspiration for future research work will be provided to surmount the Achilles’ Heels of the small-molecule probes, such as limited application, for detecting NTRs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
4.
FAK inhibitors in Cancer, a patent review Lv, Peng-Cheng; Jiang, Ai-Qin; Zhang, Wei-Ming ...
Expert opinion on therapeutic patents,
02/2018, Volume:
28, Issue:
2
Journal Article
Peer reviewed
Introduction: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes at sites of cell adhesion to the extracellular matrix (ECM) and mediates signalling events downstream of ...integrin engagement of the ECM. FAK is known to regulate cell survival, proliferation and migration.
Areas covered: FAK expression has also been shown to be up-regulated in many cancer types. Previous study also indicates that FAK-mediated signaling and functions are intrinsically involved in the progression of tumor aggressiveness, suggesting that FAK is a promising target for anticancer therapies. Small molecule FAK inhibitors have been developed and are being tested in clinical phase trials.
Expert Opinion: These inhibitors have demonstrated to be effective by inducing tumor cell apoptosis in addition to reducing metastasis and angiogenesis. In this review, we give updates on the design, synthesis and structure-activity relationship analysis of small molecule FAK inhibitors discovered from 2015 until now. We also review the FAK inhibitors that are in clinical development and highlight the future prospects.
Background
IBM Watson for Oncology (WFO), which can use natural language processing to evaluate data in structured and unstructured formats, has begun to be used in China. It provides physicians with ...evidence‐based treatment options and ranks them in three categories for treatment decision support. This study was designed to examine the concordance between the treatment recommendation proposed by WFO and actual clinical decisions by oncologists in our cancer center, which would reflect the differences of cancer treatment between China and the U.S.
Patients and Methods
Retrospective data from 362 patients with cancer were ingested into WFO from April 2017 to October 2017. WFO recommendations were provided in three categories: recommended, for consideration, and not recommended. Concordance was analyzed by comparing the treatment decisions proposed by WFO with those of the multidisciplinary tumor board. Concordance was achieved when the oncologists' treatment decisions were in the recommended or for consideration categories in WFO.
Results
Ovarian cancer showed the highest concordance, which was 96%. Lung cancer and breast cancer obtained a concordance of slightly above 80%. The concordance of rectal cancer was 74%, whereas colon cancer and cervical cancer showed the same concordance of 64%. In particular, the concordance of gastric cancer was very low, only 12%, and 88% of cases were under physicians choice.
Conclusion
Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major cause of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. ClinicalTrials.gov Identifier: NCT03400514.
Implications for Practice
IBM Watson for Oncology (WFO) has begun to be used in China. In this study, concordance was examined between the treatment recommendation proposed by WFO and clinical decisions for 362 patients in our cancer center, which could reflect the differences of cancer treatment between China and the U.S. Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major causes of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. This study may have a significant effect on application of artificial intelligence systems in China.
摘要
背景。IBM 沃森肿瘤 (WFO) 可以使用自然语言处理程序来评估结构化和非结构化格式的数据，我们已在中国开展使用。它可以提供各种基于证据的治疗选择并将它们划分为三个类别，以提供治疗决策支持。本研究旨在检验 WFO 提出的治疗建议与我们癌症中心的肿瘤医生制定的实际临床决策之间的一致性，这可以反映出中美之间的癌症治疗差异。
患者和方法。在 2017 年 4 月至 2017 年 10 月期间，WFO 输入了来自 362 名癌症患者的回顾性数据。按照三种类别提供 WFO 建议:建议、以供考虑和不建议。通过对比 WFO 与多学科肿瘤委员会建议的治疗决策，我们对一致性进行了分析。当肿瘤医生的治疗决策在 WFO 中属于建议或以供考虑的类别时，即表示实现了一致性。
结果。卵巢癌显示出最高的一致性，为 96%。肺癌和乳腺癌取得了略高于 80% 的一致性。直肠癌的一致性为 74%，而结肠癌和宫颈癌显示出相同的一致性，同为 64%。特别值得注意的是，胃癌的一致性非常低，仅为 12%，88% 的病例均由医生选择。
结论。不同的癌症类型显示出不同的一致性，只有胃癌明显不太可能一致。发病率和药物可能是导致不一致的主要原因。为了实现在中国的全面、快速应用，WFO 需要加速本地化。ClinicalTrials.gov 标识符:NCT03400514。
对临床实践的提示:我们现已在中国开始使用 IBM 沃森肿瘤 (WFO)。在本研究中，我们检验了针对我们癌症中心的 362 名患者的 WFO 治疗建议与临床决策之间的一致性，这可以反映出中美之间的癌症治疗差异。不同的癌症类型显示出不同的一致性，只有胃癌明显不太可能一致。发病率和药物可能是导致不一致的主要原因。为了实现在中国的全面、快速应用，WFO 需要加速本地化。本研究可能对人工智能系统在中国的应用产生重大影响。
Using the updated version of IBM Watson for Oncology, this study explored the concordance of the suggested therapeutic regimen between Watson and physicians in China. This article reports results and suggests some similarities and differences between the East and West in the treatment of cancer.
A series of novel pyrazoline-containing derivatives (15–47) has been designed, synthesized and evaluated for their biological activities. Among them, compound 18 displayed the most potent ...antiproliferative activity against A549, MCF-7 and HepG-2 cells line (IC50 = 0.07 μM, 0.05 μM, 0.03 μM, respectively) and the tubulin polymerization inhibitory activity (IC50 = 1.88 μM), being comparable to CA-4. Furthermore, we also tested that compound 18 was a potent inducer of apoptosis in HepG-2 cells and it had cellular effects typical for microtubule interacting agents, causing accumulation of cells in the G2/M phase of the cell cycle. These studies, along with molecular docking, provided a new molecular scaffold for the further development of antitumor agents that target tubulin.
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•32 novel pyrazoline-containing derivatives has been designed and synthesized.•Crystal structure of compound 23 was determined.•Their biological activities were tested as potential tubulin assembling inhibitors.•The docking model were established and analyzed.•Compound 18 displayed the most potent antitumor activity.
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Hydrazine is a very important industrial chemical with high toxicity to the human body. In this work, a fluorescent probe HZ, based on the substitution-cyclization-elimination cascade which initiated ...by hydrazine, was designed and synthesized. HZ had various characteristics such as high selectivity, high sensitivity, fast detection speed, wide application range, and so on. After treating with hydrazine, the fluorescence signal of HZ at 520 nm in aqueous solution was significantly enhanced. Furthermore, HZ had the linear range of 1–10 equivalent for monitoring hydrazine, and the solution showed a colorless to yellow color change. In practical application, the detection limit of HZ for the detection of hydrazine was only 0.75 μM, which could be utilized for trace detection of hydrazine in different water samples. These indicated that HZ had a broad application prospect in the fields of environmental protection and water treatment. This work not only provided a useful instrument for the detection of the ecological environment but also supplied important information for the system optimization of other ecological environment detectors. In addition, HZ could monitor endogenous and exogenous hydrazine in MCF-7 cells successfully, which demonstrated its potential for practical application in complex biological systems.
•A novel turn-on fluorescent probe based on the benzofuranone derivatives.•Exhibiting short reaction time, high selectivity and low detection limit to hydrazine.•The probe could quantify hydrazine in different environmental water samples.•The probe could image exogenous and endogenous hydrazine in the living cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A series of 1,3,4-oxadiazole derivatives have been designed and synthesized, and their biological activities were also evaluated for FAK inhibitory activity. Compound 4 possessed the most potent ...enzyme inhibition activities (IC50=1.2±0.3μM for FAK) and anticancer activities (IC50=5.68μg/ml for MCF-7 and IC50=10.21μg/ml for HT29). Structure–activity relationship was also analysed to provide more pharmacophore understanding that could be used to design new agents with more potent FAK inhibitory activity. Docking simulation was performed to explore the binding model of compound 4 with FAK.
1,3,4-Oxadiazole derivatives have drawn continuing interest over the years because of their varied biological activities. In order to search for novel anticancer agents, we designed and synthesized a series of new 1,3,4-oxadiazole derivatives containing benzotriazole moiety as potential focal adhesion kinase (FAK) inhibitors. All the synthesized compounds were firstly reported. Among the compounds, compound 4 shows the most potent inhibitory activity against MCF-7 and HT29 cell lines with IC50 values of 5.68μg/ml and 10.21μg/ml, respectively. Besides, all the compounds were assayed for FAK inhibitory activity using the TRAP–PCR–ELISA assay. The results showed compound 4 exhibited the most potent FAK inhibitory activity with IC50 values of 1.2±0.3μM. Docking simulation by positioning compound 4 into the FAK structure active site was performed to explore the possible binding mode. Apoptosis which was analyzed by flow cytometry, demonstrated that compound 4 induced apoptosis against MCF-7 cells. Therefore, compound 4 may be a potential anticancer agent against MCF-7 cancer cell.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background and Importance
Cervical spinal cord hemangioblastoma with intracystic hemorrhage is a rare entity and presents a challenge for clinicians with regard to its timely diagnosis and ...appropriate treatment.
Case Presentation
A 35-year-old man presented with sudden-onset acute and progressive neck pain and severe radicular pain in his left upper limb. Motor weakness and numbness in the left upper and lower limbs with gait ataxia followed 2 days later. His initial diagnosis was acute myelitis, and he was treated with glucocorticoids for 2 weeks. Follow-up contrast-enhanced magnetic resonance imaging (MRI) suggested a spinal cystic hemangioblastoma with intracystic hemorrhage at the C3-4 level. The tumor was totally removed by minimally invasive unilateral hemi-semi-laminectomy via a posterior transcystic approach. The postoperative course was uneventful, and postoperative MRI revealed no residual tumor. The patient showed full neurological recovery at the 1.5-year follow-up, and computed tomography with a volume-rendering technique showed regrowth of the left C3 lamina.
Conclusion
Close MRI follow-up and thin-section imaging are invaluable for the timely diagnosis of spinal hemangioblastoma with intracystic hemorrhage, which was safely removed via minimally invasive microsurgery in the present case.
A series of novel 1,3,4-thiadiazol-2-amide derivatives containing different substituent groups have been designed, synthesized and evaluated for the inhibitory activity against tubulin polymerization ...and cancer cell inhibitory activity. Docking simulation and 3D-QSAR study were conducted.
A series of 1,3,4-thiadiazol-2-amide derivatives (6a–w) were designed and synthesized as potential inhibitors of tubulin polymerization and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 6f exhibited the most potent anticancer activity against A549, MCF-7 and HepG2 cancer cell lines with IC50 values of 0.03μM, 0.06μM and 0.05μM, respectively. Compound 6f also exhibited significant tubulin polymerization inhibitory activity (IC50=1.73μM), which was superior to the positive control. The obtained results, along with a 3D-QSAR study and molecular docking that were used for investigating the probable binding mode, could provide an important basis for further optimization of compound 6f as a novel anticancer agent.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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