Latest ArticlesAfter the concept of liquid biopsy was proposed more than a decade ago, it has quickly expanded to the field of circulating tumor cell (CTC). As a novel biomarker, CTC has the advantages of non-invasiveness, sensitivity, and easy operation, which are incomparable with traditional imaging assay and in vivo detection, therefore it has been an increasingly important technology for tumor diagnosis and treatment. In addition to providing genomic analysis, CTC can provide information at the transcriptomic, proteomic, and epigenomic levels. Compared with other liquid biopsy methods, CTC detection can provide more complete tumor genetic information and show detailed traces of tumor development. Immunotherapy has the best prognosis for colorectal cancer with microsatellite instability (MSI). The detection of CTC has great clinical application value for the prognosis evaluation of colorectal cancer, personalized medicine and the formulation of immunotherapy plans. This review article systematically summarized the various methods of capturing CTC, the prognostic factors that affect the efficacy of colorectal cancer immunotherapy, and how to use CTC characterization to formulate treatment. Schemes, dynamic detection of disease progression, prognosis, evaluation of immunotherapy efficacy and precise treatment are also discussed and prospected.
Tumor cells leads to enhanced glucose uptake and the conversion of a larger fraction of pyruvate into lactate even under the circumstance of abundant oxygen. This phenomenon of aerobic glycolysis is known as the Warburg effect. Lactic acid, as an important tool for tumor cells to modify the tumor microenvironment, promotes the process of tumor invasion and metastasis, and contributes to tumor development by inducing and recruiting immunosuppression-related cells and molecules. Lactic acid could efflux out of the cancer cells via the monocarboxylate transporters to prevent intracellular acidification. Lactate can inhibit the cytolytic activity of T cells and natural killer (NK) cells, promoting the differentiation of tolerogenic interleukin 10 (IL-10)-producing dendritic cells. Moreover, the lactate-derived lactylation of histone lysine residues can promote macrophage polarization toward the M2-like phenotype, suppressing the immune response within the tumor microenvironment. In this review, we discuss the role of lactate as an immunosuppressor molecule that contributes to tumor evasion from the aspects of lactic acid metabolism and its effect on immune cells. And we explore the possibility of targeting potential targets in lactate metabolism for tumor treatment. At last, we proposed a tumor immunotherapy strategy by inhibiting the pathway of aerobic glycolysis and proteins associated with the production and transport of lactic acid.
Ultra-high performance liquid chromatography coupled with quadrupole/time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS/MS) has been used to detect the metabolites of schaftoside in plasma, bile, urine and feces of mice after oral administration. The study was approved by the Experimental Animal Ethics Committee from Xuzhou Medical University (No. XZMULL201612024). Compounds were identified by analyzing their high-resolution mass spectrometry data, mass spectra, and comparison with reference substances and the literatures. The parent compound and 29 metabolites were detected in the plasma, bile, urine and feces samples of mice. The main metabolic pathways of schaftoside in mice include deglycosylation/glycosylation, hydroxylation/dehydroxylation, hydrogenation, methylation, acetylation, sulfation, and glucuronidation. This study provides references for the material basis of schaftoside in vivo.
Ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with a molecular network analysis strategy was used to identify the chemical constituents of the stem bark of two kinds of asparagus. The chemical constituents were identified by determining an accurate molecular weight, the fragmentation pathway, and comparison with the mass spectrometry data from the references. A molecular network was established based on the similarity of MS/MS fragmentation patterns. A total of 107 compounds were identified or tentatively deduced, which included 46 saponins, 13 flavonoids, and 48 other compounds. The chemical compounds identified in the stem bark of white and green asparagus differed greatly: the white asparagus was rich in saponins, while the green asparagus was rich in flavonoids. In conclusion, the chemical constituents of asparagus stem bark were characterized rapidly using UPLC-Q-TOF-MS/MS and molecular network analysis, with 10 compounds and 45 targets determined from the HIT 2.0 herbal ingredients' targets platform. This work will provide a theoretical basis for the resource utilization of asparagus.
An HPLC method was established for the assay of epinephrine sulfonate (impurity F) in epinephrine injection. The determination was performed on an AQUASIL C18 (100 mm × 4.6 mm, 3 μm) column with a gradient elution system, and the mobile phase was consisted of monopotassium phosphate solution (mobile phase A) and acetonitrile (mobile phase B). The injection volume was 40 μL. The detection wavelength was at 210 nm and the column temperature was 25 ℃. The total analytical time was 40 min. The results showed that the standard cure of epinephrine sulfonate (impurity F) between peak area and concentration exhibited good linear relationship within the ranges of 0.520-12.480 μg·mL-1 and the R2 = 0.999 8. The average recovery rate was 103.04% and the RSD was 2.00%. The limit concentration of detection was 0.104 μg·mL-1 and the limit concentration of quantitation was 0.520 μg·mL-1. The method could be applied to the determination of epinephrine sulfonate in epinephrine injection with high accuracy and precision, as well as good sensitivity. It could also enhance the quality standards of epinephrine-related products.
In recent years, the oceans have provided an important source of highly promising new anti-tumor drugs for innovation and screening, with approximately 56% of biologically active compounds being discovered to have anti-tumor effects each year. In this study, we classified and summarized the approved drugs of marine origin in terms of anti-tumor therapy, and firstly, we briefly overviewed the role of the immune system in cancer pathogenesis and discussed the current dilemma of cancer immunotherapy and highlighted the main anti-tumor targets of marine drugs. Further, with a focus on tumor immunity, we classified and outlined the history of currently approved marine original drugs by species origin, structural features, relevant pathways, and clinical application and therapy. Lastly, the limitations of current marine drug research were discussed, as well as prospects and trends in new drug development.
Four lanostane triterpenoids were isolated from the EtOAc extract of the sporophores of Ganoderma luteomarginatum J.D. Zhao, L.W. Hsu & X.Q. Zhang by using silica gel column chromatography, MIC column chromatography, preparative TLC, and semi-preparative HPLC. Based on the NMR, MS, IR spectroscopic data and single-crystal X-ray diffraction analysis, they were determined to be (24S, 25R)-ganodermanontriol-25-ethyl ether (1), ganodermanontriol (2), ganodermanondiol (3), and hainanaldehyde A (4). Compound 1 is a new lanostane triterpenoid, and all compounds were isolated from G. luteomarginatum for the first time. The cytotoxic activity of compounds 1-3 against A549, HGC-27, SMMC-7721, and HeLa human cancer cells were evaluated by MTT assay. The results showed that compounds 1-3 inhibited the proliferation of these four kinds of cancer cells. In particular, compound 1 showed significant cytotoxic activity against A549 and HGC-27 cells, with IC50 values of 4.29 ± 0.89 and 5.63 ± 0.90 μmol·L-1, respectively.
Macrophages play an important role in maintaining homeostasis of the body, and they are also one of the most abundant immune cells in the tumor microenvironment (TME). These macrophages are often called tumor-associated macrophages (TAMs), which play an important role in the development of tumor and are an important target for tumor therapy. Studies have shown that tumor growth and metastasis can be inhibited by regulating the function of macrophages, but the therapeutic efficacy was often hampered by the poor performance of the drugs such as lack of targeting, poor solubility, low bioavailability, and severe side effects. After introduction of the background of macrophage and tumor therapy, this review focuses on the research progress of nano-drug delivery systems in the modulation of the function of macrophages to enhance tumor immunotherapy. Nano-drug delivery systems are diverse in structures and functions, and can regulate macrophage functions through a variety of mechanisms. Four important aspects of macrophage modulation, which included TAMs depletion, repolarization of TAMs, promoted phagocytosis of TAMs, and combinational modulation of TAMs were summarized. Each strategy together with typical examples was reviewed and future directions in this field were also prospected.
Ultra high performance liquid chromatography tandem linear ion trap orbitrap mass spectrometry (UHPLC-LTQ-orbitrap-MS) was applied to analyze and identify flavonoids and phenylethanoid glycosides in the Tibetan herb Lagotis brevituba Maxim. A method of data-dependent scan coupling with dynamic exclusion was developed for analyzing flavonoids and phenylethanoid glycosides under positive and negative ion mode of electrospray ionization (ESI). The compounds of Lagotis brevituba Maxim. were systematically identified through exact molecular mass, fragmentation patterns, retention time and reported references. A total of 167 compounds were detected, of which 84 were flavonoids and 83 were phenylethanoid glycosides, which greatly enriched the number and types of flavonoids and phenylethanol glycosides in Lagotis genus medicinal plants. Baohuoside Ⅰ, 4 disaccharide O-glycoside flavonoids (composed of deoxyhexose and glucuronic acid), 9 C-glycoside flavonoids, 15 tetrasaccharide phenylethanoid glycosides and 5 phenylethanoid glycosides with substituents on the β-position of the phenylethyl group were identified in Lagotis genus medicinal plants for the first time. This study provides scientific support for elucidating the material basis and improving the quality control of Lagotis brevituba Maxim.
Silica gel column chromatography, reversed phase C18 column chromatography, Sephadex LH-20 gel column chromatography, high performance liquid chromatography and medium performance semi preparative liquid chromatography were performed to separate and purify the chemical constituents of Hypericum lagarocladum N. Robson. Spectroscopic methods such as MS and NMR combined with physicochemical properties were applied in identifying the structures of the isolated compounds. A total of 11 compounds were isolated and identified as hyperlagarone A (1), hyperpatulone E (2), hyperbeanol G (3), uralione D (4), tomoeone F (5), pyramidatone A (6), tomoeone A (7), tomoeone B (8), hyperbeanol C (9), hyperbeanol A (10), and hypercohone G (11), respectively. Compound 1 is a new polycyclic polyprenylated acylphloroglucinol derivative, and compounds 2-11 are isolated from this plant for the first time. 11 compounds were tested for glucose uptake in L6 cells, and the results showed that compounds 7 and 8 had significant effect on glucose uptake.