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Globo H (GH) is a hexasaccharide specifically overexpressed on a variety of cancer cells and therefore, a good candidate for cancer vaccine development. To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked GH to a carrier protein, including keyhole limpet hemocyanion, diphtheria toxoid cross-reactive material (CRM) 197 (DT), tetanus toxoid, and BSA, and combined with an adjuvant, and it was administered to mice for the study of immune response. Glycan microarray analysis of the antiserum obtained indicated that the combination of GH-DT adjuvanted with the α-galactosylceramide C34 has the highest enhancement of anti-GH IgG. Compared with the phase III clinical trial vaccine, GH–keyhole limpet hemocyanion/QS21, the GH-DT/C34 vaccine elicited more IgG antibodies, which are more selective for GH and the GH-related epitopes, stage-specific embryonic antigen 3 (SSEA3) and SSEA4, all of which were specifically overexpressed on breast cancer cells and breast cancer stem cells with SSEA4 at the highest level (>90%). We, therefore, further developed SSEA4-DT/C34 as a vaccine candidate, and after immunization, it was found that the elicited antibodies are also IgG-dominant and very specific for SSEA4.

Antibodies have been developed as therapeutic agents for the treatment of cancer, infection, and inflammation. In addition to binding activity toward the target, antibodies also exhibit effector-mediated activities through the interaction of the Fc glycan and the Fc receptors on immune cells. To identify the optimal glycan structures for individual antibodies with desired activity, we have developed an effective method to modify the Fc-glycan structures to a homogeneous glycoform. In this study, it was found that the biantennary N-glycan structure with two terminal alpha-2,6-linked sialic acids is a common and optimized structure for the enhancement of antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antiinflammatory activities.

NRF2, a redox sensitive transcription factor, is up-regulated in head and neck squamous cell carcinoma (HNSCC), however, the associated impact and regulatory mechanisms remain unclear. The protein expression of NRF2 in HNSCC specimens was examined by IHC. The regulatory effect of c-MYC on NRF2 was validated by ChIP-qPCR, RT-qPCR and western blot. The impacts of NRF2 on malignant progression of HNSCC were determined through genetic manipulation and pharmacological inhibition and . The gene-set enrichment analysis (GSEA) on expression data of cDNA microarray combined with ChIP-qPCR, RT-qPCR, western blot, transwell migration/ invasion, cell proliferation and soft agar colony formation assays were used to investigate the regulatory mechanisms of NRF2. NRF2 expression is positively correlated with malignant features of HNSCC. In addition, carcinogens, such as nicotine and arecoline, trigger c-MYC-directed NRF2 activation in HNSCC cells. NRF2 reprograms a wide range of cancer metabolic pathways and the most notable is the pentose phosphate pathway (PPP). Furthermore, glucose-6-phosphate dehydrogenase (G6PD) and transketolase (TKT) are critical downstream effectors of NRF2 that drive malignant progression of HNSCC; the coherently expressed signature NRF2/G6PD/TKT gene set is a potential prognostic biomarker for prediction of patient overall survival. Notably, G6PD- and TKT-regulated nucleotide biosynthesis is more important than redox regulation in determining malignant progression of HNSCC. Carcinogens trigger c-MYC-directed NRF2 activation. Over-activation of NRF2 promotes malignant progression of HNSCC through reprogramming G6PD- and TKT-mediated nucleotide biosynthesis. Targeting NRF2-directed cellular metabolism is an effective strategy for development of novel treatments for head and neck cancer.

Defective arginine synthesis, due to the silencing of argininosuccinate synthase 1 (ASS1), is a common metabolic vulnerability in cancer, known as arginine auxotrophy. Understanding how arginine depletion kills arginine-auxotrophic cancer cells will facilitate the development of anti-cancer therapeutic strategies. Here we show that depletion of extracellular arginine in arginine-auxotrophic cancer cells causes mitochondrial distress and transcriptional reprogramming. Mechanistically, arginine starvation induces asparagine synthetase (ASNS), depleting these cancer cells of aspartate, and disrupting their malate-aspartate shuttle. Supplementation of aspartate, depletion of mitochondria, and knockdown of ASNS all protect the arginine-starved cells, establishing the causal effects of aspartate depletion and mitochondrial dysfunction on the arginine starvation-induced cell death. Furthermore, dietary arginine restriction reduced tumor growth in a xenograft model of ASS1-deficient breast cancer. Our data challenge the view that ASNS promotes homeostasis, arguing instead that ASNS-induced aspartate depletion promotes cytotoxicity, which can be exploited for anti-cancer therapies. Chun-Ting Cheng et al. demonstrate that arginine starvation kills arginine-auxotrophic cancer cells by depleting them of aspartate through asparagine synthetase (ASNS) and disrupting their mitochondrial metabolism. This study presents ASNS-induced aspartate depletion as an anti-cancer therapeutic strategy.

Pinus taiwanensis Hayata (Pinaceae) is an endemic plant in Taiwan. According to the Chinese Materia Medica Grand Dictionary, the Pinus species is mainly used to relieve pain, and eliminate pus and toxicity. In this study, nineteen compounds were isolated from the ethyl acetate layer of the ethanolic extract of P. taiwanensis Hayata twigs using bioassay-guided fractionation, and their anti-melanoma effects were investigated through a B16-F10 mouse melanoma cell model. The structures of the purified compounds were identified by 2D-NMR, MS, and IR, including 1 triterpenoid, 9 diterpenoids, 2 lignans, 4 phenolics, 1 phenylpropanoid, 1 flavonoid, and 1 steroid. Among them, compound 3 was found to be a new diterpene. Some of the compounds (2, 5, 6, 17, 18) showed moderate cytotoxicity effects. On the other hand, the anti-melanoma effect was no better than that from the original ethyl acetate layer. We presumed it resulted from the synergistic effect, although further experimentation needs to be performed.

Background Kidney function is associated with clinical outcomes in patients with cancer. Objectives This study aimed to assess the association between kidney function decline and cancer‐related mortality among community‐dwelling elderly individuals. Design This was a retrospective longitudinal cohort study. Participants The 61,988 participants were from an elderly health examination database in Taipei City from 2005 to 2012. Measurements Multivariable logistic regression was used to assess the association between baseline covariates and rapidly deteriorating estimated glomerular filtration rate (eGFR). In addition, Cox proportional hazards model and the Fine–Gray model were used to quantify the effects of covariates on total cancer mortality and six specific cancer mortalities. Results During the follow‐up period, 1482 participants died of cancer. Their baseline average eGFR was 73.8 ± 19.9 mL/min/1.73 m2, and 18.3% had rapid renal function decline (≥5 mL/min/1.73 m2 per year). Rapid renal function decline was positively related to age, baseline eGFR, proteinuria, hypertension, waist circumferences, high log triglyceride levels, and diabetes mellitus (DM) history. In Cox proportional hazard models, participants with rapid eGFR decline had an increased risk of cancer mortality [hazard ratio (95% CI): 1.97 (1.73, 2.24); p < 0.001] compared to those without rapid eGFR decline. In the analysis of site‐specific cancer mortality risk, rapid eGFR decline was associated with six site‐specific cancer mortality, namely gastrointestinal tract, hepatobiliary, lung, prostate, urinary tract, and hematological malignancies. Conclusions Elderly individuals with rapid kidney function decline had higher cancer mortality risks. Serial assessments of dynamic changes in eGFR might provide information relevant for cancer prognosis. This study aimed to assess the association between kidney function decline and cancer‐related mortality among community‐dwelling elderly individuals. In Cox proportional hazard models, participants with rapid eGFR decline had an increased risk of cancer mortality compared to those without rapid eGFR decline. In the analysis of site‐specific cancer mortality risk, rapid eGFR decline was associated with six site‐specific cancer mortality, namely gastrointestinal tract, hepatobiliary, lung, prostate, urinary tract, and hematological malignancies.

In previous research, we found α-enolase to be inversely correlated with progression-free and overall survival in lung cancer patients and detected α-enolase on the surface of lung cancer cells. Based on these findings, we hypothesized that surface α-enolase has a significant role in cancer metastasis and tested this hypothesis in the current study. We found that α-enolase was co-immunoprecipitated with urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and plasminogen in lung cancer cells and interacted with these proteins in a cell-free dot blotting assay, which can be interrupted by α-enolase-specific antibody. α-Enolase in lung cancer cells co-localized with these proteins and was present at the site of pericellular degradation of extracellular matrix components. Treatment with antibody against α-enolase in vitro suppressed cell-associated plasminogen and matrix metalloproteinase activation, collagen and gelatin degradation, and cell invasion. Examination of the effect of treatment with shRNA plasmids revealed that down regulation of α-enolase decreases extracellular matrix degradation by and the invasion capacity of lung cancer cells. Adoptive transfer of α-enolase-specific antibody to mice resulted in accumulation of antibody in subcutaneous tumor and inhibited the formation of tumor metastasis in lung and bone. This study demonstrated that surface α-enolase promotes extracellular matrix degradation and invasion of cancer cells and that targeting surface α-enolase is a promising approach to suppress tumor metastasis.

The rhizoma of Ligusticum sinense, a Chinese medicinal plant, has long been used as a cosmetic for the whitening and hydrating of the skin in ancient China. In order to investigate the antimelanogenic components of the rhizoma of L. sinense, we performed an antimelanogenesis assay-guided purification using semi-preparative HPLC accompanied with spectroscopic analysis to determine the active components. Based on the bioassay-guided method, 24 compounds were isolated and identified from the ethyl acetate layer of methanolic extracts of L. sinense, and among these, 5-[3-(4-hydroxy-3-methoxyphenyl)allyl]ferulic acid (1) and cis-4-pentylcyclohex-3-ene-1,2-diol (2) were new compounds. All the pure isolates were subjected to antimelanogenesis assay using murine melanoma B16-F10 cells. Compound 1 and (3S,3aR)-neocnidilide (8) exhibited antimelanogenesis activities with IC50 values of 78.9 and 31.1 μM, respectively, without obvious cytotoxicity. Further investigation showed that compound 8 demonstrated significant anti-pigmentation activity on zebrafish embryos (10‒20 μM) compared to arbutin (20 μM), and without any cytotoxicity against normal human epidermal keratinocytes. These findings suggest that (3S,3aR)-neocnidilide (8) is a potent antimelanogenic and non-cytotoxic natural compound and may be developed potentially as a skin-whitening agent for cosmetic uses.

Coffea arabica extract (CAE) containing 48.3 ± 0.4 mg/g of chlorogenic acid and a trace amount of caffeic acid was found to alleviate photoaging activity in human skin fibroblasts. In this study, polyphenol-rich CAE was investigated for its antioxidant and antiinflammatory properties, as well as for its capability to alleviate ultraviolet B (UVB)-induced photodamage in BALB/c hairless mice. The results indicated that 500 μg/mL of CAE exhibited a reducing power of 94.7%, ferrous ion chelating activity of 46.4%, and hydroxyl radical scavenging activity of 20.3%. The CAE dose dependently reduced UVB-induced reactive oxygen species (ROS) generation in fibroblasts. Furthermore, CAE inhibited the UVB-induced expression of cyclooxygenase-2 and p-inhibitor κB, and the translocation of nuclear factor-kappa B (NF-κB) to the nucleus of fibroblasts. In addition, CAE alleviated UVB-induced photoaging and photodamage in BALB/c hairless mice by restoring the collagen content and reduced UVB-induced epidermal hyperplasia. CAE also inhibited UVB-induced NF-κB, interleukin-6, and matrix metalloproteinase-1 expression in the hairless mouse skin. The results indicated that CAE exhibits antiphotodamage activity by inhibiting UV-induced oxidative stress and inflammation. Therefore, CAE is a candidate for use in antioxidant, antiinflammatory, and antiphotodamage products.

Background Dolichandrone spathacea ( D. spathacea ) is a traditional medicine used to treat chronic bronchitis (CB) in Vietnam and India. However, phytochemicals and potential mechanisms of this species against CB have not been fully illuminated. Therefore, this study aimed to isolate and elucidate the phytochemicals of D. spathacea , clarify its potential molecular mechanisms and key therapeutic targets in treating CB through network pharmacology and validate these findings using molecular docking, and experimental approaches. Results Three compounds, beta-sitosterol, 6-O- trans - p- coumaroyl ajugol, 6- O -[( E )-4-methoxycinnamoyl] catalpol were isolated from the EtOAc fraction, with beta-sitosterol being reported for the first time of this species. After combining the phytochemicals of this species identified in this study with those reported in the literature references, 59 compounds were obtained, and 30 bioactive compounds were screened. Among these, luteolin was predicted to interact with the highest number of CB-related proteins. Using the GeneCards and DrugBank databases, 66 intersecting target genes were identified between D. spathacea and CB. The protein–protein interaction analysis identified core targets, including TNF, AKT1, SRC, EGFR, IL2, MMP-9, HSP90AA1, and PTGS2. The KEGG enrichment analyses suggested that this species exerts its therapeutic effects on CB by modulating various biological processes and pathways . Notably, the top three target genes—PTGS2, TNF, and MMP-9—were enriched in the TNF and IL-17 signaling pathways. The computational docking suggested that PTGS2, TNF, and MMP-9 could bind to all key bioactive compounds of D. spathacea . The experimental validation revealed that ethanol extract inhibited nitric oxide production induced by LPS, with an IC 50 value of 25.34 μg/mL. At the concentration of 100 μg/mL, the ethanol extract effectively inhibited the production of TNF-α, IL-1β cytokine, with inhibition rates of 71.67%, and 90.22%, respectively. Conclusion This study systematically investigated the phytoconstituents, core target genes, and key mechanisms of D. spathacea in the treatment of chronic bronchitis. It highlights the role of this species in modulating the TNF and IL-17 signaling pathways in CB therapy. The findings suggest that D. spathacea exhibits significant anti-inflammatory effects on CB, providing robust scientific evidence and novel insights for further research on chronic bronchitis.