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Blueberry is the source of a variety of bioactive substances, including phenolic compounds, such as anthocyanins, pterostilbene, phenolic acids, etc. Several studies have revealed that polyphenols in blueberry have important bioactivities in maintaining health, such as antioxidant and anti-tumor activities, immune regulation, the prevention of chronic diseases, etc. Therefore, these phenolic compounds in blueberries have been widely used in the field of healthcare, and the extraction, isolation, and purification of phenolic compounds are the prerequisites for their utilization. It is imperative to systematically review the research progress and prospects of phenolic compounds present in blueberries. Herein, the latest progress in the extraction, purification, and analysis of phenolic compounds from blueberries is reviewed, which can in turn provide a foundation for further research and usage of blueberries. [ABSTRACT FROM AUTHOR]

In this issue of Structure , Mabanglo et al. characterize five ClpP agonists termed TRs. The co-crystal structures reveal more robust shape and charge complementarities than the anti-cancer agent ONC201. These novel compounds are of potential therapeutic interest because they enhance ClpP proteolytic activity and have an inhibitory effect on tumor cell growth. [ABSTRACT FROM AUTHOR]

In recent decades, digestive system tumors (DST) have become the primary cause of cancer-related deaths worldwide. Improving tumor prognosis and drug response prediction holds significant importance in personalized medicine. In order to construct an effective and interpretable model that integrates multiple omics data, the Multi-omics Fusion Graph Attention Network (MFGAN) is proposed for survival prediction and drug response prediction in DST. In this method, the similarity matrix of each kind of omics data is calculated and a new graph structure is learned by Graph Transformer (GT). Next, to learn the features of every kind of omics data from the TCGA and GDSC databases, the Graph Attention Network (GAN) is used. Lastly, the View Correlation Discovery Network (VCDN) combines different types of omics data features to predict survival risk and drug response. Among them, the survival prediction results showed an improvement of up to 9% relative to other methods in terms of the c-index metric, with a minimum improvement of 2.6%. In terms of drug response prediction performance, there was an improvement of 4%. The ablation experiment demonstrates MFGAN's feature integration capability, and the functional enrichment analysis for significant genes explains the functional characteristics of the model. Furthermore, the prediction of unknown tumor drug response demonstrates the model's prediction ability. The proposed high-prediction comprehensive model could have important potential value for the personalized medicine of DST. • Proposing a multi-omics fusion model for survival and drug response prediction in digestive system tumors. • GT learns new graph structures, and VCDN explores the correlation of GAN-learned multi-omics features. • Experiments verified the efficacy of the proposed multi-omics integration method in survival and drug response prediction. [ABSTRACT FROM AUTHOR]

Sesame (Sesamum indicum L.) seeds are popular nutritional food but with limited knowledge about their antioxidant and antiproliferative activities of various varieties. Phytochemical profiles and antioxidant and antiproliferative activities of six varieties of sesame (Sesamum indicum L.) seeds were studied. Fenheizhi3 (black) cultivar exhibited the maximum contents of total phenolics and lignans and values of total oxygen radical absorbance capacity (ORAC) and antiproliferative activity (EC50) against HepG2 cells. Bound ORAC values showed strong associations with bound phenolics contents (r=0.976, p<0.01); in bound phenolic extracts, EC50 values showed strong negative associations with phenolic contents (r=-0.869, p<0.05) and ORAC values (r=-0.918, p<0.01). Moreover, the contents of free phenolics were higher than that of the bound phenolics, and the three black sesame seeds generally depicted higher total phenolics compared to the three white varieties. The antioxidant (ORAC values) and antiproliferation activities of six sesame seeds were both associated with contents of bound phenolics (r>0.8, p<0.05). Interestingly, nonlignan components in bound phenolics contributed to the antioxidant and antiproliferative activities. This study suggested that Fenheizhi3 variety is superior to the other five varieties as antioxidant supplements. [ABSTRACT FROM AUTHOR]

In this manuscript, a photosensitive anti-cancer drug, hypocrellin A (HA), and TiO 2 nanoparticles were co-loaded on the surface of graphene oxide (GO) as a photosensitive drug delivery system. In vitro studies have demonstrated the active uptake of the system into the mitochondrial of tumor cells. Such system has mutual sensitization mechanism to greatly improve the reactive oxygen species (ROSs) generation ability of the complex by visible light irradiation and, thereby, the strong photodynamic therapy (PDT) efficacy. Furthermore, during such PDT process, GO can be destroyed by the ROSs, which would helpful for the metabolism of this drug delivery system. [ABSTRACT FROM AUTHOR]

Highlights: [•] Combination therapy of chemotherapy and photodynamic therapy was evaluated. [•] Hypocrellin A and 7-ethyl-10-hydroxycamptothecin were co-loaded on graphene oxide. [•] The complex was formed through noncovalent π–π stacking and hydrogen bond. [•] Combination therapy exhibited a synergistic anticancer effect to cancer cell. [ABSTRACT FROM AUTHOR]

Many anticancer drugs have the capability to form stable complex with metal ions. Based on such property, a simple method to combine these drugs with transferrin, through the interaction between drug and Fe ion of transferrin, to improve their anticancer activity, is proposed. To demonstrate this technique, the complex of photosensitive anticancer drug hypocrellin A and transferrin was prepared by such facile method. The results indicated that the complex of hypocrellin A and transferrin can stabilize in aqueous solution. In vitro studies have demonstrated the superior cancer cell uptake ability of hypocrellin A-transferrin complex to the free hypocrellin A. Significant damage to such drug-impregnated tumor cells was observed upon irradiation and the cancer cells killing ability of hypocrellin A-transferrin was stronger than the free hypocrellin A within a certain range of concentrations. The above results demonstrated the validity and potential of our proposed strategy to prepare the drug delivery system of this type of anti-cancer drugs and transferrin. [ABSTRACT FROM AUTHOR]

Abstract: Polysaccharides were extracted from Jisongrong mushroom. Jisongrong polysaccharides was a water-soluble compound. Its molecular weight was about 7.4×104 Da. HPLC analysis showed that this polysaccharides was composed of mannose, ribose, rhamnose, glucose, xylose, galactose and arabinose in the molar contents of 3.3, 17.3, 6.0, 12.4, 98.4 and 2.1μM, respectively. In the range of 2800–3500cm−1, peaks at 2958 and 3407cm−1 belonging to –C–H of –CH2 groups, were observed in polysaccharides. When Jisongrong polysaccharides were orally administrated to rats for 2 months, level of lipid peroxidation products and activities of antioxidant enzymes in the blood were significantly decreased and enhanced compared to control rats. Moreover, Jisongrong polysaccharides still markedly inhibited cancer cells proliferation. These results suggested that Jisongrong polysaccharides possess a strong antioxidant and antitumour activities. [Copyright &y& Elsevier]

Abstract: We report a facile silica nanovehicle preparation procedure for hydrophobic drug delivery, which is carried out in water without adding any surfactant and additional catalyst. This strategy includes hydrophobic drug nanopaticle preparation by reprecipitation method and in situ hydrolyzation and polymerization to encapsulate this naoparticle using only N-(β-amimoethyl)-γ-aminopropyltyiethoxysilane (AETPS). To demonstrate this technique hypocrellin A (HA), a hydrophobic photosensitizing anticancer drug, is embedded into silica nanovehicle using this simple method. The resulting HA encapsulated nanovehicles (HANV) are monodisperse and stable in aqueous solution. Comparative studies with free HA and entrapped HA have demonstrated that the encapsulation effect on the embedded photosensitizer nanoparticle significantly enhances the efficacy of singlet oxygen generation and, thereby, the in vitro photodynamic efficacy. [Copyright &y& Elsevier]

Abstract: An amorphous formulation of hypocrellin A for photodynamic therapy is reported which can provide stable aqueous dispersion of such hydrophobic photosensitizers. In vitro studies have demonstrated the active uptake of amorphous formulation of hypocrellin A into the mitochondria of tumor cells. Compared with Tween-80 micelle embedded hypocrellin A, low dark-toxicity but similar light-toxicity of the amorphous one to drug impregnated tumor cells was observed. Thus, the potential of using amorphous formulation of hypocrellin A as drug delivery system for photodynamic therapy has been demonstrated. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer is an aggressive malignancy with a poor prognosis. Nanosecond pulsed electric field is a new method for local tumor ablation. However, the mechanism of nanosecond pulsed electric field therapy for triple-negative breast cancer is not clear. We constructed a mouse model of triple-negative breast cancer. Transcriptome sequencing and other techniques were used. We demonstrated that nanosecond pulsed electric field effectively ablated tumor and induced apoptosis related pathways. Nanosecond pulsed electric field ablation activated tumor immunity and promoted the infiltration of CD8+ T cells. The inhibition of residual cancer growth mediated by nanosecond pulsed electric field ablation was dependent on CXCL9 axis. Triple-negative breast cancer (TNBC) is a refractory tumor, and therapeutic options are very limited. Local ablation has been applied recently. Chemokines play a critical role in the recruitment of immune cells into ablative tumors. Nanosecond pulsed electric field (nsPEF) shows potential anti-tumor efficacy, but the mechanism for maintaining the immune effect is not very clear. Here, we applied nsPEF for treating 4T1 breast cancer cells in vitro. RNA sequencing (RNA-seq) was applied. Anti-CXCL9 was used alone or combined with nsPEF to treat triple-negative breast cancer in mice. We demonstrated that nsPEF effectively induced cell apoptosis and inhibited the growth and metastasis of triple-negative breast cancer. An immune effect, especially chemotaxis, was activated by nsPEF. The number of infiltrated CD8+ T cells was increased significantly. We found that the inhibition of residual breast cancer growth by nsPEF was dependent on the CXCL9 axis. In conclusion, our work demonstrated that nsPEF effectively ablated the tumor, aroused an immune response, and inhibited residual breast cancer growth via CXCL9 axis dependence in mice. [ABSTRACT FROM AUTHOR]

Abstract: Polyamines are naturally occurring compounds that play important roles in multiple cell processes. In most cases, phthalocyanine-polyamine (Pc-polyamine) conjugates have good anticancer activity. However, low solubility in water limits their application in photodynamic therapy (PDT). The common method to solve this problem is quaternizing the nitrogen atoms to obtain cationic derivatives. An alternative strategy by preparing hydrochloride is easily neglected. In this paper, a Pc-polyamine conjugate substituted with 1,2-diethylamino (ZnPc1) was conferred water solubility by two different strategies, which are preparing hydrochloride (ZnPc2) and quaternizing the nitrogen atoms (ZnPc3). The synthetic methods and properties of the two derivatives were compared and discussed. Results indicated that both ZnPc2 and ZnPc3 possessed good solubility in water. However, strategy of preparing hydrochloride is much easier than quaternization process and the singlet oxygen generation ability, the photostability and anticancer activity of ZnPc2 in vitro were also superior to the ZnPc3. [Copyright &y& Elsevier]

Abstract: FOXO3a, a well-known transcriptional regulator, controls a wide spectrum of biological processes. The Phosphoinositide-3-kinase (PI3K)/Akt signaling pathway inactivates FOXO3a via phosphorylation-induced nuclear exclusion and degradation. A loss or gain of FOXO3a activity has been correlated with efficiency of chemotherapies in various cancers including oral squamous cell carcinoma (OSCC). Therefore, in the current study, we have investigated the FOXO3a activity modulating and antitumor effects of rapamycin and cisplatin in OSCC cells. Cisplatin inhibited proliferation and induced apoptosis in a dose-dependent way in OSCC Tca8113 cells. Rapamycin alone had no effect on cell proliferation and apoptosis. Rapamycin downregulated the expression of S-phase kinase associated protein-2 (Skp2) and increased the FOXO3a protein stability but induced the upregulation of feedback Akt activation-mediated FOXO3a phosphorylation. Cisplatin decreased the phosphorylation of FOXO3a via Akt inhibition. Rapamycin combined with cisplatin as its feedback Akt activation inhibitor revealed the most dramatic FOXO3a nuclear localization and reactivation with the prevention of its feedback loop and exposed significant synergistic effects of decreased cell proliferation and increased apoptosis in vitro and decreased tumor size in vivo. Furthermore, the downstream effects of FOXO3a reactivation were found to be accumulation of p27 and Bim. In conclusion, rapamycin/cisplatin combination therapy boosts synergistic antitumor effects through the significant FOXO3a reactivation in OSCC cells. These results may represent a novel mechanism by which rapamycin/cisplatin combination therapy proves to be a potent molecular-targeted strategy for OSCC. [ABSTRACT FROM AUTHOR]

Eight new C21 steroidal glycosides, namely cynanotins A–H ( 1 – 8 ), together with fifteen known analogues, were isolated from the roots of Cynanchum otophyllum . Their structures were elucidated by spectroscopic analysis and chemical methods. In this study, all of isolates were tested for their vitro inhibitory activities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480). Compounds 3 – 15 showed moderate cytotoxic activities against HL-60 cell lines with IC 50 values ranging from 11.4 to 37.9 µM. Compounds 5 , 9 , and 10 showed marked or moderate cytotoxic activities against five human tumor cell lines with IC 50 values ranging from 11.4 to 36.7 µM. Compound 11 displayed moderate cytotoxic activities against HL-60, SMMC-7721, MCF-7 and SW480 cell lines with IC 50 values of 12.2–30.8 µM. Compared to the positive control (IC 50 : 35.0 µM), compounds 5 , 9 – 11 exhibited more potential inhibitory activity against MCF-7 cells (IC 50 : 16.1–25.6 µM). [ABSTRACT FROM AUTHOR]

Purpose: Ablative hypofractionated radiation therapy (AHFRT) presents a therapeutic advantage compared with conventional fractionated radiation therapy (CFRT) for primary and oligometastatic cancers. However, the underlying mechanisms remain largely unknown. In the present study, we compared the immune alterations in response to AHFRT versus CFRT and examined the significance of immune regulations contributing to the efficacy of AHFRT.Methods and Materials: We established subcutaneous tumors using syngeneic lung cancer and melanoma cells in both immunocompetent and immunocompromised mice and treated them with AHFRT and CFRT under the same biologically equivalent dose.Results: Compared with CFRT, AHFRT significantly inhibited tumor growth in immunocompetent, but not immunocompromised, mice. On the cellular level, AHFRT reduced the recruitment of myeloid-derived suppressor cells (MDSCs) into tumors and decreased the expression of programmed death-ligand 1 (PD-L1) on those cells, which unlashed the cytotoxicity of CD8+ T cells. Through the downregulation of vascular endothelial growth factor (VEGF), AHFRT inhibited VEGF/VEGF receptor signaling, which was essential for MDSC recruitment. When combined with anti-PD-L1 antibody, AHFRT presented with greater efficacy in controlling tumor growth and improving mouse survival. By altering immune regulation, AHFRT, but not CFRT, significantly delayed the growth of secondary tumors implanted outside the irradiation field.Conclusions: Targeting MDSC recruitment and enhancing antitumor immunity are crucial for the therapeutic efficacy of AHFRT. When combined with anti-PD-L1 immunotherapy, AHFRT was more potent for cancer treatment. [ABSTRACT FROM AUTHOR]

In early studies, it was shown that HINT2, which sensitizes cells to mitochondrial apoptosis, is down-regulated in hepatocellular carcinoma (HCC) cells (Martin et al., 2006). However, the molecular mechanism of this effect is unknown. Immunohistochemistry revealed that HINT2 expression is relatively low in pancreatic cancer tissues, compared to that in adjacent tissues (P < 0.05). Furthermore, its expression was related to pathological grade and lymph node metastasis (P = 0.0161 and 0.0108, respectively); in addition, down-regulation of HINT2 was found to be associated with relatively poor prognosis in pancreatic cancer patients. Up-regulation of HINT2 was shown to trigger pancreatic cancer cell apoptosis, decrease mitochondrial membrane potential (ΔΨm), promote intracellular reactive oxygen species (ROS) production, and elevate mitochondrial Ca2+ levels. However, co-treatment of HINT2 overexpressing BxPC-3 cells with ruthenium red partially inhibited HINT2-induced apoptosis, which was associated with a reduction in ΔΨm and an increase in intracellular ROS and mitochondrial Ca2+. According to our results, mitochondrial calcium uptake1 and 2 (MICU1 and MICU2) were down-regulated and the essential MCU regulator (EMRE) was up-regulated in cells transduced with Adv-HINT2. Therefore, we deduced that HINT2 triggers apoptosis in pancreatic cancer cells by regulating mitochondrial Ca2+ influx through the mitochondrial calcium uniporter (MCU). In addition, we found that HINT2 can sensitize BxPC-3 and L3.6pl cells to gemcitabine-induced apoptosis and that gemcitabine up-regulates HINT2 expression. This indicates that gemcitabine-induced apoptosis is related to HINT2 levels. [ABSTRACT FROM AUTHOR]

Twenty withanolides, including previously unknown nicanlodes A–M, were isolated from aerial parts of Nicandra physalodes . Their structural elucidations were unambiguously achieved through interpretation of extensive spectroscopic data (NMR and HRMS) and by comparison with literature data. Nicanlodes A and B have an unusual aromatic amine moiety. The isolated compounds were evaluated for their cytotoxicity against five human cancer cell lines. [ABSTRACT FROM AUTHOR]

A facile and robust one-pot approach to prepare a theranostic nanoplatform, based on chelation between Gd3+ and hypericin photosensitizer (PS) and their controlled in situ hydrolysis precipitation, was developed. In this strategy, PS drugs and Gd3+ were directly used as building blocks to construct theranostic nanoparticles, resulting in a greatly increased active substance-loading efficiency and ensuring their theranostic effect. The resulting nanoparticles have multifunction capabilities for nuclear magnetic resonance (NMR) imaging and anticancer activity through adenosine triphosphate (ATP) deprivation and heavy atom effect (HAE)-improved photodynamic therapy (PDT) mechanisms. [ABSTRACT FROM AUTHOR]

The transcriptional coactivator with PDZ binding motif (TAZ) is reported as one of the nuclear effectors of Hippo-related pathways. TAZ is found overexpressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in Intrahepatic Cholangiocarcinoma (ICC). In this study, we found that TAZ is expressed more in ICC tissues than in peritumoral tissue, and a robust expression of TAZ is correlated with a lower overall survival rate of ICC patients after hepatectomy. TAZ knockdown results in an increase in cell apoptosis, a promotion of cell-cycle arrest and a decrease in tumor size and weight in vivo through an increased expression of p53. Vitamin D3 can also inhibit cell proliferation by promoting p53 expression in ICC cells. A reduction in TAZ can also enhance the sensitivity of tumor cells to vitamin D by regulating the p53/CYP24A1 pathway. In conclusion, TAZ is associated with the proliferation and drug-resistance of ICC cells, and could be a novel therapeutic target for the treatment of ICC. [ABSTRACT FROM AUTHOR]

Many reports indicated that the cellular uptaken and photodynamic anti-cancer activity of amino group modified phthalocyanine (Pc) could be greatly improved in the acid environment around cancer cells because such Pc could transfer to their hydrochlorid e protonated form and inhibit the intramolecular photoinduced electron transfer (PET) effect. However, no more researches are carried out to indicate whether this law has the extensive applicability in all kinds of amino modified Phthalocyanines (Pcs). So, here, four amino groups modified Pcs and their hydrochloride or quaternized cationic derivatives, with two kinds of amino groups (phenylamine and benzylamine) substituted were synthesized. Their solubility in aqueous system, cancer cell uptaken ability and photodynamic activities were also systematically compared. Our research results indicated that above law had the extensive applicability in benzylamine amino groups modified Pcs. But for phenylamine amino groups modified ones, the cancer cell uptaken ability and anti-cancer activity of hydrochloride derivatives were obviously decreased comparing with the unmodified Pc because its nitrogen atom was closer to the Pc ring, which would induce its nitrogen atom and the ring to form p–π conjugation system, furthermore, the relatively free state of lone pair electrons of surrounding nitrogen atom leaded to PET strengthening. [ABSTRACT FROM AUTHOR]

Self-assembled organic photosensitive nanoparticles have been widely used in diagnosis and therapeutic of cancer. In this manuscript, a simple but effective method to regulate the self-assemble degree of small charge photosensitive drug was demonstrated. Studies indicated that the ordered self-assembled nanostructures with proper assemble degree can significantly enhances the reactive oxygen species generation efficiency and, thereby, improve the in vitro photodynamic efficacy comparing with the corresponding monomers. [ABSTRACT FROM AUTHOR]

The availability of precisely modulated chemical modifications dramatically affects the physicochemical properties of pristine drugs and should facilitate the amphiphilic self-assembly of prodrugs into supramolecular nanoprodrugs (SNPs). However, rationally designing such prodrugs to achieve favorable clinical outcomes still remains a challenge. Here, a library of prodrugs through site-specific attachment of a variety of lipophilic moieties to the antitumor agent SN-38 (7-ethyl-10-hydroxycamptothecin) is constructed. Taking advantage of the role of hydroxyl groups as solvophilic moieties, these prodrugs exhibit self-assembly in aqueous environments, allowing for the identification of five prodrugs capable of self-assembling into SNPs at high drug concentrations. Importantly, in vivo studies demonstrate that the antitumor activity of the SNPs correlates well with their stability and long-term circulation. In addition, the modular feature of this SNP design strategy offers the opportunity to readily incorporate additional valuable functionalities (e.g., tumor-specific targeting ligands) to the particle surface, which is further exploited to improve antitumor efficacy in mouse xenograft models. Thus, this structure-based reconstruction of SN-38 molecules significantly improves the potency of SNPs for clinical use. These results also provide novel mechanistic insights into the rational design of prodrugs. [ABSTRACT FROM AUTHOR]

In order to improve water-solubility and photodynamic activity of 2(3), 9(10), 16(17), 23(24)-tetra-((amino)methyl)phenoxy)phthalocyaninato-zinc (ZnPc) simultaneously, here, we present the first attempt to introduce heavy atoms (Br and I) to ZnPc though a simple method by synthesizing the hydrobromide and hydriodate protonation salt derivatives of ZnPc. Researches indicated that these protonation salt derivatives of ZnPc can stably disperse in aqueous system for a long time. Furthermore, the internal heavy atom effect from hydriodate in the ZnPc molecules enhances the intersystem crossing (ISC) efficiency of ZnPc during its photo-exciting process. Therefore, the generation of reactive oxygen species (ROSs), especially singlet oxygen ( 1 O 2 ), is significantly improved, which leads to an improved in vitro photodynamic therapy (PDT). [ABSTRACT FROM AUTHOR]

A new docetaxel (DTX) delivery system has been prepared based on calcium phosphate nanoparticles (CaP NPs) and obtained DTX-adsorbed CaP NPs. The DTX-adsorbed CaP NPs were nearly spherical with mean diameter about 200 nm and a negative zeta potential of -18.8 ± 0.5 mV. They can be well dispersed and stable in water for a long time. In addition, the DTX-adsorbed CaP NPs showed higher cytotoxicity in human nonsmall-cell lung cancer (NSCLC) cell lines than that of DTX at the same experimental conditions. Thus, it could be concluded that CaP NPs can be a promising DTX delivery vehicle in NSCLC chemotherapy. [ABSTRACT FROM AUTHOR]

Six new 9,19-cycloartane triterpenes ( 1 – 6 ) were isolated from the aerial parts of Cimicifuga yunnanensis . The new chemical structures were determined by extensive analyses of 1D and 2D NMR spectroscopy. Compounds 1 and 2 are the first 9,19-cycloartane triterpenes characterized by CH 3 -18 shifting from C-13 to C-12 in the Cimicifuga spp. The evaluation of inhibition activity against human HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines indicated that compounds 1 – 6 showed different levels of cytotoxic activities with IC 50 values ranging from 1.2 to 27.8 μm. [ABSTRACT FROM AUTHOR]

Poly(ethylene glycol) (PEG) as a block in polymeric micelles can prolong circulation life and reduce systemic clearance but decrease the cellular uptake. To overcome this limitation, a mixed micelle composed of deoxycholic acid-modified chitooligosaccharide (COS-DOCA) and methoxy poly(ethylene glycol)-polylactide copolymer (mPEG-PDLLA) was designed to load paclitaxel (PTX). The PTX-loaded mixed micelles was prepared by nanoprecipitation method with high drug-loading efficiency of 8.03% and encapsulation efficiency of 97.09% as well as small size (∼40 nm) and narrow size distribution. COS-DOCA/mPEG-PDLLA mixed micelles exhibited the sustained release property. Due to the positive charge and bioadhesive property of COS-DOCA, the cellular uptake of PTX in mixed micelles was higher in cancer cells but lower in macrophage cells compared to the mPEG-PDLLA micelles. The systemic toxicity of PTX in mixed micelles was much lower than Taxol using zebrafish as a toxicological model. Furthermore, the PTX-loaded COS-DOCA/mPEG-PDLLA mixed micelles can prolong the blood circulation time of PTX and enhance the antitumor efficacy in A549 lung xenograft model. Our findings indicate that COS-DOCA/mPEG-PDLLA mixed micelles could be a potential vehicle for enhanced delivery of anticancer drugs. [ABSTRACT FROM AUTHOR]

Drug-loaded nanoparticles (NPs) are of particular interest for efficient cancer therapy due to their improved drug delivery and therapeutic index in various types of cancer. However, the encapsulation of many chemotherapeutics into delivery NPs is often hampered by their unfavorable physicochemical properties. Here, we employed a drug reform strategy to construct a small library of SN-38 (7-ethyl-10- hydroxycamptothecin)-derived prodrugs, in which the phenolate group was modified with a variety of hydrophobic moieties. This esterification fine-tuned the polarity of the SN- 38 molecule and enhanced the lipophilicity of the formed prodrugs, thereby inducing their self-assembly into biodegradable poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEGPLA) nanoparticulate structures. Our strategy combining the rational engineering of prodrugs with the pre-eminent features of conventionally used polymeric materials should open new avenues for designing more potent drug delivery systems as a therapeutic modality. [ABSTRACT FROM AUTHOR]

Abstract: Six new cucurbitane-type triterpenoids, karavilagenin F (1), karavilosides XII and XIII (2, 3), momordicines VI, VII, and VIII (4, 5 and 6), along with four known ones, 5β,19-epoxy-25-methoxycucurbita-6,23-diene-3β,19-diol (7), 5β,19-epoxycucurbita-6, 23-diene-3β,19,25-triol (8), kuguacin R (9), and (19R,23E)-5β,19-epoxy-19-methoxycucurbita-6,23,25-trien-3β-ol (10), were isolated from the stems and leaves of Momordica charantia L. Their chemical structures were elucidated by extensive 1D NMR and 2D NMR (HSQC, HMBC, COSY, and ROESY), MS experiments, and CD spectrum. Compound 6 showed weak cytotoxicity against five human cancer cells lines with IC50 values of 14.3–20.5μmol/L. [Copyright &y& Elsevier]

Abstract: Combining different treatment modalities is widely employed in oncology to improve the therapeutic response. In this work, we develop a multifunctional complex for co-delivery of the anticancer drug Ga(NO3)3 and the photosensitizer hypocrellin A (HA) as potential dual delivery system for the combination of chemotherapy and photodynamic therapy (PDT). Ga(NO3)3 is used in cancer treatment and is synergistic with other anticancer drugs. Hypocrellin A is a natural photosensitizer, which has been extensively and intensively studied as a promising PDT agent. HA can chelate with gallium ion to form a 1:1 complex. Irradiation of the complex with light of suitable wavelength results in efficient generation of singlet oxygen (1O2). In vitro studies have demonstrated the active uptake of the complex into the cytosol of tumor cells. Viability of cells treated with the complex decreased as compared to free HA or Ga(NO3)3, thus showing a combined effect of both HA and Ga(NO3)3. [Copyright &y& Elsevier]

Background Maintenance therapy for extensive stage small cell lung cancer ( ES-SCLC) is still under debate. Many new agents fail during the maintenance course. As an active agent for SCLC, oral etoposide is worth being re-evaluated. Methods This phase II study was performed to evaluate the toxicity/efficacy of the maintenance of patients with oral etoposide with ES-SCLC responding (complete remission [ CR] + partial remission [ PR]) to the induction of four cycles of etoposide plus cisplatin ( EP) chemotherapy. Maintenance therapy with oral etoposide (50 mg/m2, day 1-14, repeated every 21 days until disease progression or unacceptable toxicity occurs) was administered. The primary endpoints were grade 3 and 4 toxicities and progression free survival ( PFS). Results Fifty-four patients with ES-SCLC received standard EP regimens as induction therapy; 31 responding patients were administered oral etoposide as the maintenance treatment. The most common hematological and non-hematological toxicity of the maintenance course was neutropenia and fatigue, respectively. Median PFS was nine months (95% confidence interval ( CI): 8.33∼9.67 months), median overall survival ( OS) was 14 months (95% CI: 11.58∼16.42 months). Significantly better PFS and OS were seen in patients responding to the induction EP chemotherapy. Conclusions Oral etoposide maintenance is safe and effective for patients with ES-SCLC who responded to the induction of EP chemotherapy. Significant survival benefit was revealed in patients completely responding to an EP regimen. Further randomized control study is warranted. [ABSTRACT FROM AUTHOR]

Abstract: The complex of Hypocrellin A with Al3+ is prepared in water solution by a facile method. The water-solubility and stability of complexes are improved. Irradiation of Al3+–HA complex results in higher efficient generation of singlet oxygen (1O2) and photocleavage ability to CT DNA than HA. In vitro studies have illustrated that the Al3+–HA complex has anti-cancer activity. [Copyright &y& Elsevier]

Abstract: Novel tetra-substituted zinc phthalocyanines (Pcs) bearing 1,2-ethanediamine group and the quaternized derivatives were synthesized and characterized. The photophysical and cellular properties of these Pcs were investigated. The results indicated that the quaternized ionic effect can greatly improve the water-solubility of Pcs and reduce their aggregation degree in aqueous solution. Comparative studies with quaternized phthalocyanine and its unquaternized counterpart have also demonstrated that the quaternary action on the molecules significantly enhances the fluorescence quantum yields, fluorescence lifetimes, efficiency of singlet oxygen production and, thereby, the in vitro photodynamic therapy efficacy. [Copyright &y& Elsevier]

Abstract: Hypocrellin A is an efficient photodynamic agent against many tumor cells and viruses. However, it was found that the preparation of injectable formula for HA was highly hampered by the poor water solubility of these compounds. So, here, a new water-soluble vanadyl–hypocrellin A complex was first synthesized and the complex forming process was studied using spectral and thermal dynamics methods. The results indicated that VO2+–HA can stable in aqueous solutions and exhibit increased photostability, affinity and photocleavage ability toward ctDNA under anaerobic condition. Moreover, in vitro studies illustrated that VO2+–HA also had strong anti-cancer activity. [Copyright &y& Elsevier]

Abstract: Twelve limonoids, toonayunnanins A–L (1–12) and eleven known compounds (13–23) were isolated from the leaves of Toona ciliata var. yunnanensis, and their structures were elucidated by means of extensive spectroscopic analyses, particularly 1D and 2D NMR techniques. The inhibitory effects of all the isolated compounds were evaluated on human tumor cell lines, such as HL-60, SMMC-7721, A-549, MCF-7 and SW480. Cedrelone (13) and dysobinin (18) showed significant cytotoxicity, and toonayunnanin B (2) and epoxyazadiradione (14), were found to be slightly cytotoxic against the above cell lines. Furthermore, this study provides valuable information for the chemotaxonomy of T. ciliata varieties. [Copyright &y& Elsevier]

Abstract: A new 4α-methyl sterol, cimisterol A (1), together with five known compounds (2–6), were isolated from the aerial parts of Cimicifuga foetida L. The new compound''s structure was determined with the help of extensive 1D and 2D NMR spectroscopy. Compound 1 exhibited broad-spectrum and potent cytotoxic activities against human HL-60, Jurkat, K562, U937, HepG-2, and SGC-7091 cell lines, with IC50 values of 7.23, 2.89, 6.88, 3.38, 4.21, and 4.89μM, respectively. Compound 3 showed moderate to weak activities to all cell lines, except for SGC-7091, having IC50 values ranging from 13.37 to 17.72μM. This is the first time a cytotoxic 4α-methyl sterol constituent was discovered from Cimicifuga spp. [Copyright &y& Elsevier]

Purpose: B7-DC on tumor cells was demonstrated to promote tumor immunity; however, the precise mechanism responsible for the aberrant B7-DC expression remains unknown. Interferon gamma (IFN-γ) can induce B7-DC expression on macrophages and has been shown to regulate anti-tumor immunity by various mechanisms. This study was designed to investigate the relationship of IFN-γ and B7-DC on tumor cells and further explored the signal transduction pathways involved. Methods: RT-PCR and flow cytometry were used for the analysis of B7-DC expression on various tumor cells. The phosphorylation of p38, ERK1/2, JNK, Akt, and JAK2 was determined by Western blot. Results: IFN-γ markedly up-regulated B7-DC expression on various tumor cells and resulted in the phosphorylation of JAK2, JNK, ERK, p38, and Akt. Inhibition of ERK or JNK pathway significantly decreased IFN-γ-induced B7-DC expression, whereas inhibition of phosphorylation of Akt, p38, and JAK2 had very little effect on IFN-γ-induced B7-DC expression. Conclusions: Our findings demonstrate that the pretreatment of tumor cells with IFN-γ enhances B7-DC expression through ERK and JNK pathways. [ABSTRACT FROM AUTHOR]

• Sulfhydryl modified hyaluronic acid (HA-SH) was synthesized. • DMSO as oxidant participated in disulfide bond crosslink of HA-SH to form hydrogel. • The dissolved drugs in DMSO were loaded inside the hydrogel during the crosslinking. • The drug loaded hydrogel can be used as injectable paratumoral implant. • The implant can sustained release the loaded drugs to suppress the tumor growth. Dimethyl sulfoxide (DMSO) is an excellent solvent for various types of anticancer drugs. Here, beyond that, it can participate in a disulfide bond crosslink between sulfhydryl (-SH) modified hyaluronic acid (HA-SH) molecules to form the hydrogel. Thus, during the above crosslink process, the dissolved drug in DMSO could be effectively loaded inside the hydrogels' porous structures as an injectable peritumoral implant. The loaded drugs can be sustained released through hydrogel swelling and degradation around the tumor tissue to suppress tumor growth. In this paper, the above hydrogel was used as a peritumoral drug-loaded implant for chemotherapeutics, photosensitizer, and photothermal reagent, respectively, for chemotherapy, photodynamic therapy, and photothermal therapy in cancer treatment. Therefore, this DMSO involved HA-SS-HA (HA, hyaluronic acid; -SS-, disulfide bond) hydrogel fabrication method is simple and widely applicable for drug-loaded peritumoral implant preparation. [ABSTRACT FROM AUTHOR]

Cancer remains a leading cause of death worldwide and total number of cases globally is increasing. Novel treatment strategies are therefore desperately required for radical treatment of cancers and long survival of patients. A new technology using high pulsed electric field has emerged from military application into biology and medicine by applying nsPEF as a means to inhibit cancer. However, molecular mechanisms of nsPEF on tumors or cancers are still unclear. In this paper, we found that nsPEF had extensive biological effects in cancers, and clarified its possible molecular mechanisms in vitro and in vivo. It could not only induce cell apoptosis via dependent-mitochondria intrinsic apoptosis pathway that was triggered by imbalance of anti- or pro-apoptosis Bcl-2 family proteins, but also inhibit cell proliferation through repressing NF-κB signaling pathway to reduce expressions of cyclin proteins. Moreover, nsPEF could also inactivate metastasis and invasion in cancer cells by suppressing Wnt/β-Catenin signaling pathway to down-regulating expressions of VEGF and MMPs family proteins. More importantly, nsPEF could function safely and effectively as an anti-cancer therapy through inducing tumor cell apoptosis, destroying tumor microenvironment, and depressing angiogenesis in tumor tissue in vivo. These findings may provide a creative and effective therapeutic strategy for cancers. [ABSTRACT FROM AUTHOR]