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Circular replicase-encoding single-stranded (CRESS) DNA viruses and other circular DNA agents are increasingly found in various samples and animals. A specific class of these agents—termed bovine meat and milk factors (BMMF)—has been supposed to act as a factor in indirect carcinogenesis in humans. Initial observations attributed the BMMF to European cattle breeds and foodstuffs produced thereof. In the present study, blood and fecal samples from African and Asian cattle were examined. BMMF molecules and genomoviruses were detected in all bovids under study. The majority (79%) of the 29 circular elements could be assigned to BMMF groups 1 and 2, whereas CRESS viruses of the family Genomoviridae accounted for the smaller part (21%). Two genomoviruses belong to the genus Gemykibivirus and one to the genus Gemykrogvirus. The remaining three might be considered as novel species within the genus Gemycircularvirus. The majority of all isolated molecules originated from fecal samples, whereas only three derived from blood. The results from this study expand our knowledge on the diversity and presence of circular DNA in different ruminants that serve for food production in many countries over the world.

MiR-4295, located on chromosome 10q25.2, is a unique miRNA with a wide range of biological functions. miR-4295 is widely expressed in vivo, participating in the biological processes of multiple cancers. Although miR-4295 is dysregulated in various cancers, it has also been found to have the function of inhibiting cancer. At the same time, the expression of miR-4295 is related to prognosis and can be affected by numerous factors connecting to the therapeutic effects of various drugs. This article is to better summarize the role of miR-4295 in cancer and review the potential diagnostic, prognostic, and therapeutic value of miR-4295, which may provide insight into subsequent research.

Centella asiatica is well known as an important medicinal plant because of its various pharmacological effects. However, most investigations on C. asiatica focused on the pharmacological activity of its extract or asiatic acid. In the present work, we aimed to explore the bioactive compounds of the whole plants of C. asiatica. As a result, seven compounds including two new flavonol derivates named 4′-hydroxyl-7-methoxyl-6-prenyl-3-O-trans-p-coumaroyl-flavonol (1) and (2R,3R,2″S)-3-furanoyl-brosimacutin E (2), and five known compounds (3-7) were isolated. Their chemical structures were elucidated on the basis of spectroscopic analyses. All the isolates were evaluated for in vitro cytotoxic effects on four human cancer cells including A549, HepG2, SGC-7901 and MCF-7. Among them, compounds 1 and 2 exhibited higher cytotoxic activities on HepG2 and SGC-7901 cells compared with 3-7. And compound 2 showed potential cytotoxic activities on HepG2 and SGC-7901 cells with IC50 values of 4.52 and 7.03 μM, respectively.

Four hitherto unknown triterpenoids, including one euphane, namely wilfordeuphone (1), and three friedelanes, namely wilforic acids G − I (2–4), were isolated from the ethanol extract of the roots of Tripterygium wilfordii. The absolute configuration of 1 was established by single crystal X-ray diffraction. In addition, this study is the first to report euphane-type triterpenoid in the genus Tripterygium. Compound 1 exhibited the moderate cytotoxic activity when evaluated against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW-480), with IC50 values ranging from 14.0–26.7 μM.

Certain aspects of experimental tumor models in mice most accurately reflect the biology and immunology of cancer in patients. A survey of experimental cancer immunotherapy papers published in 2020 shows most do not achieve cancer shrinkage although treatment is initiated at an early time point after cancer cell injection, which does not reflect cancer immunotherapy in patients. Even then, few current experimental approaches eradicate the injected malignant cells, most only delay outgrowth. The value of targeting mutation-encoded tumor-specific antigens becomes increasingly evident while problems of finding normal gene-encoded tumor-associated antigens as safe, effective targets persist. It might be time to refocus on realistic experimental settings and truly cancer-specific targets. These antigens are associated with the least risk of side effects.

Plants and associated microorganisms are essential sources of natural products against human cancer diseases, partly exemplified by plant-derived anticancer drugs such as Taxol (paclitaxel). Natural products provide diverse mechanisms of action and can be used directly or as prodrugs for further anticancer optimization. Despite the success, major bottlenecks can delay anticancer lead discovery and implementation. Recent advances in sequencing and omics-related technology have provided a mine of information for developing new therapeutics from natural products. Artificial intelligence (AI), including machine learning (ML), has offered powerful techniques for extensive data analysis and prediction-making in anticancer leads discovery. This review presents an overview of current AI-guided solutions to discover anticancer lead compounds, focusing on natural products from plants and associated microorganisms.

Three new aromadendrane-type sesquiterpenoids (1–3) and five known compounds (4–8) were isolated from the stems of Strophanthus divaricatus. Their structures were determined by spectroscopic methods including HR-ESI-MS, 1D and 2D NMR. The absolute configurations of 1–3 was determined by comparison of the experimental and computed ECD spectra. Neridienone A (6) exhibited significant cytotoxicity against human cancer cell lines BEL-7402, SGC-7901, K562, A549, and HeLa with IC50 values of 3.30 ± 0.01, 2.25 ± 0.01, 2.02 ± 0.03, 1.55 ± 0.01, 4.73 ± 0.07 μM, respectively.

(-)-5-Methylmellein (1) and its new dimer (2) were isolated from cultures of the basidiomycete Inonotus sinensis. Their structures were elucidated on the basis of extensive spectroscopic methods including UV, IR, HR-EI-MS, 1D NMR and 2D NMR. The structure of Compound 2 was determined by single-crystal X-ray crystallographic analysis. Compound 2 was tested for the cytotoxicities against five human cancer cell lines.

Spice-rich recipes are referred to as “functional foods” because they include a variety of bioactive chemicals that have health-promoting properties, in addition to their nutritional value. Using pharmacoinformatics-based analysis, we explored the relevance of bioactive chemicals found in Rasam (a South Indian cuisine) against oxidative stress-induced human malignancies. The Rasam is composed of twelve main ingredients, each of which contains a variety of bioactive chemicals. Sixty-six bioactive compounds were found from these ingredients, and their structures were downloaded from Pubchem. To find the right target via graph theoretical analysis (mitogen-activated protein kinase 6 (MAPK6)) and decipher their signaling route, a network was built. Sixty-six bioactive compounds were used for in silico molecular docking study against MAPK6 and compared with known MAPK6 inhibitor drug (PD-173955). The top four compounds were chosen for further study based on their docking scores and binding energies. In silico analysis predicted ADMET and physicochemical properties of the selected compounds and were used to assess their drug-likeness. Molecular dynamics (MD) simulation modelling methodology was also used to analyse the effectiveness and safety profile of selected bioactive chemicals based on the docking score, as well as to assess the stability of the MAPK6-ligand complex. Surprisingly, the discovered docking scores against MAPK6 revealed that the selected bioactive chemicals exhibit varying binding ability ranges between − 3.5 and − 10.6 kcal mol−1. MD simulation validated the stability of four chemicals at the MAPK6 binding pockets, including Assafoetidinol A (ASA), Naringin (NAR), Rutin (RUT), and Tomatine (TOM). According to the results obtained, fifty of the sixty-six compounds showed higher binding energy (− 6.1 to − 10.6 kcal mol−1), and four of these compounds may be used as lead compounds to protect cells against oxidative stress-induced human malignancies.

Single nucleotide variant (SNV) plays an important role in cellular proliferation and tumorigenesis in various types of human cancer. Next-generation sequencing (NGS) has provided high-throughput data at an unprecedented resolution to predict SNVs. Currently, there exist many computational methods for either germline or somatic SNV discovery from NGS data, but very few of them are versatile enough to adapt to any situations. In the absence of matched normal samples, the prediction of somatic SNVs from single-tumor samples becomes considerably challenging, especially when the tumor purity is unknown. Here, we propose a new approach, STIC, to predict somatic SNVs and estimate tumor purity from NGS data without matched normal samples. The main features of STIC include: (1) extracting a set of SNV-relevant features on each site and training the BP neural network algorithm on the features to predict SNVs; (2) creating an iterative process to distinguish somatic SNVs from germline ones by disturbing allele frequency; and (3) establishing a reasonable relationship between tumor purity and allele frequencies of somatic SNVs to accurately estimate the purity. We quantitatively evaluate the performance of STIC on both simulation and real sequencing datasets, the results of which indicate that STIC outperforms competing methods.

A new paraherquamide named aculeaquamide A (1) was isolated from an EtOAc extract of Aspergillus aculeatinus WHF0198 culture media together with five known compounds. The structures of the isolated compounds were elucidated by analysis of NMR and MS data, and the absolute configurations of compound 1 was confirmed by CD spectroscopic methods. All isolated compounds were evaluated for their cytotoxicity against three human cancer cell lines, Bel-7402, A549, and HCT-116. Compounds 1 and 2 showed cytotoxicity against Bel-7402 with IC50 values of 3.3 and 1.9 μM, respectively.

Euphorbia deflexa, an endemic spurge from Greece, was investigated for the occurrence of its diterpene constituents. Through continuous monitoring by 1H NMR, 22 diterpenoids were isolated, including 16 previously undescribed compounds (euphodeflexins A-P), which belong to the jatrophane, ingenane, segetane, and pepluane diterpene types. Their chemical structures were elucidated through a combination of HRESIMS, NMR spectroscopy, and X-ray data. The isolated diterpenoids were tested against a panel of human cancer cell lines, as well as against two bacterial strains. Compounds 1, 13, and 17 were active against the HeLa cell line with IC50 values 9.9, 9.8, and 5.8 μM, respectively.

With the proliferating studies of human cancers by single-cell RNA sequencing technique (scRNA-seq), cellular heterogeneity, immune landscape and pathogenesis within diverse cancers have been uncovered successively. The exponential explosion of massive cancer scRNA-seq datasets in the past decade are calling for a burning demand to be integrated and processed for essential investigations in tumor microenvironment of various cancer types. To fill this gap, we developed a database of Cancer Single-cell Expression Map (CancerSCEM, https://ngdc.cncb.ac.cn/cancerscem), particularly focusing on a variety of human cancers. To date, CancerSCE version 1.0 consists of 208 cancer samples across 28 studies and 20 human cancer types. A series of uniformly and multiscale analyses for each sample were performed, including accurate cell type annotation, functional gene expressions, cell interaction network, survival analysis and etc. Plus, we visualized CancerSCEM as a user-friendly web interface for users to browse, search, online analyze and download all the metadata as well as analytical results. More importantly and unprecedentedly, the newly-constructed comprehensive online analyzing platform in CancerSCEM integrates seven analyze functions, where investigators can interactively perform cancer scRNA-seq analyses. In all, CancerSCEM paves an informative and practical way to facilitate human cancer studies, and also provides insights into clinical therapy assessments.

Embryonic ectoderm development (EED) is a promising therapeutic target for human cancers and other diseases. We report herein the discovery of exceptionally potent and efficacious EED inhibitors. By conformational restriction of a previously reported EED inhibitor, we obtained a potent lead compound. Further optimization of the lead yielded exceptionally potent EED inhibitors. The best compound EEDi-5273 binds to EED with an IC(50) value of 0.2 nM and inhibits the KARPAS422 cell growth with an IC(50) value of 1.2 nM. It demonstrates an excellent PK and ADME profile, and its oral administration leads to complete and persistent tumor regression in the KARPAS422 xenograft model with no signs of toxicity. Co-crystal structures of two potent EED inhibitors with EED provide a solid structural basis for their high-affinity binding. EEDi-5273 is a promising EED inhibitor for further advanced preclinical development for the treatment of human cancer and other human diseases.

Aloe saudiarabica and Aloe shadensis are a rare species of the genus Aloe found only in Saudi Arabia. The cytotoxic activity of both plants were evaluated in the current study using three different human cancer cell line, lung carcinoma (A-549), breast adenocarcinoma (MCF-7) and liver cancer (HepG2), assessed by WST-1 cell viability assays. The results indicate that the Aloe saudiarabica and Aloe shadensis showed weak cytotoxic effects against all three tested cancer cell lines, with an IC50 value of >300 μg/ml. In addition, HepG2 cells were more sensitive to Aloe saudiarabica treatment than MCF-7 and A549 cells, while MCF-7 cells were more sensitive to Aloe shadensis treatment than HepG2 and A549 cells. This study also identified the characteristic chemical constituents of the two plants using gas chromatography-mass spectrometry technique and the result indicated that 9-octadecenoic acid (Z)-, methyl ester (32.23%) was the main compound of Aloe saudiarabica while methyl 9-octadecenoate (17.28%) was the main compound of Aloe shadensis. In conclusion, the in vitro evaluation of Aloe saudiarabica and Aloe shadensis methanolic extraction showed low cytotoxicity on the viability of A-549, MCF-7 and HepG2 cell lines.

The APRIL molecule, produced by immune cells, their precursors, and cancer cells, is one of the important factors that influences the process of survival and proliferation of cancer cells. In the present review, we summarize the current knowledge on the effects of APRIL on human cancer development and develop a scheme demonstrating the mechanism of the action of APRIL on solid tumors. Understanding the effects of APRIL, including the intracellular signal transduction pathway, may be key for the use of this protein as a biomarker of the cancer process. The correlations observed between APRIL levels and cancer parameters (e.g., disease stage and presence of malignant phenotypes) indicate that APRIL may play an important role, not only in the diagnostic process, but also as a therapeutic target in various cancers.

Many studies have proven the power of gene expression profile in cancer identification, however, the explosive growth of genomics data increasing needs of tools for cancer diagnosis and prognosis in high accuracy and short times. Here, we collected 6136 human samples from 11 cancer types, and integrated their gene expression profiles and protein–protein interaction (PPI) network to generate 2D images with spectral clustering method. To predict normal samples and 11 cancer tumor types, the images of these 6136 human cancer network were separated into training and validation dataset to develop convolutional neural network (CNN). Our model showed 97.4% and 95.4% accuracies in identification of normal versus tumors and 11 cancer types, respectively. We also provided the results that tumors located in neighboring tissues or in the same cell types, would induce machine make error classification due to the similar gene expression profiles. Furthermore, we observed some patients may exhibit better prognosis if their tumors often misjudged into normal samples. As far as we know, we are the first to generate thousands of cancer networks to predict and classify multiple cancer types with CNN architecture. We believe that our model not only can be applied to cancer diagnosis and prognosis, but also promote the discovery of multiple cancer biomarkers.

Pancreatic cancer (PC) is an aggressive human cancer. Appropriate methods for the diagnosis and treatment of PC have not been found at the genetic level, thus making epigenetics a promising research path in studies of PC. Histone methylation is one of the most complicated types of epigenetic modifications and has proved crucial in the development of PC. Histone methylation is a reversible process regulated by readers, writers, and erasers. Some writers and erasers can be recognized as potential biomarkers and candidate therapeutic targets in PC because of their unusual expression in PC cells compared with normal pancreatic cells. Based on the impact that writers have on the development of PC, some inhibitors of writers have been developed. However, few inhibitors of erasers have been developed and put to clinical use. Meanwhile, there is not enough research on the reader domains. Therefore, the study of erasers and readers is still a promising area. This review focuses on the regulatory mechanism of histone methylation, and the diagnosis and chemotherapy of PC based on it. The future of epigenetic modification in PC research is also discussed.

A series of diversely polyfunctionalized pyrazolo[3,4-b]pyridines were synthesized by the multicomponent reaction of phenyl/benzothiazolylhydrazine and 3-oxo-3-arylpropanenitrile with 1,3-diketones...

A novel series of 4,5-dihydroisoxazole-5-carboxamide derivatives were designed, synthesized and evaluated for their anti-cancer activity against two different human cancer cell lines. Most of the synthesized compounds showed anti-cancer activity with IC50 values ranging from 4.03 to 104.45 ��M. Further, compounds 17h, 17i, 17e, and 18e were showed potent inhibitory activity against two cancer cell lines, with IC50 values close to that of standard drug. It is important to note that compound 17h was more potent than the standard drug cisplatin with IC50 values of 4.11 and 4.03 ��M against Hela cell line and MCF-7 cell line respectively.

Some lncRNA-associated competing endogenous RNAs (ceRNAs) are considered as potential biomarkers for targeted therapies and prognosis in human cancer. In our present study, we aimed to construct a ceRNA network and establish a genomic-clinicopathologic nomogram to provide insights into the molecular mechanisms and predict survival for HBV-related HCC. The Cancer Genome Atlas (TCGA) database was applied to collect the data of LIHC RNA-seq dataset and miRNA-seq dataset as well as the clinicopathological information. Identification of differentially expressed RNAs (mRNAs, lncRNAs, and miRNAs) between HBV-related HCC samples and normal samples was conducted using Limma package in R. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for performing the functional enrichment analysis of differentially expressed mRNAs. The ceRNA network was carried out using Cytoscape. The LASSO-penalized Cox regression analysis was implemented to identify HCC-related lncRNAs, and the multivariate Cox regression analysis was conducted for the establishment of a genomic-clinicopathology nomogram. A total of 1859 DEmRNAs, 113 DElncRNAs, and 89 DEmiRNAs were screened out etween HBV-related HCC samples and normal samples. A ceRNA network including 44 DEmRNAs, 7 DElncRNAs, and 20 DEmiRNAs was constructed. 7 DElncRNAs (PVT1, LINC01138, LINC02499, AL355488.2, FGF14-AS2, MAFG-AS1 and LINC00261) were finally identified as prognostic indicators. The area under the curve reached 0.8169 for the 7-lncRNA signature. The predictive accuracy and clinical application value were remarkably high for the genomic-clinicopathologic nomogram integrating the histological grade and the 7-gene-based prognostic index. Taken together, we have established a ceRNA network with HBV-related HCC-specific DElncRNAs, DEmiRNAs, and DEmRNAs. Furthermore, the genome-wide data of lncRNA expression were analyzed using the TCGA database, and a 7-lncRNA signature was identified as a potential prognostic predictor for HBV-related HCC patients. Novel functional studies were provided by our current findings for elucidating the molecular mechanism of lncRNA in HBV-related HCC.

Introduction Proteomics has played a pivotal role in identifying proteins perturbed in disease conditions when compared with healthy samples. Study of dysregulated proteins aids in identifying diagnostic markers and potential therapeutic targets. Cancer is an outcome of interplay of several such disarrayed proteins and molecular pathways which perturb cellular homeostasis, resulting in transformation. In this review, we discuss various facets of proteomic approaches, including tools and technological advancements, aiding in understanding differentially expressed molecules and signaling mechanisms. Areas covered In this review, we have taken the approach of documenting the different methods of proteomic studies, ranging from labeling techniques, data analysis methods, and the nature of molecule detected. We summarize each technique and provide a glimpse of cancer research carried out using them, highlighting the advantages and drawbacks in comparison with others. Literature search using online resources, such as PubMed and Google Scholar were carried out for this approach. Expert opinion Technological advancements in proteomics studies have come a long way from the study of two-dimensional mapping of proteins separated on gels in the early 1970s. Higher precision in molecular identification and quantification (high-throughput), and greater number of samples analyzed have been the focus of researchers.

In recent years fifteen 5,6-dihydro-α-pyrone derivatives, bearing either a distinctive cyclopropane or furan ring and named brevipolides A–O (1–15), have been isolated from the invasive plant Hyptis brevipes Poit. Their fascinating structural features, and the potent biological activities, including cytotoxicity against an array of human cancer cell lines and inhibition of the chemokine receptor CCR5, make them attractive synthetic targets. This review article highlights the recent synthetic methodologies and briefly summarizes their biological activities.

A new tyramine derivative, glycosamide A (1), together with two known amide alkaloids, N-benzoyltyramine methyl ether (2) and aurantiamide acetate (3), was isolated from the branches and leaves of Glycosmis craibii Tanaka. Their structures were elucidated through extensive 1D and 2D NMR and HR-ESI-MS spectroscopic analyses. All known compounds were isolated from the genus Glycosmis for the first time. Furthermore, the antiproliferative activities of all isolated alkaloids in vitro were evaluated. Compound 2 displayed weak antiproliferative activities against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW480.

UNC5 receptor family (UNC5A-D) have been identified as dependence receptors whose functions depend on the availability of their ligand netrin-1. Through binding to netrin-1, these receptors transmit signals for cell survival, migration and differentiation, and participate in diverse physiological and pathological processes. In the lack of netrin-1, however, these receptors initiate apoptosis-inducing signal. Accumulating evidence reveals that netrin-1 and its receptors play a role in tumorigenesis and tumor progression. The expression of UNC5 receptor family is down-regulated in a variety of human tumors. Expression aberrance of UNC5 receptor family in tumors is caused by diverse mechanisms including genomic, epigenetic, transcriptional and post-transcriptional regulation. Notably, blocking netrin-1 binding to its receptors induces apoptotic cell death in tumor cells. In this review, we describe the characters and roles of UNC5 family members in tumorigenesis and tumor progression, discussing the regulatory mechanisms underlying down-regulation of UNC5 family members as well as recent implications of targeting netrin-1/UNC5 on potential clinical application for cancer treatment.

The significant function of circRNAs in cancer was recognized in recent work, so a well-organized resource is required for characterizing the interactions between circRNAs and other functional molecules (such as microRNA and RNA-binding protein) in cancer. We previously developed cancer-specific circRNA database (CSCD), a comprehensive database for cancer-specific circRNAs, which is widely used in circRNA research. Here, we updated CSCD to CSCD2 (http://geneyun.net/CSCD2 or http://gb.whu.edu.cn/CSCD2), which includes significantly more cancer-specific circRNAs identified from a large number of human cancer and normal tissues/cell lines. CSCD2 contains >1000 samples (825 tissues and 288 cell lines) and identifies a large number of circRNAs: 1 013 461 cancer-specific circRNAs, 1 533 704 circRNAs from only normal samples and 354 422 circRNAs from both cancer and normal samples. In addition, CSCD2 predicts potential miRNA–circRNA and RBP–circRNA interactions using binding motifs from >200 RBPs and 2000 microRNAs. Furthermore, the potential full-length and open reading frame sequence of these circRNAs were also predicted. Collectively, CSCD2 provides a significantly enhanced resource for exploring the function and regulation of circRNAs in cancer.

Altered A-to-I RNA editing has been widely observed in many human cancers and some editing sites are associated with drug sensitivity, implicating its therapeutic potential. Increasing evidence has demonstrated that a quantitative trait loci mapping approach is effective to understanding the genetic basis of RNA editing. We systematically performed RNA editing quantitative trait loci (edQTL) analysis in 33 human cancer types for >10 000 cancer samples and identified 320 029 edQTLs. We also identified 1688 ed-QTLs associated with patient overall survival and 4672 ed-QTLs associated with GWAS risk loci. Furthermore, we demonstrated the associations between RNA editing and >1000 anti-cancer drug response with ∼3.5 million significant associations. We developed GPEdit (https://hanlab.uth.edu/GPEdit/) to facilitate a global map of the genetic and pharmacogenomic landscape of RNA editing. GPEdit is a user-friendly and comprehensive database that provides an opportunity for a better understanding of the genetic impact and the effects on drug response of RNA editing in cancers.

The rapid adoption of next-generation sequencing in clinical oncology has enabled the detection of molecular biomarkers shared between multiple tumor types. These pan-cancer biomarkers include sequence-altering mutations, copy number changes, gene rearrangements, and mutational signatures and have been demonstrated to predict response to targeted therapy. This article reviews issues surrounding current and emerging pan-cancer molecular biomarkers in clinical oncology: technological advances that enable the broad detection of cancer mutations across hundreds of genes, the spectrum of driver and passenger mutations derived from human cancer genomes, and implications for patient care now and in the near future.

Eribulin, an inhibitor of microtubule dynamics, is known to show antitumor effects through its remodeling activity in the tumor vasculature. However, the extent to which the improvement of tumor hypoxia by eribulin affects radio-sensitivity remains unclear. We utilized 1-(2,2-dihydroxymethyl-3-18F-fluoropropyl)-2-nitroimidazole (18F-DiFA), a new PET probe for hypoxia, to investigate the effects of eribulin on tumor hypoxia and evaluate the radio-sensitivity during eribulin treatment. Mice bearing human breast cancer MDA-MB-231 cells or human lung cancer NCI-H1975 cells were administered a single dose of eribulin. After administration, mice were injected with 18F-DiFA and pimonidazole, and tumor hypoxia regions were analyzed. For the group that received combined treatment with radiation, 18F-DiFA PET/CT imaging was performed before tumors were locally X-irradiated. Tumor size was measured every other day after irradiation. Eribulin significantly reduced 18F-DiFA accumulation levels in a dose-dependent manner. Furthermore, the reduction in 18F-DiFA accumulation levels by eribulin was most significant 7 days after treatment. These results were also supported by reduction of the pimonidazole-positive hypoxic region. The combined treatment showed significant retardation of tumor growth in comparison with the control, radiation-alone, and drug-alone groups. Importantly, tumor growth after irradiation was inversely correlated with 18F-DiFA accumulation. These results demonstrated that 18F-DiFA PET/CT clearly detected eribulin-induced tumor oxygenation and that eribulin efficiently enhanced the antitumor activity of radiation by improving tumor oxygenation.

Cytotoxicity and antibacterial activities of Euphorbia schimperiana total extract, fractions, and isolated secondary metabolites were investigated. The cytotoxicity assays were assessed against four human cancer cell lines HCT116, MCF7, HePG2, and PC3 as well as against normal cell line RPE1. The plant total extract, fractions, and pure compounds were more effective against PC3 and HepG2 cell lines than HCT116 and MCF7. Significant results were observed for ethyl acetate and n-hexane fractions against PC3 with IC50 of 4.7 μg/ml for ethyl acetate, however, n-hexane exhibited 100% cytotoxicity up to 6.25 μg/ml. The antibacterial potential activity was achieved on four pathogenic Gram-positive and four Gram-negative bacteria. The results showed that ethyl acetate and n-butanol fractions had more valuable results (p

Cancer models are essential in cancer research and for new drug development pipelines. However, conventional cancer tissue models have failed to capture the human cancer physiology, thus hindering drug discovery. The major challenge is the establishment of physiologically relevant cancer models that reflect the complexity of the tumor microenvironment (TME). The TME is a highly complex milieu composed of diverse factors that are associated with cancer progression and metastasis, as well as with the development of cancer resistance to therapeutics. To emulate the TME, 3D bioprinting has emerged as a way to create engineered cancer tissue models. Bioprinted cancer tissue models have the potential to recapitulate cancer pathology and increased drug resistance in an organ-mimicking 3D environment. This review overviews the bioprinting technologies used for the engineering of cancer tissue models and provides a future perspective on bioprinting to further advance cancer research.

Two new merosesquiterpenes, hippomeroterpenes A and B (1 and 2), and four known compounds langconol B (3), 20-demethoxy-20-methylaminodactyloquinone D (4), smenospongidine (5), and smenospongic acid (6) were isolated from the sponge Hippospongia fistulosa. Their structures were determined by extensive analyses of HR ESI MS and NMR spectral data. At concentration of 100 μM, compounds 1-6 exhibited weak cytotoxic effects on Hep-G2, MCF-7, SK-LU-1, and SK-Mel-2 human cancer cells with percentages of dead cells ranging from 8.3 ± 0.3%–36.3 ± 1.5 %.

Two new homosioflavonoids, ophiopogonanone I (1) and methylophiopogonanone C (2) were isolated from the tuberous roots of Ophiopogon japonicus. Their structures were elucidated on the basis of extensive spectroscopic analyses. The absolute configuration of compounds 1 and 2 were assigned on the basis of CD method. In addition, compounds 1–2 were tested for their cytotoxic activities against HL-60, SMMC-7721, and MCF-7 human cancer cell lines, and compound 2 showed significant cytotoxic activity against HL-60 cell line with IC50 value of 14.42 μM.

Callicarpa macrophylla Vahl. has widely been used in traditional medicine for the treatment such as gastrointestinal hemorrhage, coughing up blood, vomiting blood, nosebleeds, swollen and painful fall, rheumatism, bone pain, etc. The crude extract of the stem, leaves and fruits of Callicarpa macrophylla Vahl have exhibited demonstrated cytotoxicity against three human cancer cell lines (Lu-1, Hep-G2 va MCF-7) was tested by SRB assay with CS (%) values ranging from 30,23 ± 1,5 to 90,22 ± 0,15%. Inside, The methanol extract of the leaves of Callicarpa macrophylla Vahl have showed relatively potent cytotoxicity with CS (%) values ranging from 30,23 ± 1,5 to 47,84 ± 2,1%. The n-hexane fraction (L.CM.H) of the leaves of Callicarpa macrophylla Vahl have exhibited potent against three human cancer cell lines (Lu-1, Hep-G2 va MCF-7) than ethyl acetate fraction (L.CM.E) and methanol fraction (L.CM.M) with CS (%) values ranging from 12,49 ± 1,4 to 20,18 ± 0,8%.

Tumour formation involves random mutagenic events and positive evolutionary selection acting on a subset of such events, referred to as driver mutations. A decade of careful surveying of tumour DNA using exome-based analyses has revealed a multitude of protein-coding somatic driver mutations, some of which are clinically actionable. Today, a transition towards whole-genome analysis is well under way, technically enabling the discovery of potential driver mutations occurring outside protein-coding sequences. Mutations are abundant in this vast non-coding space, which is more than 50 times larger than the coding exome, but reliable identification of selection signals in non-coding DNA remains a challenge. In this Review, we discuss recent findings in the field, where the emerging landscape is one in which non-coding driver mutations appear to be relatively infrequent. Nevertheless, we highlight several notable discoveries. We consider possible reasons for the relative absence of non-coding driver events, as well as the difficulties associated with detecting signals of positive selection in non-coding DNA.

Studies have found that lncRNA SENCR (lncSENCR) is closely related to the progress of human cancer. This study aimed to investigate the biological and clinical roles of lncSENCR in non-small cell l...

A phytochemical study of the stems of Homalium stenophyllum Merr. & Chun led to the isolation of two new phenolic glycosides (1 and 2) and three known compounds (3–5). The molecular structures of these isolated new phenolic glycosides (1 and 2) were unambiguously established on the basis of comprehensive spectroscopic methods. All the isolated new compounds were evaluated for their cytotoxicities against three human cancer cell lines: HeLa, A-549, and MCF-7 in vitro.

A series of 1-((1aryl)-1H-1,2,3-triazol-4-yl)methyl)quinoxalin-2(1H)-ones have been synthesized in moderate to high yields and evaluated for their anti-bacterial and anti-cancer activities. Among all the derivatives tested, the compound 1-((1-(2-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)quinoxalin-2(1H)-one exhibited most potent anti-bacterial activity against B. subtilis and S. epidermidis with and also demonstrated comparable inhibitory activity against S. aureus to that of the standard streptomycin. Also, compound 1-((1-(2,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)quinoxalin-2(1H)-one effectively inhibited the gram-positive S. epidermidis equal to that of the standard streptomycin and moderate activity against B. subtilis and S. aureus. Furthermore the compound1-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)quinoxalin-2(1H)-one has shown superior activity against E. coli and moderate activity against B. subtilis, S. epidermidis, and S. aureus when compared with positive control. Moreover, all these compounds were screened for their anti-cancer activity against human cancer cell lines via MCF-7 (breast), A-549 (lungs) and HeLa (cervical). In vitro anti-cancer activity reveals that a few compounds exhibited potent inhibitory in a variety of cancer cell lines. Among the compounds 1-((1-(2,4-dimethoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)quinoxalin-2(1H)-one shown more potent anti-cancer activity against all tested cancer cell lines compared to standard drug, the remaining compounds1-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)quinoxalin2(1H)-one and 1-((1-(2,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)quinoxalin-2(1H)-one exhibited promising anti-cancer activity compared to the other tested compounds.

In search of the best anticancer agents, a series of novel fused [1,2,3]triazolo[4',5':3,4] pyrrolo[2,1-f]purine derivatives in one vessel was synthesized using 8-bromo-1,3-dimethyl-7-(prop-2-yn-1-yl)-1H-purine-2,6(3H,7H)-dione and various arylazides. The newly synthesized derivatives were evaluated for their in vitro anti-proliferative activity against four human cancer cell lines (MCF-7, HeLa, A-549 and U-87MG). 3-(3,5-dichlorophenyl)-5,7-dimethyl-7,10-dihydro-[1,2,3]triazolo[4',5':3,4]pyrrolo[2,1-f]purine-6,8(3H,5H)-dione and 5,7-dimethyl-3-(4-nitrophenyl)-3,10-dihydro-[1,2,3]triazolo[4',5':3.4]pyrrolo[2,1-f]purine-6,8 (5H,7H)-dione are showed stronger activity against MCF-7 and A-549 with IC50 values ranging from 11.5 ± 0.64 to 15.3 ± 0.81 μM, which are comparable to the standard drug doxorubicin. Molecular docking studies have also been conducted to complement the experimental results.

RAS mutations (HRAS, NRAS, and KRAS) are among the most common oncogenes, and around 19% of patients with cancer harbor RAS mutations. Cells harboring RAS mutations tend to undergo malignant transformation and exhibit malignant phenotypes. The mutational status of RAS correlates with the clinicopathological features of patients, such as mucinous type and poor differentiation, as well as response to anti-EGFR therapies in certain types of human cancers. Although RAS protein had been considered as a potential target for tumors with RAS mutations, it was once referred to as a undruggable target due to the consecutive failure in the discovery of RAS protein inhibitors. However, recent studies on the structure, signaling, and function of RAS have shed light on the development of RAS-targeting drugs, especially with the approval of Lumakras (sotorasib, AMG510) in treatment of KRASG12C-mutant NSCLC patients. Therefore, here we fully review RAS mutations in human cancer and especially focus on emerging strategies that have been recently developed for RAS-targeting therapy.

Twelve new [11]-chaetoglobosins, chaetopseudeurins A-L (1-12), were identified from the fermentation of the endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. Compounds 2 and 5-7 exhibited significant cytotoxicities against seven human cancer cell lines, with IC50 values ranging from 4.7 ± 1.0 to 12.2 ± 0.7 μM, and induced G2/M cell cycle arrest and apoptosis in MCF-7 and A427 cells dose dependently. Western blot analysis showed that compound 2 induced apoptosis of MCF-7 cells via the Bcl-2/caspase-3/PARP pathway.

The chemical investigation of Chromolaena palmaris (Sch.Bip. ex Baker) R.M. King & H. Rob. expands the phytochemical composition knowledge of Chromolaena genus, since this is the first chemical investigation of this species. Twenty-five compounds were identified, including a phytoprostane, 17 flavonoids, 6 phenolic acids, and a caffeoyl-glucoside derivative obtained by classical chromatography and UHPLC-HRMS/MS analysis. Moreover, anti-Mycobacterium tuberculosis and antiproliferative activities of C. palmaris were evaluated. Dichloromethane fraction showed cytotoxicity towards human cancer cell lines, presenting TGI values on glioma (U251) of 27.8 μg mL-1. Furthermore, compounds 1 and 2 exhibited antimicrobial activity against Mycobacterium tuberculosis with MIC of 62.5 and 15.6 μg mL-1, respectively.

Two new cycloartane triterpenoids, (24 R)-cycloartane-3β,24,25,30-tetrol (1) and (24 R)-24,25,30-trihydroxy-9,19-cycloartane-3-one (2), along with three known compounds (3-5) were isolated from leaves and twigs of Aphanamixis polystachya. The new compounds were elucidated based on comprehensive spectroscopic analysis, including 1 D, 2 D NMR and HREIMS. The in vitro cytotoxic activities evaluation of five human cancer cell lines revealed that compound 1 exhibited cytotoxic activity on all of tested human cancer cell lines, while compound 2 only had specific activity on SMMC-7721 cell line.

MicroRNA is a small noncoding RNA that plays a role in regulating gene expression. miR-1271 is a tumor suppressor microRNA, which is related to the biological changes of many cancers. miR-1271 is considered a biomarker with a potential prognosis and high therapeutic value in tumors. Besides, the expression of miR-1271 is also regulated by many factors. In this study, we summarize the role of miR-1271 in tumors, focusing on the molecular mechanisms of the target genes of miR-1271. Our review will provide a comprehensive understanding of miR-1271 in tumors, as well as ideas for subsequent tumor research related to miR-1271.

Circular RNAs (circRNAs) are RNAs that have an important role in various pathological processes, including cancer. After the usage of high-throughput RNA sequencing, many circRNAs were found to be differentially expressed in various cancer cell lines and regulate cell signaling pathways by modulating particular gene expressions. Understanding their role in these pathways and what cancers they are found in can set the stage for identifying diagnostic and prognostic biomarkers and therapeutic targets of cancer. This paper will discuss which circRNAs are found in different cancers and what mechanisms they use to upregulate or downregulate certain cellular components.

There is no effective way to detect structure variations (SVs) and extra-chromosomal circular DNAs (ecDNAs) at single-cell whole-genome level. Here, we develop a novel third-generation sequencing platform-based single-cell whole-genome sequencing (scWGS) method named SMOOTH-seq (single-molecule real-time sequencing of long fragments amplified through transposon insertion). We evaluate the method for detecting CNVs, SVs, and SNVs in human cancer cell lines and a colorectal cancer sample and show that SMOOTH-seq reliably and effectively detects SVs and ecDNAs in individual cells, but shows relatively limited accuracy in detection of CNVs and SNVs. SMOOTH-seq opens a new chapter in scWGS as it generates high fidelity reads of kilobases long. Supplementary Information The online version contains supplementary material available at 10.1186/s13059-021-02406-y.

Two dammarane glycosides (1-2) were isolated from the leaves of Cyclocarya paliurus. The structures of new compounds were established by application of spectroscopic methods, including one-dimensional and two-dimensional NMR, HRESIMS, and chemical hydrolysis. When evaluated against seven human cancer cell lines, the two compounds exhibited selective cytotoxicity to MCF-7 cells.

Four undescribed sulfoxide-containing derivatives, sinkiangenoxides A and B, (2Z, 4E)-sinkiangenoxide C, and (2E, 4E)-sinkiangenoxide C (1 – 4), and one known compound, 1-(methylthio)propyl (E)-1-propenyl disulfide (5), were isolated from the resin of Ferula sinkiangensis. Their structures were determined based on spectroscopic methods, including IR, UV, HRESIMS, NMR, and CD analysis. Compounds 2 – 4 showed moderate cytotoxic activities against four human cancer cell lines with IC50 values ranging from 15.0 to 40.3 µM. Sinkiangenoxide B (2) was shown to induce apoptosis in HepG2 cells. In addition, compound 5 effectively attenuated lipopolysaccharide-induced nitric oxide release and TNF-α, IL-1β, IL-6, and IL-10 expression.