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Mesenchymal stem cells (MSCs) are recruited by malignant tumor cells to the tumor microenvironment (TME) and play a crucial role in the initiation and progression of malignant tumors. This role encompasses immune evasion, promotion of angiogenesis, stimulation of cancer cell proliferation, correlation with cancer stem cells, multilineage differentiation within the TME, and development of treatment resistance. Simultaneously, extensive research is exploring the homing effect of MSCs and MSC‐derived extracellular vesicles (MSCs‐EVs) in tumors, aiming to design them as carriers for antitumor substances. These substances are targeted to deliver antitumor drugs to enhance drug efficacy while reducing drug toxicity. This paper provides a review of the supportive role of MSCs in tumor progression and the associated molecular mechanisms. Additionally, we summarize the latest therapeutic strategies involving engineered MSCs and MSCs‐EVs in cancer treatment, including their utilization as carriers for gene therapeutic agents, chemotherapeutics, and oncolytic viruses. We also discuss the distribution and clearance of MSCs and MSCs‐EVs upon entry into the body to elucidate the potential of targeted therapies based on MSCs and MSCs‐EVs in cancer treatment, along with the challenges they face. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells, as innate lymphocytes, possess cytotoxic capabilities and engage target cells through a repertoire of activating and inhibitory receptors. Particularly, natural killer group 2, member D (NKG2D) receptor on NK cells recognizes stress‐induced ligands—the MHC class I chain‐related molecules A and B (MICA/B) presented on tumor cells and is key to trigger the cytolytic response of NK cells. However, tumors have developed sophisticated strategies to evade NK cell surveillance, which lead to failure of tumor immunotherapy. In this paper, we summarized these immune escaping strategies, including the downregulation of ligands for activating receptors, upregulation of ligands for inhibitory receptors, secretion of immunosuppressive compounds, and the development of apoptosis resistance. Then, we focus on recent advancements in NK cell immune therapies, which include engaging activating NK cell receptors, upregulating NKG2D ligand MICA/B expression, blocking inhibitory NK cell receptors, adoptive NK cell therapy, chimeric antigen receptor (CAR)‐engineered NK cells (CAR‐NK), and NKG2D CAR‐T cells, especially several vaccines targeting MICA/B. This review will inspire the research in NK cell biology in tumor and provide significant hope for improving cancer treatment outcomes by harnessing the potent cytotoxic activity of NK cells. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper is to investigate the effect of long noncoding RNA (lncRNA) MIR100HG on the proliferation and metastasis of lung cancer cells by mediating the microRNA (miR)−5590‐3p/DCBLD2 axis. Methods: RNA levels of MIR100HG, miR‐5590‐3p, and DCBLD2 in lung cancer tissues and cells were detected by quantitative reverse‐transcription polymerase chain reaction, and protein level was assessed by Western blot. Effects of MIR100HG or miR‐5590‐3p on proliferation, migration, and invasion of lung cancer cells were detected by Cell Counting Kit‐8, colony formation, and Transwell assays. Luciferase reporter assay and RNA‐immunoprecipitation assay confirmed the target relationship between miR‐5590‐3p and MIR100HG or DCBLD2. Results: MIR100HG and DCBLD2 were highly expressed, while miR‐5590‐3p was lowly expressed in lung cancer tissues and cells. Silencing MIR100HG or upregulating miR‐5590‐3p impeded lung cancer cell proliferation, migration, and invasion. MIR100HG could up‐regulate DCBLD2 by sponging miR‐5590‐3p. Downregulation of miR‐5590‐3p partly overturned the suppressive effect of silencing MIR100HG on lung cancer cell proliferation and metastasis, and overexpression of DCBLD2 also reversed the effect of overexpression of miR‐5590‐3p on lung cancer cell proliferation and metastasis. Conclusion: LncRNA MIR100HG promotes lung cancer progression by targeting and negatively regulating DCBLD2 through binding with miR‐5590‐3p. [ABSTRACT FROM AUTHOR]

Presents a list of articles for publication in future issues of the "European Journal of Biochemistry". Conformation of physalaemin; Association of cross-linked proteins with a specific mRNA in the cytoplasm of HeLa cells; Transport of proteins into chloroplasts.

Chronic Myelogenous Leukaemia (CML) is a haematopoietic stem cells disease with complex dynamical behaviour. One of the effective factors in treating patients is to determine the appropriate drug dosage. A physician should test the different drug dosages through trial and error in order to find its optimal value. This procedure is normally a time‐consuming and error‐prone task that can even be harmful. The contribution of this paper is to design an intelligent control strategy, which can be used to help physicians, by finding a drug treatment regimen to minimize the number of cancer cells for a CML patient. In this paper, the eligibility traces algorithm and Q‐learning approach are adopted as sub‐optimal methods for progressively reducing the population of cancer cells. In addition, the injected dosage of the drug has improved, compared with previous methods. More importantly, the proposed method is followed by the reduction in side effects of the drug. The advantage of the backward view and the previous states investigation are applied in the Eligibility Traces algorithm. These effects increase the learning procedure and decrease the growth rate of cancer cells and total dosage of the injected drug during the treatment period of time. The proposed strategy mitigates the side effects of the drug on the normal cells. [ABSTRACT FROM AUTHOR]

The diagnosis of solid tumors of epithelial origin (carcinomas) represents a major part of the workload in clinical histopathology. Carcinomas consist of malignant epithelial cells arranged in more or less cohesive clusters of variable size and shape, together with stromal cells, extracellular matrix, and blood vessels. Distinguishing stroma from epithelium is a critical component of artificial intelligence (AI) methods developed to detect and analyze carcinomas. In this paper, we propose a novel automated workflow that enables large‐scale guidance of AI methods to identify the epithelial component. The workflow is based on re‐staining existing hematoxylin and eosin (H&E) formalin‐fixed paraffin‐embedded sections by immunohistochemistry for cytokeratins, cytoskeletal components specific to epithelial cells. Compared to existing methods, clinically available H&E sections are reused and no additional material, such as consecutive slides, is needed. We developed a simple and reliable method for automatic alignment to generate masks denoting cytokeratin‐rich regions, using cell nuclei positions that are visible in both the original and the re‐stained slide. The registration method has been compared to state‐of‐the‐art methods for alignment of consecutive slides and shows that, despite being simpler, it provides similar accuracy and is more robust. We also demonstrate how the automatically generated masks can be used to train modern AI image segmentation based on U‐Net, resulting in reliable detection of epithelial regions in previously unseen H&E slides. Through training on real‐world material available in clinical laboratories, this approach therefore has widespread applications toward achieving AI‐assisted tumor assessment directly from scanned H&E sections. In addition, the re‐staining method will facilitate additional automated quantitative studies of tumor cell and stromal cell phenotypes. [ABSTRACT FROM AUTHOR]

In the past few years, the evolution of immunotherapy has resulted in a shift in cancer treatment models. However, with immunosuppressive effects of the tumour microenvironment continues to limit advances in tumour immunotherapy. The tumour microenvironment induces metabolic reprogramming in cancer cells, which results in competition for nutrients between tumour cells and host immunocytes. Metabolic and waste products originating in tumour cells can influence the activation and effector properties of immunocytes in numerous ways and ultimately promote the survival and propagation of tumour cells. In this paper, we discuss metabolic reprogramming in tumour cells and the influence of metabolite by‐products on the immune microenvironment, providing novel insights into tumour immunotherapy. [ABSTRACT FROM AUTHOR]

Inhibition of cyclin‐dependent kinases Cdk4/6 is emerging as a useful anti‐proliferative chemotherapy, but it remains unclear how durable inhibition of cancer cell proliferation is achieved to promote a long‐lasting response in patients, or how toxicity is limited to cancer cells with minimal side effects. Two recent papers in The EMBO Journal investigating senescence induction following prolonged Cdk4/6 inhibitor treatment now reveal important insights into ways to increase anti‐tumour effects of Cdk4/6 inhibition and to reduce therapy‐induced side effects of senescence induction. [ABSTRACT FROM AUTHOR]

This special issue of evolutionary applications focused on the evolution of cancer has provided a wealth of different viewpoints and results from leaders in the field. Together, these papers emphasize the importance of a broad perspective in order to understand why we and other animals get cancer, how it evolves within an individual, and what we can do about it. We can no longer take reductionist approaches that consider only the cancer cells and their genes. Instead, we need to understand how millions of years of evolution have guided strategies that shape cancer risk, why cancer risk varies across different animals, how cancer risk can vary in a population and be influenced by ecology (and influence this ecology), and of course how cancers evolve within us and the evolutionarily informed strategies to counter their impact. My goal here will be to "bring it all home," providing a refresher of lessons learned with added kibitzing. [ABSTRACT FROM AUTHOR]

Image‐based cytometry faces challenges due to technical variations arising from different experimental batches and conditions, such as differences in instrument configurations or image acquisition protocols, impeding genuine biological interpretation of cell morphology. Existing solutions, often necessitating extensive pre‐existing data knowledge or control samples across batches, have proved limited, especially with complex cell image data. To overcome this, "Cyto‐Morphology Adversarial Distillation" (CytoMAD), a self‐supervised multi‐task learning strategy that distills biologically relevant cellular morphological information from batch variations, is introduced to enable integrated analysis across multiple data batches without complex data assumptions or extensive manual annotation. Unique to CytoMAD is its "morphology distillation", symbiotically paired with deep‐learning image‐contrast translation—offering additional interpretable insights into label‐free cell morphology. The versatile efficacy of CytoMAD is demonstrated in augmenting the power of biophysical imaging cytometry. It allows integrated label‐free classification of human lung cancer cell types and accurately recapitulates their progressive drug responses, even when trained without the drug concentration information. CytoMAD also allows joint analysis of tumor biophysical cellular heterogeneity, linked to epithelial‐mesenchymal plasticity, that standard fluorescence markers overlook. CytoMAD can substantiate the wide adoption of biophysical cytometry for cost‐effective diagnosis and screening. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is often considered one of the most aggressive subtypes of breast cancer, characterized by a high recurrence rate and low overall survival (OS). It is notorious for posing challenges related to drug resistance. While there has been progress in TNBC research, the mechanisms underlying chemotherapy resistance in TNBC remain largely elusive. We collect single‐cell RNA sequencing (scRNA‐seq) data from five TNBC patients susceptible to chemotherapy and five resistant cases. Comprehensive analyses involving copy number variation (CNV), pseudotime trajectory, cell–cell interactions, pseudospace analysis, as well as transcription factor and functional enrichment are conducted specifically on macrophages and malignant cells. Furthermore, we performed validation experiments on clinical samples using multiplex immunofluorescence. We identified a subset of SPP1+ macrophages that secrete SPP1 signals interacting with CD44 on malignant cell surfaces, potentially activating the PDE3B pathway within malignant cells via the integrin pathway, leading to chemotherapy resistance. The abnormally enhanced SPP1 signal between macrophages and malignant cells may serve as a factor promoting chemotherapy resistance in TNBC patients. Therefore, SPP1+ macrophages could potentially serve as a therapeutic target to reduce chemotherapy resistance. [ABSTRACT FROM AUTHOR]

Targeting the programmed cell death 1/programmed cell death ligand 1 (PD‐1/PD‐L1) pathway has been identified as a successful approach for tumor immunotherapy. Here, we identified that the small molecule 5,7,4′‐trimethoxyflavone (TF) from Kaempferia parviflora Wall reduces PD‐L1 expression in colorectal cancer cells and enhances the killing of tumor cells by T cells. Mechanistically, TF targets and stabilizes the ubiquitin ligase HMG‐CoA reductase degradation protein 1 (HRD1), thereby increasing the ubiquitination of PD‐L1 and promoting its degradation through the proteasome pathway. In mouse MC38 xenograft tumors, TF can activate tumor‐infiltrating T‐cell immunity and reduce the immunosuppressive infiltration of myeloid‐derived suppressor cells and regulatory T cells, thus exerting antitumor effects. Moreover, TF synergistically exerts antitumor immunity with CTLA‐4 antibody. This study provides new insights into the antitumor mechanism of TF and suggests that it may be a promising small molecule immune checkpoint modulator for cancer therapy. [ABSTRACT FROM AUTHOR]

YT521‐B homology (YTH) domain family (YTHDF) proteins serve as readers that directly recognise m6A modifications. In this study, we aim to probe the role of YTHDF1 in environmental carcinogen‐induced malignant transformation of gastric cells and gastric cancer (GC) carcinogenesis. We established a long‐term low‐dose MNU‐induced malignant transformation model in gastric epithelial cells. In vivo and in vitro experiments were conducted to validate the malignant phenotype and characterise the roles of YTHDF1 and its downstream genes in malignant transformation cells. Additionally, we explored downstream m6A modification targets of YTHDF1 using RNA‐sequencing, RNA immunoprecipitation, and proteomics analyses, and conducted validation experiments in cell experiments and clinical samples. Long‐term low‐dose exposure of MNU converted normal Gges‐1 cells into malignant cells. YTHDF1 mRNA and protein expression are increased in MNU‐induced malignant cells (p<0.001). Meanwhile, YTHDF1 knockdown inhibits the malignant potential of MNU‐treated cells (p<0.01). YTHDF1 knockdown specifically suppresses HSPH1 protein, but not RNA levels. RIP‐qPCR validates HSPH1 is the target of YTHDF1 (p<0.01). HSPH1 knockdown impairs the malignant potential of MNU‐induced transformed cells. The increased expression of the key regulatory factor YTHDF1 in MNU‐induced gastric carcinogenesis affects malignant transformation and tumorigenesis by regulating the translation of downstream HSPH1. These findings provide new potential targets for preventing and treating environmental chemical‐induced gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

The progestin regimen is one of the main therapeutic strategies for women with endometrial cancer who undergo conservative management. Although many patients respond well to initial therapy, progestin‐refractory disease inevitably emerges, and the molecular basis underlying progestin resistance has not been comprehensively elucidated. Herein, they demonstrated progestin results in p38‐dependent IDH1 Thr 77 phosphorylation (pT77‐IDH1). pT77‐IDH1 translocates into the nucleus and is recruited to chromatin through its interaction with OCT6. IDH1‐produced α‐ketoglutarate (αKG) then facilitates the activity of OCT6 to promote focal adhesion related target gene transcription to confer progestin resistance. Pharmacological inhibition of p38 or focal adhesion signaling sensitizes endometrial cancer cells to progestin in vivo. The study reveals p38‐dependent pT77‐IDH1 as a key mediator of progestin resistance and a promising target for improving the efficacy of progestin therapy. [ABSTRACT FROM AUTHOR]

Induction of ferroptosis can inhibit cancer cells in vitro, however, the role of ferroptosis in treatment in vivo is controversial. The immunosuppressive cells activated by the ferroptotic tumor cells can promote the growth of residual tumor cells, hindering the application of ferroptosis stimulation in tumor treatment. In this study, a new strategy is aimed to be identified for effectively triggering immunogenic ferroptosis in pancreatic ductal adenocarcinoma (PDAC) and simultaneously stimulating antitumor immune responses. Toward this, several molecular and biochemical experiments are performed using patient‐derived organoid models and a KPC mouse model (LSL‐KrasG12D/+, LSL‐Trp53R172H/+, Pdx‐1‐Cre). It is observed that the inhibition of macrophage‐capping protein (MCP) suppressed the ubiquitin fold modifier (UFM)ylation of pirin (PIR), a newly identified substrate of UFM1, thereby decreasing the transcription of GPX4, a marker of ferroptosis, and promoting the cytoplasmic transportation of HMGB1, a damage‐associated molecular pattern. GPX4 deficiency triggered ferroptosis, and the pre‐accumulated cytosolic HMGB1 is released rapidly. This altered release pattern of HMGB1 facilitated the pro‐inflammatory M1‐like polarization of macrophages. Thus, therapeutic inhibition of MCP yielded dual antitumor effects by stimulating ferroptosis and activating antitumor pro‐inflammatory M1‐like macrophages. The nanosystem developed for specifically silencing MCP is a promising tool for treating PDAC. [ABSTRACT FROM AUTHOR]

Background: The heterogeneity of tumor endothelial cells (TECs) hinders the efficacy of antiangiogenic therapies (AATs). Only a small percentage of angiogenic TECs are considered effective targets for AATs. Immunomodulatory ECs (IMECs), as a newly focused functional subgroup of endothelial cells (ECs), are being evaluated for their ability to regulate tumor immune balance and influence existing AATs. Methods: Based on single‐cell transcriptome data from colorectal cancer in a publicly available database, we conducted a wide array of bioinformatic approaches to study EC subsets that meet the IMECs definition. Our investigation encompassed the gene expression signatures of these subsets, cellular composition differences, cell–cell interactions. Results: Two subsets that meet the IMECs definition were found in tumors and para‐cancerous tissues. Combined with the results of gene ontological analysis and interaction with CD4+ T cells, we found that IMECs can present MHC‐II antigens to mature CD4+ T cells. There were differences in the level of interaction between IMECs and different types of mature CD4+ T cell subsets. In addition, IMEC subsets had different expression levels of angiogenesis related genes. The angiogenesis score of IMECs decreased after patients received immunotherapy. IMEC subsets do not depend on a single proangiogenic receptor and are involved in regulating angiogenesis, which may reduce the efficacy of AATs. The adverse effects of specific IMEC subsets on AATs were validated in the RNA‐seq dataset of the bevacizumab treatment group. Conclusion: Our study suggests the potential MHC‐II antigen presentation capacity of IMECs and the enhanced angiogenesis characteristics within tumors. The function of IMECs in the vascular network may have a potentially adverse effect on AATs. Controlling the functional properties of IMECs may be a new angle for tumor therapy. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin, a natural compound extracted from the rhizomes of Curcuma longa, displays pronounced anticancer properties but lacks good bioavailability and stability. In a previous study, we initiated structure modification of the curcumin scaffold by imination of the labile β‐diketone moiety to produce novel β‐enaminone derivatives. These compounds showed promising properties for elaborate follow‐up studies. In this work, we focused on another class of nitrogen‐containing curcuminoids with a similar objective: to address the bioavailability and stability issues and to improve the biological activity of curcumin. This paper thus reports on the synthesis of new pyridine‐, indole‐, and pyrrole‐based curcumin analogues (aza‐aromatic curcuminoids) and discusses their water solubility, antioxidant activity, and antiproliferative properties. In addition, multivariate statistics, including hierarchical clustering analysis and principal component analysis, were performed on a broad set of nitrogen‐containing curcuminoids. Compared to their respective mother structures, that is, curcumin and bisdemethoxycurcumin, all compounds, and especially the pyridin‐3‐yl β‐enaminone analogues, showed better water solubility profiles. Interestingly, the pyridine‐, indole‐, and pyrrole‐based curcumin derivatives demonstrated improved biological effects in terms of mitochondrial activity impairment and protein content, in addition to comparable or decreased antioxidant properties. Overall, the biologically active N‐alkyl β‐enaminone aza‐aromatic curcuminoids were shown to offer a desirable balance between good solubility and significant bioactivity. [ABSTRACT FROM AUTHOR]

The pentacyclic acridine RHPS4 is a highly potent and specific G‐quadruplex (G4) ligand, which binds and stabilizes telomeric G4 leading to the block of the replication forks at telomeres and consequently to telomere dysfunctionalization. In turn, the cell recognizes unprotected telomeres as DNA double‐strand breaks with consequent activation of DNA repair response at telomeres, cellular growth impairment, and death. Data from the literature showed the capability of this compound to sensitize U251MG glioblastoma radioresistant cell line to X‐rays sparsely ionizing radiations. In the present paper, it was investigated whether RHPS4 is also able to increase the effect of clinical carbon ion beams (cells irradiated in the middle of a spread‐out Bragg peak, in the energy range of 246–312 MeV·μm−1 and a dose‐averaged linear energy transfer of 46 keV·μm−1). Interestingly, also for charged particles whose damage inflicted to DNA is more complex than that of sparsely ionizing radiations and results in higher Relative Biological Effectiveness (RBE), RHPS4 significantly potentiated the radiation effect in terms of cell killing, delayed rejoining of DNA double‐strand breaks (γ‐H2AX and 53BBP1 immunofluorescence staining), chromosome aberrations (pan‐centromeric/telomeric FISH and multicolor FISH), and G2/M‐phase accumulation in GBM cells. Overall, the results provide the first evidence that the combined administration of the G4‐ligand RHPS4 with charged particles interfere with cellular processes involved in cell survival leading to radiosensitization of highly radioresistant tumor cells. [ABSTRACT FROM AUTHOR]

The Gasdermin protein is a membrane disruptor that can mediate immunogenic pyroptosis and elicit anti‐tumor immune function. However, cancer cells downregulate Gasdermin and develop membrane repair mechanisms to resist pyroptosis. Therefore, an artificial membrane disruptor (AMD) that can directly mediate membrane rupture in pyroptosis‐deficient cells and induce antitumor immune responses in a controllable manner will be valuable in preclinical and clinical research. A micron‐scale Ce6‐based AMD that can directly induce plasma membrane rupture (PMR) in gasdermin‐deficient tumor cells is established. Micron‐scale AMDs localize Ce6 specifically to the plasma membrane without labeling other organelles. Compared to free Ce6 molecules, the use of AMDs results in a higher degree of specificity for the plasma membrane. Due to this specificity, AMDs mediate fast and irreversible PMR under 660 nm red light. Furthermore, the AMDs are capable of inducing programmed cell death and lytic cell death in a catalytic manner, demonstrating that the amount of Ce6 used by AMDs is only one‐fifth of that used by Ce6 alone when inducing 80% of cancer cell death. In vivo, the AMDs show specificity for tumor targeting and penetration, suggesting that light‐driven programmed cell death is specific to tumors. AMDs are applied to antitumor therapy in gasdermin‐deficient tumors, resulting in efficient tumor elimination with minimal damage to major organs when combined with anti‐PD‐1 therapy. Tumor regression is correlated with PMR‐mediated inflammation and T‐cell‐based immune responses. This study provides new insights for designing bioinspired membrane disruptors for PMR and mediating anti‐tumor immunotherapy. Additionally, AMD is a dependable tool for examining the immunogenicity of PMR both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Background and Aims: Pancreatic cancer develops in the normal tissues of the pancreas from malignant cells. The chance of recovery is not good, and the chance of survival 5 years following diagnosis is quite low. Pancreatic cancer treatment strategies such as radiotherapy and chemotherapy had relatively low success rates. Therefore, the present study aims to explore new therapies for treating pancreatic cancer. Methods: The present study searched for information about pancreatic cancer pathophysiology, available treatment options; and their comparative benefits and challenges. Aiming to identify potential alternative therapeutics, this comprehensive review analyzed information from renowned databases such as Scopus, PubMed, and Google Scholar. Results: In recent years, there has been a rise in interest in the possibility that natural compounds could be used as treatments for cancer. Cannabinoids, curcumin, quercetin, resveratrol, and triptolide are some of the anticancer phytochemicals now used to manage pancreatic cancer. The above compounds are utilized by inhibiting or stimulating biological pathways such as apoptosis, autophagy, cell growth inhibition or reduction, oxidative stress, epithelial–mesenchymal transformation, and increased resistance to chemotherapeutic drugs in the management of pancreatic cancer. Conclusion: Right now, surgery is the only therapeutic option for patients with pancreatic cancer. However, most people who get sick have been diagnosed too late to benefit from potentially effective surgery. Alternative medications, like natural compounds and herbal medicines, are promising complementary therapies for pancreatic cancer. Therefore, we recommend large‐scale standardized clinical research for the investigation of natural compounds to ensure their consistency and comparability in pancreatic cancer treatment. [ABSTRACT FROM AUTHOR]

Growth hormone inducible transmembrane protein (GHITM), one member of Bax inhibitory protein‐like family, has been rarely studied, and the clinical importance and biological functions of GHITM in kidney renal clear cell carcinoma (KIRC) still remain unknown. In the present study, we found that GHITM was downregulated in KIRC. Aberrant GHITM downregulation related to clinicopathological feature and unfavourable prognosis of KIRC patients. GHITM overexpression inhibited KIRC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, GHITM overexpression could induce the downregulation of Notch1, which acts as an oncogene in KIRC. Overexpression of Notch1 effectively rescued the inhibitory effect induced by GHITM upregulation. More importantly, GHITM could regulate PD‐L1 protein abundance and ectopic overexpression of GHITM enhanced the antitumour efficiency of PD‐1 blockade in KIRC, which provided new insights into antitumour therapy. Furthermore, we also showed that YY1 could decrease GHITM level via binding to its promoter. Taken together, our study revealed that GHITM was a promising therapeutic target for KIRC, which could modulate malignant phenotype and sensitivity to PD‐1 blockade of renal cancer cells via Notch signalling pathway. [ABSTRACT FROM AUTHOR]

Background: IL‐17A and TNF synergistically promote inflammation and tumorigenesis. Their interplay and impact on ovarian carcinoma (OC) progression are, however, poorly understood. We addressed this question focusing on mesothelial cells, whose interaction with tumor cells is known to play a pivotal role in transcoelomic metastasis formation. Methods: Flow‐cytometry and immunohistochemistry experiments were employed to identify cellular sources of IL‐17A and TNF. Changes in transcriptomes and secretomes were determined by bulk and single cell RNA sequencing as well as affinity proteomics. Functional consequences were investigated by microscopic analyses and tumor cell adhesion assays. Potential clinical implications were assessed by immunohistochemistry and survival analyses. Results: We identified Th17 cells as the main population of IL‐17A‐ and TNF producers in ascites and detected their accumulation in early omental metastases. Both IL‐17A and its receptor subunit IL‐17RC were associated with short survival of OC patients, pointing to a role in clinical progression. IL‐17A and TNF synergistically induced the reprogramming of mesothelial cells towards a pro‐inflammatory mesenchymal phenotype, concomitantly with a loss of tight junctions and an impairment of mesothelial monolayer integrity, thereby promoting cancer cell adhesion. IL‐17A and TNF synergistically induced the Th17‐promoting cytokines IL‐6 and IL‐1β as well as the Th17‐attracting chemokine CCL20 in mesothelial cells, indicating a reciprocal crosstalk that potentiates the tumor‐promoting role of Th17 cells in OC. Conclusions: Our findings reveal a novel function for Th17 cells in the OC microenvironment, which entails the IL‐17A/TNF‐mediated induction of mesothelial‐mesenchymal transition, disruption of mesothelial layer integrity and consequently promotion of OC cell adhesion. These effects are potentiated by a positive feedback loop between mesothelial and Th17 cells. Together with the observed clinical associations and accumulation of Th17 cells in omental micrometastases, our observations point to a potential role in early metastases formation and thus to new therapeutic options. [ABSTRACT FROM AUTHOR]

Drug resistance is perhaps the greatest obstacle in improving outcomes for cancer patients, leading to recurrence, progression and metastasis of various cancers. Exploring the underlying mechanism worth further study. N6‐methyladenosine (m6A) is the most common RNA modification found in eukaryotes, playing a vital role in RNA translation, transportation, stability, degradation, splicing and processing. Long noncoding RNA (lncRNA) refers to a group of transcripts that are longer than 200 nucleotides (nt) and typically lack the ability to code for proteins. LncRNA has been identified to play a significant role in regulating multiple aspects of tumour development and progression, including proliferation, metastasis, metabolism, and resistance to treatment. In recent years, a growing body of evidence has emerged, highlighting the crucial role of the interplay between m6A modification and lncRNA in determining the sensitivity of cancer cells to chemotherapeutic agents. In this review, we focus on the recent advancements in the interaction between m6A modification and lncRNA in the modulation of cancer drug resistance. Additionally, we aim to explore the underlying mechanisms involved in this process. The objective of this review is to provide valuable insights and suggest potential future directions for the reversal of chemoresistance in cancer. [ABSTRACT FROM AUTHOR]

Bladder cancer (BCa) is one of the common malignancies. Circular RNAs (circRNAs) play regulatory roles in cancer progression. CircITGA7 is a circRNA generated from several exons of ITGA7. The potential role of circITGA7 in BCa remains unknown and needs to be explored. Quantitative real time polymerase chain reaction (qRT‐PCR) was used to assess circITGA7 and miR‐330‐3p expression in BCa tissues and cell lines. Kaplan–Meier analysis was used to evaluate the overall survival of these BCa patients. The biological function of circITGA7 was examined by overexpression of circITGA7 using CCK‐8, EdU, wound‐healing, and Transwell assays. Xenograft assay was performed to further validate the in vitro results. To explore the mechanism of circITGA7, luciferase reporter, RNA pull‐down, fluorescence in situ hybridization (FISH) assays were employed to examine the binding interaction among circITGA7, miR‐330‐3p and kruppel‐like factor 10 (KLF10). Western blot was used to study the protein levels of KLF10.CircITGA7 was downregulated in BCa tissues and cell lines and indicated longer overall survival. Moreover, circITGA7 restricted cell proliferation, migration and invasion of BCa through negatively regulating miR‐330‐3p. The in vivo model showed that circITGA7 influenced the tumor growth. Besides, the overexpression of miR‐330‐3p promoted cell progression by directly targeting KLF10. Mechanistically, circITGA7 inhibited BCa progression by activating KLF10 via targeting miR‐330‐3p.CircITGA7 alleviates BCa cell progression via circITGA7/hsa‐miR‐330‐3p/KLF10 axis, which may provide novel therapeutic targets for BCa. [ABSTRACT FROM AUTHOR]

The peptide mimetic, NC114, is a promising anticancer compound that specifically kills colorectal cancer cells without affecting normal colon epithelial cells. In our previous study, we observed that NC114 inhibited the Wnt/β‐catenin pathway, with significant downregulation of both Ser 675‐phosphorylated β‐catenin and its target genes, cyclin D1 and survivin. However, the molecular mechanism responsible for its cytotoxic effect has not yet been fully characterized. In the present study, we demonstrated that NC114 prevented cell cycle progression from S to G2/M phase by downregulating cell cycle‐related gene expression, and also induced growth arrest in SW480 and HCT‐116 colorectal cancer cells. A novel covariation network analysis combined with transcriptome analysis revealed a series of signaling cascades affected by NC114 treatment, and identified protein kinase C‐δ (PKCδ) and forkhead box protein M1 (FOXM1) as important regulatory factors for NC114‐induced growth arrest. NC114 treatment inhibits the activation of PKCδ and its kinase activity, which suppresses MEK/ERK signaling. Attenuated MEK/ERK signaling then results in a reduction in FOXM1 phosphorylation and subsequent nuclear translocation of FOXM1 and β‐catenin. Consequently, formation of a T‐cell factor‐4 (TCF4)/β‐catenin transcription complex in the nucleus is inhibited and transcription of its target genes, such as cell cycle‐related genes, is downregulated. The efficacy of NC114 on tumor growth was confirmed in a xenograft model. Collectively, elucidation of the mechanism by which NC114 induces growth arrest in colorectal cancer cells should provide a novel therapeutic strategy for colorectal cancer treatment. [ABSTRACT FROM AUTHOR]

Heightened lactate production in cancer cells has been linked to various cellular mechanisms such as angiogenesis, hypoxia, macrophage polarisation and T‐cell dysfunction. The lactate‐induced lactylation of histone lysine residues is noteworthy, as it functions as an epigenetic modification that directly augments gene transcription from chromatin. This epigenetic modification originating from lactate effectively fosters a reliance on transcription, thereby expediting tumour progression and development. Herein, this review explores the correlation between histone lactylation and cancer characteristics, revealing histone lactylation as an innovative epigenetic process that enhances the vulnerability of cells to malignancy. Moreover, it is imperative to acknowledge the paramount importance of acknowledging innovative therapeutic methodologies for proficiently managing cancer by precisely targeting lactate signalling. This comprehensive review illuminates a crucial yet inadequately investigated aspect of histone lactylation, providing valuable insights into its clinical ramifications and prospective therapeutic interventions centred on lactylation. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitors (TKIs) are routinely prescribed for the treatment of non‐small cell lung cancer (NSCLC). As with all medications, patients can experience adverse events due to TKIs. Unfortunately, the relationship between many TKIs and the occurrence of certain adverse events remains unclear. There are limited in vivo studies which focus on TKIs and their effects on different regulation pathways. Many in vitro studies, however, that investigate the effects of TKIs observe additional changes, such as changes in gene activations or protein expressions. These studies could potentially help to gain greater understanding of the mechanisms for TKI induced adverse events. However, in order to utilize these pathways in a pharmacokinetic/pharmacodynamic (PK/PD) framework, an in vitro PK/PD model needs to be developed, in order to characterize the effects of TKIs in NSCLC cell lines. Through the use of ordinary differential equations, cell viability data and nonlinear mixed effects modeling, an in vitro TKI PK/PD model was developed with estimated PK and PD parameter values for the TKIs alectinib, crizotinib, erlotinib, and gefitinib. The relative standard errors for the population parameters are all less than 25%. The inclusion of random effects enabled the model to predict individual parameter values which provided a closer fit to the observed response. It is hoped that this model can be extended to include in vitro data of certain pathways that may potentially be linked with adverse events and provide a better understanding of TKI‐induced adverse events. [ABSTRACT FROM AUTHOR]

Many mouse models of neoplasia and pre-neoplasia require the examination of whole mounts of the gastrointestinal tract. A simple device has been produced to facilitate the rapid preparation of mouse intestines for subsequent quantification of tumours and pre-neoplastic lesions such as aberrant crypt foci. The device greatly speeds up the production of whole mounts and also provides far more consistent and better-quality preparations. [ABSTRACT FROM AUTHOR]

Summary: There have been substantial strides forward in our understanding of the contribution of regulatory T (Treg) cells to cancer immunosuppression. In this issue, we present a series of papers highlighting emerging themes on this topic relevant not only to our understanding of the fundamental biology of tumour immunosuppression but also to the design of new immunotherapeutic approaches. The substantially shared biology of CD4+ conventional T (Tconv) and Treg cells necessitates a detailed understanding of the potentially opposing functional consequences that immunotherapies will have on Treg and Tconv cells, a prominent example being the potential for Treg‐mediated hyperprogressive disease following anti‐PD‐1 therapy. Such understanding will aid patient stratification and the rational design of combination therapies. It is also becoming clear, however, that Treg cells within tumours exhibit distinct biological features to both Tconv cells and Treg cells in other tissues. These distinct features provide the opportunity for development of targeted immunotherapies with greater efficacy and reduced potential for inducing systemic toxicity. [ABSTRACT FROM AUTHOR]

The paper describes further characterization of the 55-kDa short-chain collagen from lens capsule. Lens capsules were extracted with 5.5 M guanidine · HCl and the extracted material was fractionated on agarose A5M followed by high-pressure liquid chromatography (HPLC). By amino acid composition, the major fraction obtained from HPLC was found to be different than type-IV collagen fragments. The 55-kDa short-chain collagen on pepsin digestion produced a 45-kDa pepsin-resistant fragment. The undifferentiated embryonal carcinoma (F-9) cells were found to synthesize increased amounts of 55-kDa short-chain collagen. The identity of this biosynthesized molecule with 55-kDa short-chain collagen from lens capsules was established by immunoprecipitation experiments. The results indicated a close similarity or identical nature of the short-chain collagens from these two sources. [ABSTRACT FROM AUTHOR]

Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single‐cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA‐seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high‐throughput and high‐sensitivity method called snHH‐seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full‐length RNA‐seq data is also established. snHH‐seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan‐cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full‐length RNA at the single‐nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology. [ABSTRACT FROM AUTHOR]

Tumour cell dormancy is critical for metastasis and resistance to chemoradiotherapy. Polyploid giant cancer cells (PGCCs) with giant or multiple nuclei and high DNA content have the properties of cancer stem cell and single PGCCs can individually generate tumours in immunodeficient mice. PGCCs represent a dormant form of cancer cells that survive harsh tumour conditions and contribute to tumour recurrence. Hypoxic mimics, chemotherapeutics, radiation and cytotoxic traditional Chinese medicines can induce PGCCs formation through endoreduplication and/or cell fusion. After incubation, dormant PGCCs can recover from the treatment and produce daughter cells with strong proliferative, migratory and invasive abilities via asymmetric cell division. Additionally, PGCCs can resist hypoxia or chemical stress and have a distinct protein signature that involves chromatin remodelling and cell cycle regulation. Dormant PGCCs form the cellular basis for therapeutic resistance, metastatic cascade and disease recurrence. This review summarises regulatory mechanisms governing dormant cancer cells entry and exit of dormancy, which may be used by PGCCs, and potential therapeutic strategies for targeting PGCCs. [ABSTRACT FROM AUTHOR]

Purpose: To observe the inhibitory effect of the small molecule tyrosine kinase inhibitor apatinib on small cell lung cancer in vitro and vivo. Material and methods: Three small lung cancer cells were selected CCK‐8 and monoclonal assay was used to determine the effect of apatinib on proliferation. The effects on cell cycle and apoptosis were detected by flow cytometry and TUNEL. We observed the inhibitory effect of different doses of apatinib on xenograft tumor. The efficacy and safety of apatinib in 20 patients with advanced small cell lung cancer were observed. Results: For small cell lung cancer with high expression of VEGFR2, apatinib has a significant inhibitory effect both in vitro and in vivo. It can play an inhibitory role by promoting apoptosis and cell cycle arrest pathways. For small cell lung cancer with low expression of VEGFR, the inhibitory effect on cells in vitro was not significant. It has certain inhibitory effect on nude mouse transplanted tumor and small cell lung cancer patients, but the effect is weaker than that of animal models and patients with small cell lung cancer cells with high expression of VEGFR2. Conclusion: Apatinib has a significant inhibitory effect on small cell lung cancer with high expression of VEGFR2 and may be a treatment for small cell lung cancer patients. [ABSTRACT FROM AUTHOR]

Most living organisms secrete tiny lipid bilayer particles encapsulating various biomolecular entities, including nucleic acids and proteins. These secreted extracellular vesicles (EVs) are shown to aid in communication between cells and their environment. EVs are mainly involved in the signalling and manipulation of physiological processes. Plant EVs display similar functional activity as seen in mammalian EVs. Medicinal plants have many bioactive constituents with potential applications in cancer treatment. Particularly, Basil (Ocimum basilicum), has wide therapeutic properties including anti‐inflammatory, anti‐cancer, and anti‐infection, among others. In this study, we focused on using EVs purified from Apoplast Washing Fluid (AWF) of Basil plant leaves as a biological therapeutic agent against cancer. Characterization of Basil EVs revealed a size range of 100–250 nm, which were later assessed for their cell uptake and apoptosis inducing abilities in pancreatic cancer cells. Basil plant EVs (BasEVs) showed a significant cytotoxic effect on pancreatic cancer cell line MIA PaCa‐2 at a concentration of 80 and 160 μg/mL in cell viability, as well as clonogenic assays. Similarly, RT‐PCR and western blot analysis has shown up regulation in apoptotic gene and protein expression of Bax, respectively, in BasEV treatment groups compared to untreated controls of MIA PaCa‐2. Overall, our results suggest that EVs from basil plants have potent anti‐cancer effects in pancreatic cancer cells and can serve as a drug delivery system, demanding an investigation into the therapeutic potential of other medicinal plant EVs. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC), which accounts for 90% of all oral cancers, has become a public health crisis worldwide. despite advances in therapeutic interventions, the prognosis remains poor for advanced‐stage OSCC. In this study, we investigate the anticancer activity and the mode of action of hellebrigenin in human OSCC. The findings demonstrated that hellebrigenin exerted cytotoxic effects in OSCC cells through cell cycle arrest at the G2/M phase and downregulation of cell cycle‐related proteins (cyclins A2, B1 and D3, Cdc2, CDK4 and CDK6). Moreover, hellebrigenin caused activation of PARP and caspase 3, 8 and 9, followed by downregulation of antiapoptotic proteins (Bcl‐2 and Bcl‐xL) and upregulation of pro‐apoptotic proteins (Bax and Bak). The hellebrigenin treatment also increased Fas, DR5, DcR2 and DcR3 expressions in oral cancer cells, indicating the compound causes oral cancer cell apoptosis through both intrinsic and extrinsic pathways. Regarding upstream signalling, hellebrigenin was found to reduce the phosphorylation of ERK, p38, and JNK, indicating that hellebrigenin triggers caspase‐mediated apoptosis by downregulating MAPK signalling pathway. Finally, the human apoptosis array findings revealed that hellebrigenin specifically suppressed the expression of XIAP to execute its pro‐apoptotic activities. Taken together, the study suggests that hellebrigenin can act as a potent anticancer compound in human OSCC. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC), known as prevalent cancer, has risen to be the leading cause of cancer-related death. Engineered exosomes had attracted much attention since they acted as carriers to deliver small molecule drugs, therapeutic nucleic acids, and polypeptides to treat a series of cancers. Methods and Results: Here, we found that the PKH-26 labeled exosomes, which were derived from the CRC cells, could be efficiently absorbed by SW1116 cells and had an abundant fluorescence distribution in tumors, compared with the exosomes derived from mesenchymal stem cells (MSC) and HepG2 cells. This Research demonstrated that engineered CRC-exosomes loaded with functional miR-1270 (Exo-miR-1270) enriched in miR-1270 strongly inhibited the proliferation by CCK-8 and EdU assays, migration by wound-healing and transwell assays, and promoted the apoptosis for CRC cells through flow cytometry. MiR1270 overexpression delivered by CRC exosomes contributed to inhibiting the tumor growth potential of CRC in vivo and increasing the overall survival of the mice. Moreover, the safety evaluation results showed that CRC-exosomes loaded with functional miR-1270-mimics had no toxicity for other organs by histopathological analysis and no influence on the vital chemistry and hematology parameters for mice in vivo safety evaluation. Conclusion: These results indicate that Exo-miR-1270 can effectively treat CRC tumors by intravenous administration. Our work provided a foundation that the homologous tumor-derived exosomes mediated miRNA delivery for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Background: Myeloid-derived suppressor cells (MDSCs) played an essential role in tumor microenvironment to suppress host antitumor immunity and help cancer cells escape immune surveillance. However, the molecular mechanism behind tumor evasion mediated by MDSCs is not fully understood. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is considered to associate with tumor initiation, metastasis and angiogenesis. Blocking GPNMB function is a potentially valuable therapy for cancer by eliminating GPNMB+MDSCs. Our previous study has proved that blockage the MyD88 signaling with the MyD88 inhibitor, TJ-M2010-5, may completely prevent the development of CAC in mice, accompanying with downregulation of GPNMB mRNA in the inhibitor-treated mice of CAC. Methods: We here focus on the underlying the relationship between GPNMB function and MyD88 signaling pathway activation in MDSCs' antitumor activity in CAC. Results: CAC development in the mouse model is associated with expanded GPNMB+MDSCs by a MyD88-dependent pathway. The GPNMB expression on MDSCs is associated with MyD88 signaling activation. The inhibitory effect of MDSCs on T cell proliferation, activation and antitumor cytotoxicity in CAC is mediated by GPNMB in a MyD8-dependent manner. Conclusion: MyD88 signaling pathway plays an essential role in GPNMB+MDSCmediated tumor immune escape during CAC development and is a promising focus for revealing the mechanisms of MDSC that facilitate immunosuppression and tumor progression. [ABSTRACT FROM AUTHOR]

The complex interplay between tumour cells and the tumour microenvironment (TME) underscores the necessity for gaining comprehensive insights into disease progression. This study centres on elucidating the elusive the elusive role of endothelial cells within the TME of head and neck squamous cell carcinoma (HNSCC). Despite their crucial involvement in angiogenesis and vascular function, the mechanistic diversity of endothelial cells among HNSCC patients remains largely uncharted. Leveraging advanced single‐cell RNA sequencing (scRNA‐Seq) technology and the Scissor algorithm, we aimed to bridge this knowledge gap and illuminate the intricate interplay between endothelial cells and patient prognosis within the context of HNSCC. Here, endothelial cells were categorized into Scissorhigh and Scissorlow subtypes. We identified Scissor+ endothelial cells exhibiting pro‐tumorigenic profiles and constructed a prognostic risk model for HNSCC. Additionally, four biomarkers also were identified by analysing the gene expression profiles of patients with HNSCC and a prognostic risk prediction model was constructed based on these genes. Furthermore, the correlations between endothelial cells and prognosis of patients with HNSCC were analysed by integrating bulk and single‐cell sequencing data, revealing a close association between SHSS and the overall survival (OS) of HNSCC patients with malignant endothelial cells. Finally, we validated the prognostic model by RT‐qPCR and IHC analysis. These findings enhance our comprehension of TME heterogeneity at the single‐cell level and provide a prognostic model for HNSCC. [ABSTRACT FROM AUTHOR]

Aims: Tumor‐associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the mechanism remains incompletely inventoried. The focus of this study was to investigate the distinctions of M2‐like TAMs in the immune microenvironment between primary and recurrent malignant glioma and its influence in the recurrence. Methods: We employed single‐cell RNA sequencing to construct a single‐cell atlas for a total of 23,010 individual cells from 6 patients with primary or recurrent malignant glioma and identified 5 cell types, including TAMs and malignant cells. Immunohistochemical techniques and proteomics analysis were performed to investigate the role of intercellular interaction between malignant cells and TAMs in the recurrence of malignant glioma. Results: Six subgroups of TAMs were annotated and M2‐like TAMs were found to increase in recurrent malignant glioma significantly. A pseudotime trajectory and a dynamic gene expression profiling during the recurrence of malignant glioma were reconstructed. Up‐regulation of several cancer pathways and intercellular interaction‐related genes are associated with the recurrence of malignant glioma. Moreover, the M2‐like TAMs can activate the PI3K/Akt/HIF‐1α/CA9 pathway in the malignant glioma cells via SPP1‐CD44‐mediated intercellular interaction. Interestingly, high expression of CA9 can trigger the immunosuppressive response in the malignant glioma, thus promoting the degree of malignancy and drug resistance. Conclusion: Our study uncovers the distinction of M2‐like TAMs between primary and recurrent glioma, which offers unparalleled insights into the immune microenvironment of primary and recurrent malignant glioma. [ABSTRACT FROM AUTHOR]

Despite the growing appreciation that the future of cancer treatment lies in combination therapies, finding the right drugs to combine and the optimal way to combine them remains a nontrivial task. Herein, we introduce the Multi‐Objective Optimization of Combination Synergy – Dose Selection (MOOCS‐DS) method for using drug synergy as a tool for guiding dose selection for a combination of preselected compounds. This method decouples synergy of potency (SoP) and synergy of efficacy (SoE) and identifies Pareto optimal solutions in a multi‐objective synergy space. Using a toy combination therapy model, we explore properties of the MOOCS‐DS algorithm, including how optimal dose selection can be influenced by the metric used to define SoP and SoE. We also demonstrate the potential of our approach to guide dose and schedule selection using a model fit to preclinical data of the combination of the PD‐1 checkpoint inhibitor pembrolizumab and the anti‐angiogenic drug bevacizumab on two lung cancer cell lines. The identification of optimally synergistic combination doses has the potential to inform preclinical experimental design and improve the success rates of combination therapies. Jel classificationDose Finding in Oncology [ABSTRACT FROM AUTHOR]

Laetiporus sulphureus (Bull.) Murrill is a well‐known edible mushroom consumed in nutrition as delicacy. It has been used in traditional medicine because of its beneficial effects on human wellness, such as antimicrobial, antioxidant, and anticancer potential. The present study determined the phenolic profile of Laetiporus sulphureus ethanolic extract (LSE) by high‐performance liquid chromatographic method. Tolerance of two probiotic bacterial strains Lactiplantibacillus plantarum 229v, Bifidobacterium animalis subsp. lactis and probiotic yeast Saccharomyces boulardii on LSE was analyzed in terms of viability and biofilm formation. Effects of extract on colorectal (HCT‐116) and cervical (HeLa) cancer cells viability was determined using MTT test in concentration range: 1–500 μg/mL after 24 and 72 h. Redox parameters (superoxide anion radicals, nitrites, and reduced glutathione) were evaluated using NBT, Griess, and GSH assays in the concentration range of 1–500 μg/mL after 24 and 72 h. Antimigratory activity was determined by wound healing method using selected concentrations of 10 and 50 μg/mL after 24 h. Untreated cells were considered as control. As control cell line, we used healthy fibroblasts (MRC‐5). Our results demonstrated abundance of LSE in phenolics, with rosmarinic acid as the main component. LSE induced low tolerance of tested planktonic probiotic strains, with no affection on their ability to form biofilm. No significant cytotoxicity on tested cancer cells was observed, with prooxidative and antimigratory effects noticed. Extract exerted significant antimigratory activity on cancer cells without effect on planktonic and probiotic cultures in biofilm. These results indicate potential application of Laetiporus sulphureus ethanolic extract as natural protector of probiotics with prominent ability to suppress cancer cell motility. [ABSTRACT FROM AUTHOR]

Associations between plasma membrane blebbing and metastatic progression have been widely reported. There are also reports of increased extracellular vesicle (EV) release from cancer cells. Yet the ties between these closely related phenomena are incompletely understood. In this commentary, we remark on a recent finding on cellular membrane blebs in melanoma signalling. We discuss possible implications for cancer biology and draw parallels to knowns and unknowns in the relationships of EVs and cancer progression. [ABSTRACT FROM AUTHOR]

Hydrogen sulphide (H2S) is a gaseous neurotransmitter that can be self‐synthesized by living organisms. With the deepening of research, the pathophysiological mechanisms of endogenous H2S in cancer have been increasingly elucidated: (1) promote angiogenesis, (2) stimulate cell bioenergetics, (3) promote migration and proliferation thereby invasion, (4) inhibit apoptosis and (5) activate abnormal cell cycle. However, the increasing H2S levels via exogenous sources show the opposite trend. This phenomenon can be explained by the bell‐shaped pharmacological model of H2S, that is, the production of endogenous (low concentration) H2S promotes tumour growth while the exogenous (high concentration) H2S inhibits tumour growth. Here, we review the impact of endogenous H2S synthesis and metabolism on tumour progression, summarize the mechanism of action of H2S in tumour growth, and discuss the possibility of H2S as a potential target for tumour treatment. [ABSTRACT FROM AUTHOR]

Cancer cell plasticity is the ability of tumor cells to switch phenotypes and is one of the predominant requisites of cancer cells capable of undergoing metastasis. Cancer cell plasticity is also recognized as one of the major contributors to intratumoral heterogeneity, a critical factor underlying the progression of malignant tumors, which is known to modify tumor response and induce resistance against various modes of therapy, thus posing a barrier to efficient cancer management. Cancer cell plasticity is acquired by the subversion of cell signaling pathways like mitogen‐activated protein kinase pathway, phosphoinositide‐3‐kinase, signal transducer and activator of transcription 3, Wnt, Hedgehog and Notch as well as cellular programs such as epithelial to mesenchymal transition and phenotypic plasticity. This complex phenomenon has been studied in many cancer types like pancreatic cancer, colon cancer and breast cancer. This review will explore the current understanding we have in breast cancer on the intrinsic molecular mechanisms of cancer cell plasticity and the resistance to various types of cancer therapy that arise as a result of plasticity. We conclude by exploring the potential novel therapies that specifically target the pathways leading to plasticity and can be leveraged to treat patients living with the disease. [ABSTRACT FROM AUTHOR]

In this special interview series, we profile members of TheFEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Hyunsook Lee is Professor at the Laboratory of Cancer Cell Biology at Seoul National University in Korea. She has served as an editorial board member of TheFEBS Journal since 2018. [ABSTRACT FROM AUTHOR]

Recent studies revealed a new biological process that malignant cancer cells hijack mitochondria from nearby T cells, providing another potential mechanism for immune evasion. We further confirmed this process at the single‐cell genomic level through MERCI, a novel algorithm for tracking mitochondrial (MT) transfer. Applied to human cancer samples, MERCI identified a new cancer phenotype linked to MT hijacking, correlating with rapid tumour proliferation and poor patient survival. This discovery offers insights into the limitations of current cancer immunotherapies and suggests new therapeutic avenues targeting MT transfer to enhance cancer treatment efficacy. [ABSTRACT FROM AUTHOR]

The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science. [ABSTRACT FROM AUTHOR]

Ruk/CIN85 is an adaptor protein. Similar to many other proteins of this type, Ruk/CIN85 is known to take part in multiple cellular processes including signal transduction, vesicle-mediated transport, cytoskeleton remodelling, programmed cell death and viral infection. Recent studies have also revealed the potential importance of Ruk/CIN85 in cancer cell invasiveness. In this review we summarize the various roles of this protein as well as the potential contribution of Ruk/CIN85 to malignancy and the invasiveness of cancer cells. In the last section of the paper we also speculate on the utility of Ruk/CIN85 as a target for novel anti-cancer therapies. [ABSTRACT FROM AUTHOR]

Acidic extracellular pH (pHe) has been shown to stimulate peripheral lysosome trafficking, resulting in cathepsin B secretion and tumor invasion. In addition, inhibitors of sodium-proton exchangers (NHE) such as EIPA, cariporide and s3226, as well as the non-specific NHE inhibitor, troglitazone (Tro), blocked these changes. In this paper, we report a differential ability of the thiazolidinedione (TZD) family of compounds to induce a time-dependent retrograde aggregation of lysosomes over the microtubule-organizing center (MTOC) in tumor cells exposed to acidic pHe. This trafficking event depended on microtubules and the MAP-Kinase pathway, but was independent of Rho GTPase activity. Expression of shRNA implicated Rab7 in this process, and subcellular fractionation revealed that levels of Rab7, RILP and Erk1/2 were increased on lysosomes purified from cells treated with Tro. In addition, DN-RILP overexpression studies indicated that this Rab7 effector also played a role in TZD-induced retrograde trafficking. Tro was able to prevent acidic pHe-induced cell invasion. Finally, DU145 prostate tumor cells stably over-expressing WT-RILP, a condition where lysosomes aggregate to the MTOC in the absence of Tro, did not invade in response to acidic pHe, suggesting that the regulation of lysosome trafficking is an inherently important aspect of tumor cell invasion. [ABSTRACT FROM AUTHOR]

The classification problem consists of using some known objects, usually described by a large vector of features, to induce a model that classifies others into known classes. Feature selection is widely used as the first stage of the classification task to reduce the dimension of the problem, decrease noise and improve speed by the elimination of irrelevant or redundant features. The present paper deals with the optimization of nearest neighbour classifiers via intelligent and nature inspired algorithms for a very significant medical problem, the Pap smear cell classification problem. The algorithms used include tabu search, genetic algorithms, particle swarm optimization and ant colony optimization. The proposed complete algorithmic scheme is tested on two sets of data. The first consists of 917 images of Pap smear cells and the second set consists of 500 images, classified carefully by expert cyto-technicians and doctors. Each cell is described by 20 numerical features, and the cells fall into seven classes representing a variety of normal and abnormal cases. Nevertheless, from the medical diagnosis viewpoint, a minimum requirement corresponds to the general two-class problem of correct separation between normal and abnormal cells. [ABSTRACT FROM AUTHOR]