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Objective: The main objective of this comprehensive mixed-methods investigation conducted in Jordan were to explore and understand men's engagement in cancer screening., Methods: The research employed a mixed-methods approach, combining a survey with 209 participants and focus group interviews with 30 individuals. The survey involved quantitative data collection methods to gather information on cancer screening participation rates among men in Amman. Focus group interviews were conducted to collect qualitative data on the factors influencing cancer screening utilization among men in Amman., Results: The study revealed a notably low participation rate, with less than 37% of men engaging in cancer screening. The diminished involvement was attributed to several factors, including health illiteracy, language barriers, restricted access to health-related information and screening services, and cultural considerations., Conclusions: Based on the findings, the research strongly advocates for tailored interventions that are culturally specific. The emphasis is on the importance of training community health workers to address the identified challenges and enhance both cancer prevention awareness and screening accessibility in Jordan.

Cancer is a group of diseases marked by unchecked cell proliferation and the ability for the disease to metastasize to different body areas. Enhancements in treatment and early detection are crucial for improved outcomes. LncRNAs are RNA molecules that encode proteins and have a length of more than 200 nucleotides. LncRNAs are crucial for chromatin architecture, gene regulation, and other cellular activities that impact both normal growth & pathological processes, even though they are unable to code for proteins. LncRNAs have emerged as significant regulators in the study of cancer biology, with a focus on their intricate function in the Notch signaling pathway. The imbalance of this pathway is often linked to a variety of malignancies. Notch signaling is essential for cellular functions like proliferation, differentiation, and death. The cellular response is shaped by these lncRNAs through their modulation of essential Notch pathway constituents such as receptors, ligands, and downstream effectors around it. Furthermore, a variety of cancer types exhibit irregular expression of Notch-related lncRNAs, underscoring their potential use as therapeutic targets and diagnostic markers. Gaining an understanding of the molecular processes behind the interaction between the Notch pathway and lncRNAs will help you better understand the intricate regulatory networks that control the development of cancer. This can open up new possibilities for individualized treatment plans and focused therapeutic interventions. The intricate relationships between lncRNAs & the Notch pathway in cancer are examined in this review., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: This study aimed to explore the relationship between depressive symptoms and demographic as well as health-related variables in elderly individuals diagnosed with cancer., Methods: A cohort of 50 elderly cancer patients participated in the study. Data collection involved the completion of surveys and assessments encompassing demographic characteristics, medical profiles, levels of depression, cognitive functioning, activities of daily living, and perceived social support., Results: Findings revealed that among the elderly participants, 45% experienced mild depression, 20% exhibited moderate depression, and 5% showed severe depression. Depression levels were found to be linked to marital status (P = 0.03), with widowed individuals reporting the highest depression rates (80%) and single individuals reporting the lowest (4%). Living arrangements were significantly associated with depression (P = 0.012), with participants cohabiting with their partner and children showing lower depression rates (6%) compared to those living solely with their children (40%). Additionally, depression showed a significant correlation with income (P = 0.01), as individuals reporting insufficient income for living expenses displayed higher levels of depression (58%). Furthermore, depression was notably linked to chronic health conditions like diabetes and respiratory ailments (P = .023), with individuals grappling with respiratory issues reporting the highest depression scores., Conclusion: Recognizing and addressing factors such as marital status, living situation, income level, and the presence of chronic illnesses hold the potential for healthcare professionals to tailor interventions effectively to meet the specific requirements of this vulnerable demographic. This tailored approach has the capability to contribute significantly to enhancing the overall well-being and mental health outcomes of elderly cancer patients.

The large-scale collections, screening and discovery of biologically active and pharmacologically significant marine-derived natural products have garnered tremendous attraction. Edible brown algae are rich in fucoidan. Importantly, fucoidan has been reported to inhibit carcinogenesis and metastasis mainly through the regulation of deregulated cell signaling pathways. This review summarizes the structural features of fucoidan, including monosaccharide type, sulfate content, and main chain structure. We have set spotlight on fucoidan-mediated tumor suppressive effects in cell cultures studies and tumor-bearing rodent models. Fucoidan exerts anti-tumor effects primarily through the inhibition of tumor cell viability, proliferation and metastatic dissemination of cancer cells from primary tumor sites to distant secondary sites. Fucoidan not only promotes immunological responses in tumor microenvironment but also induces apoptotic death in cancer cells. In addition, fucoidan can be used as a dietary supplement for preventive purposes, in combination with other drugs as complementary and alternative medicine or with nanoparticle modifications will be the future of fucoidan use. Cutting-edge research related to fucoidan has catalyzed the transition of fucoidan from preclinical studies to different phases of clinical trials. Rationally designed clinical trials for the critical evaluation of fucoidan against different cancers will be valuable to reap full benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Cancer is a complex disease that causes abnormal genetic changes and unchecked cellular growth. It also causes a disruption in the normal regulatory processes that leads to the creation of malignant tissue. The complex interplay of genetic, environmental, and epigenetic variables influences its etiology. Long non-coding RNAs (LncRNAs) have emerged as pivotal contributors within the intricate landscape of cancer biology, orchestrating an array of multifaceted cellular processes that substantiate the processes of carcinogenesis and metastasis. Metastasis is a crucial driver of cancer mortality. Among these, MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) has drawn a lot of interest for its function in encouraging metastasis via controlling the Epithelial-Mesenchymal Transition (EMT) procedure. MALAT1 exerts a pivotal influence on the process of EMT, thereby promoting metastasis to distant organs. The mechanistic underpinning of this phenomenon involves the orchestration of an intricate regulatory network encompassing transcription factors, signalling cascades, and genes intricately associated with the EMT process by MALAT1. Its crucial function in transforming tumor cells into an aggressive phenotype is highlighted by its capacity to influence the expression of essential EMT effectors such as N-cadherin, E-cadherin, and Snail. An understanding of the MALAT1-EMT axis provides potential therapeutic approaches for cancer intervention. Targeting MALAT1 or its downstream EMT effectors may reduce the spread of metastatic disease and improve the effectiveness of already available therapies. Understanding the MALAT1-EMT axis holds significant clinical implications. Therefore, directing attention towards MALAT1 or its downstream mediators could present innovative therapeutic strategies for mitigating metastasis and improving patient prognosis. This study highlights the importance of MALAT1 in cancer biology and its potential for cutting back on metastatic disease with novel treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The intricate molecular pathways governing cancer development and progression have spurred intensive investigations into novel therapeutic targets. Glycogen Synthase Kinase-3 (GSK3), a complex serine/threonine kinase, has emerged as a key player with intricate roles in various cellular processes, including cell proliferation, differentiation, apoptosis, and metabolism. Harnessing GSK3 inhibitors as potential candidates for cancer therapy has garnered significant interest due to their ability to modulate key signalling pathways that drive oncogenesis. The review encompasses a thorough examination of the molecular mechanisms underlying GSK3's involvement in cancer progression, shedding light on its interaction with critical pathways such as Wnt/β-catenin, PI3K/AKT, and NF-κB. Through these interactions, GSK3 exerts influence over tumour growth, invasion, angiogenesis, and metastasis, rendering it an attractive target for therapeutic intervention. The discussion includes preclinical and clinical studies, showcasing the inhibitors efficacy across a spectrum of cancer types, including pancreatic, ovarian, lung, and other malignancies. Insights from recent studies highlight the potential synergistic effects of combining GSK3 inhibitors with conventional chemotherapeutic agents or targeted therapies, opening avenues for innovative combinatorial approaches. This review provides a comprehensive overview of the current state of research surrounding GSK3 inhibitors as promising agents for cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Platelet-Derived Growth Factor (PDGF) mediated signaling has emerged as one of the most extensively studied cascades in cancer development and progression. Overwhelmingly increasing data obtained from preclinical and clinical studies has helped us to develop a near-complete resolution of PDGF/PDGFR signaling landscape. Phenotype- and genotype-driven studies have provided proof-of-concept that therapeutic targeting of PDGF/PDGFR signaling axis is necessary to improve clinical outcome.   Kinase inhibitor drug discovery programmes have broadened their focus to include a wide variety of kinase targets. Based on the insights gleaned from previously published high-impact research, it is clear that different transduction cascades crosstalk with PDGF/PDGFR signaling during primary tumor invasion, dissemination and ultimate metastasis of cancer cells. In this commentary, we will focus on involvement of PDGF/PDGFR signaling in different cancers and how pharmacological targeting of this signaling cascade inhibits cancer progression.

The molecular mechanisms and signal transduction cascades evoked by the activation of aryl hydrocarbon receptor (AhR) are becoming increasingly understandable. AhR is a ligand-activated transcriptional factor that integrates environmental, dietary and metabolic cues for the pleiotropic regulation of a wide variety of mechanisms. AhR mediates transcriptional programming in a ligand-specific, context-specific and cell-type-specific manner. Pioneering cutting-edge research works have provided fascinating new insights into the mechanistic role of AhR-driven downstream signaling in a wide variety of cancers. AhR ligands derived from food, environmental contaminants and intestinal microbiota strategically activated AhR signaling and regulated multiple stages of cancer. Although AhR has classically been viewed and characterized as a ligand-regulated transcriptional factor, its role as a ubiquitin ligase is fascinating. Accordingly, recent evidence has paradigmatically shifted our understanding and urged researchers to drill down deep into these novel and clinically valuable facets of AhR biology. Our rapidly increasing realization related to AhR-mediated regulation of the ubiquitination and proteasomal degradation of different proteins has started to scratch the surface of intriguing mechanisms. Furthermore, AhR and epigenome dynamics have shown previously unprecedented complexity during multiple stages of cancer progression. AhR not only transcriptionally regulated epigenetic-associated molecules, but also worked with epigenetic-modifying enzymes during cancer progression. In this review, we have summarized the findings obtained not only from cell-culture studies, but also from animal models. Different clinical trials are currently being conducted using AhR inhibitors and PD-1 inhibitors (Pembrolizumab and nivolumab), which confirm the linchpin role of AhR-related mechanistic details in cancer progression. Therefore, further studies are required to develop a better comprehension of the many-sided and "diametrically opposed" roles of AhR in the regulation of carcinogenesis and metastatic spread of cancer cells to the secondary organs.

Cytotoxic drugs have long been recognised to kill cancer cells through apoptosis. According to a current study, pyroptosis inhibits cell proliferation and shrinks tumors. Pyroptosis and apoptosis are caspase-dependent programmed cell death (PCD) processes. Inflammasomes activate caspase-1 and latent cytokines, including IL-1β and IL-18, to cleave gasdermin E (GSDME) and induce pyroptosis. Gasdermin proteins activate caspase-3 to induce pyroptosis, which is associated with tumour genesis, development, and therapy response. These proteins may serve as therapeutic biomarkers for cancer detection, and their antagonists may be a new target. Caspase-3, a crucial protein in both pyroptosis and apoptosis, governs tumour cytotoxicity when activated, and GSDME expression modulates this. Once active caspase-3 cleaves GSDME, its N-terminal domain punches holes in the cell membrane, causing it to expand, burst, and die. To understand the cellular and molecular mechanisms of PCD mediated by caspase-3 and GSDME, we focused on pyroptosis. Hence, caspase-3 and GSDME may be promising targets for cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rutin is one of the flavonoids found in fruits and vegetables. The PI3K/AKT/mTOR signaling pathway is critical for the life cycle at the cellular level. In current study, we purposed to demonstrate the antitumoral effect of rutin at different doses through the mTOR-signaling pathway and argyrophilic nucleolar regulatory region. EAC cells were injected subcutaneously into the experimental groups. 25 and 50 mg/kg Rutin were injected intraperitoneally to the animals with solid tumors for 14 days. Immunohistochemical, Real-time PCR and AgNOR analyzes were actualized on the taken tumors. When the rutin given groups and the tumor group were compared, the tumor size increase was detected to be statistically significant (p < 0.05). In immunohistochemical analysis, a significant decrease was encountered in the AKT, mTOR, PI3K and F8 expressions especially in the groups administered 25 mg Rutin, in comparison with the control group (p < 0.05). AgNOR area/nuclear area (TAA/NA) and average AgNOR number were determineted, and statistically important differences were detected between the groups in terms of TAA/NA ratio (p < 0.05). There were significant statistical differences between the mRNA quantity of the PI3K, AKT1 and mTOR genes (p < 0.05). In the in vitro study, cell apoptosis was evaluated with different doses of annexin V and it was determined that a dose of 10 µg/mL Rutin induced apoptosis (p < 0.05). In our study, it was demonstrated in vivo and in vitro that Rutin has an anti-tumor effect on the development of solid tumors formed by both EAC cells., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Deciphering information hidden in the gene expression assays for identifying disease subtypes has significant importance in precision medicine. However, computational limitations thwart this process due to the intricacy of the biological networks and the curse of dimensionality of gene expression data. Therefore, clustering in such scenarios often becomes the first choice of exploratory data analysis to identify natural structures and intrinsic patterns in the data. However, sparse and high dimensional nature of omics data prevents conventional clustering algorithms to discover subtypes that are clinically relevant and statistically significant. Hence, non-linear dimensionality reduction techniques coupled with clustering in such scenarios often becomes imperative to improve the clustering results. In this study, we present a robust pipeline to discover disease subtypes with clinical relevance. Specifically, we focus on discovering patient sub-groups that have a residual life patterns remarkably different from other sub-groups. This is significant because by refining prognosis, subtyping can reduce uncertainty in approximating patients expected outcome. The methodology present is based on robust correlation estimation, UMAP- a non-linear dimensionality reduction method and mapper- a tool from topology. Notably, we suggest a method for improving the robustness of the correlation matrix of gene expression data for improving the clustering results. The performance of the model is evaluated by applying to five cancer datasets obtained through TCGA and comparisons are performed with some state of the art methods of NEMO, RSC-OTRI and SNF with regard to log-rank test and Restricted Life Expectancy Difference. For example in GBM dataset, the minimum separation for any two discovered subtypes is 221 days which is significantly higher than the other methodologies. We also compared the results without using the robust correlation based estimate and observed that robust correlation improves separability between survival curves significantly. From the results we infer that our methodology performs better compared to other methodologies with regard to separating survival curves of patient sub-groups despite using single omics profiles of patients compared to multiple omics profiles of SNF and NEMO. Pathway over-representation analysis is performed on the final clustering results to investigate the biological underpinnings characterizing each subtype., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Fueled by rapidly evolving comprehension of multifaceted nature of cancers, recently emerging preclinical and clinical data have supported researchers in the resolution of knowledge gaps to deepen the understanding of the molecular mechanisms. The extra-ordinary and bewildering chemical diversity encompassed by biologically active natural products continues to be of relevance to drug discovery. Accumulating evidence has spurred a remarkable evolution of concepts related to pharmacological target of oncogenic signaling pathways by polysaccharides in different cancers., Purpose: The objective of the current review is to provide new insights into study progress on anticancer effects of bioactive herbal polysaccharides., Methods: PubMed, Scopus, Web of Science, Embase, and other databases were searched for articles related to anticancer effects of polysaccharides. Searches were conducted to locate relevant publications published up to October 2022., Results: Polysaccharides have been reported to pleiotropically modulate TGF/SMAD, BMP/SMAD, TLR4, mTOR, CXCR4 and VEGF/VEGFR cascades. We have also summarized how different polysaccharides regulated apoptosis and non-coding RNAs. Additionally, this mini-review describes increasingly sophisticated understanding related to polysaccharides mediated tumor suppressive and anti-metastatic effects in tumor-bearing mice. We have also provided an overview of the clinical trials related to chemopreventive role of polysaccharides., Conclusion: Genomic and proteomic findings from these studies will facilitate 'next-generation' clinical initiatives in the prevention/inhibition of cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Cancer as a disease possess quite complicated pathophysiological implications and is among the prominent causes of morbidity and mortality on global scales. Anti-cancer chemotherapy, surgery, and radiation therapy are some of the present-day conventional treatment options. However, these therapeutic paradigms own several retreats, including lack of specificity, non-targeted toxicological implications, inefficient drug delivery to targeted cells, and emergence of cancer resistance, ultimately causing ineffective cancer management. Owing to the advanced and better biophysical characteristic features and potentiality for the tailoring and customizations and in several fashions, nanotechnology can entirely transubstantiate the cancer identification and its managements. Additionally, nanotechnology also renders several answers to present-day mainstream limitations springing-up in anti-cancer therapeutics. Nanocarriers, owing to their outstanding physicochemical features including but not limited to their particle size, surface morphological features viz. shape etc., have been employed in nanomedicinal platforms for targeting various transcription factors leading to worthy pharmacological outcomes. This transcription targeting activates the wide array of cellular and molecular events like antioxidant enzyme-induction, apoptotic cell death, cell-cycle arrest etc. These outcomes are obtained after the activation or inactivation of several transcription factors and cellular pathways. Further, nanoformulations have been precisely calibrated and functionalized with peculiar targeting groups for improving their efficiency to deliver the drug-payload to specified and targeted cancerous cells and tissues. This review undertakes an extensive, across-the-board and all-inclusive approach consisting of various studies encompassing different types of tailored and customized nanoformulations and nanomaterials designed for targeting the transcription factors implicated in the process of carcinogenesis, tumor-maturation, growth and metastasis. Various transcription factors viz. nuclear factor kappa (NF-κB), signal transducer and activators of transcription (STAT), Cmyc and Twist-related protein 1 (TWIST1) along with several types of nanoparticles targeting these transcription factors have been summarized here. A section has also been dedicated to the different types of nanoparticles targeting the hypoxia inducing factors. Efforts have been made to summarize several other transcription factors implicated in various stages of cancer development, growth, progression and invasion, and their targeting with different kinds of nanomedicinal agents., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Pyrrolidine molecules are a significant class of synthetic and natural plant metabolites, which show the diversity of pharmacological activities. An extensive variety of synthetic pyrrolidine compounds with numerous derivatization like spirooxindole, thiazole, metal complexes, coumarin, etc have revealed significant anticancer activity. Pyrrolidine molecules are found not only as potential anticancer candidates but also retain the lowest side effects. Depending upon the diverse substitution patterns of the derivatives, these molecules have demonstrated an incredible ability to regulate the various targets to give excellent anti-proliferative activities. Taking these into consideration, efforts have been taken by the scientific fraternity to design and develop a potent anticancer scaffold with negligible side effects. In the present review, we cover the latest advancements in the synthesis of pyrrolidine molecules which have promising anticancer activity toward numerous cancer cell lines. Additionally, it also highlights the effectiveness of derivatives via elucidation of Structural-Activity-Relationship (SAR) which is discussed in detail., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Masson SAS.)

Cancer is a multifactorial disease, and a wealth of information has enabled basic and clinical researchers to develop a better conceptual knowledge of the highly heterogeneous nature of cancer. Deregulations of spatio-temporally controlled transduction pathways play a central role in cancer progression. NRF2-driven signaling has engrossed significant attention because of its fundamentally unique features to dualistically regulate cancer progression. Context-dependent diametrically opposed roles of NRF2-induced signaling are exciting. More importantly, non-coding RNA (ncRNA) mediated regulation of NRF2 and interplay between NRF2 and ncRNAs have added new layers of complexity to already intricate nature of NRF2 signaling. There is a gradual enrichment in the existing pool of knowledge related to interplay between microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in different cancers. However, surprisingly, there are no clues about interplay between circular RNAs and NRF2 in various cancers. Therefore, future studies must converge on the functional characterization of additional important lncRNAs and circular RNAs, which regulated NRF2-driven signaling or, conversely, NRF2 transcriptionally controlled their expression to regulate various stages of cancer. SIGNIFICANCE STATEMENT: Recently, many researchers have focused on the NRF2-driven signaling in cancer progression. Excitingly, discovery of non-coding RNAs has added new layers of intricacy to the already complicated nature of KEAP1/NRF2 signaling in different cancers. These interactions are shaping the NRF2-driven signaling landscape, and better knowledge of these pathways will be advantageous in pharmacological modulation of non-coding RNA-mediated NRF2 signaling in various cancers., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

The tumor microenvironment (TME) is a complex network of cellular and non-cellular components surrounding the tumor. The cellular component includes fibroblasts, adipocytes, endothelial cells, and immune cells, while non-cellular components are tumor vasculature, extracellular matrix and signaling molecules. The tumor cells have constant close interaction with their surrounding TME components that facilitate their growth, survival, and metastasis. Targeting a complex TME network and its interaction with the tumor can offer a novel strategy to disrupt cancer cell progression. Curcumin, from turmeric rhizome, is recognized as a safe and effective natural therapeutic agent against multiple diseases including cancer. Here the effects of curcumin and its metabolites on tumor-TME interaction modulating ability have been described. Curcumin and its metabolites regulate TME by inhibiting the growth of its cellular components such as cancer-associated adipocytes, cancer-associated fibroblast, tumor endothelial cells, tumor-stimulating immune cells, and inducing anticancer immune cells. They also inhibit the interplay of tumor cells to TME by suppressing non-cellular components such as extracellular matrix, and associated tumor promoting signaling-pathways. In addition, curcumin inhibits the inflammatory environment, suppresses angiogenic factors, and increases antioxidant status in TME. Overall, curcumin has the capability to regulate TME components and their interaction with tumor cells.

Nutrigenomics utilizes high-throughput genomic technologies to reveal changes in gene and protein levels. Excitingly, ever-growing body of scientific findings has provided sufficient evidence about the interplay between diet and genes. Cutting-edge research and advancements in genomics, epigenetics and metabolomics have deepened our understanding on the role of dietary factors in the inhibition of carcinogenesis and metastasis. Dietary saponins, a type of triterpene glycosides, are generally found in Platycodon grandifloras , Dioscorea oppositifolia , asparagus, legumes, and sea cucumber. Wealth of information has started to shed light on pleiotropic mechanistic roles of dietary saponins in cancer prevention and inhibition. In this review, we have attempted to summarize the in vitro research of dietary saponins in the last two decades by searching common databases such as Google Scholar, PubMed, Scopus, and Web of Science. The results showed that dietary saponins exerted anti-cancer activities via regulation of apoptosis, autophagy, arrest cell cycle, anti-proliferation, anti-metastasis, and anti-angiogenesis, by regulation of several critical signaling pathways, including MAPK, PI3K/Akt/mTOR, NF-κB, and VEGF/VEGFR. However, there is no data about the dosage of dietary saponins for practical anti-cancer effects in human bodies. Extensive clinical studies are needed to confirm the effectiveness of dietary saponins for further commercial and medical applications.

The pursual of novel anticancer molecules from natural sources has gained worthwhile appreciation, and a significant fraction of conceptual knowledge has revolutionized our understanding about heterogeneous nature of cancer. Betulinic acid has fascinated interdisciplinary researchers due to its tremendous pharmacological properties. Ground-breaking discoveries have unraveled previously unprecedented empirical proof-of-concept about momentous chemopreventive role of betulinic acid against carcinogenesis and metastasis. Deregulation of cell signaling pathways has been reported to play a linchpin role in cancer progression and colonization of metastatically competent cancer cells to the distant organs for the development of secondary tumors. Importantly, betulinic acid has demonstrated unique properties to mechanistically modulate oncogenic transduction cascades. In this mini-review, we have attempted to provide a sophisticated compendium of regulatory role of betulinic acid in cancer chemoprevention. We have partitioned this multi-component review into different sections in which we summarized landmark research-works which highlighted betulinic acid mediated regulation of JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and ubiquitination pathways in the inhibition of cancer. In parallel, betulinic acid mediated regulation of signaling cascades and non-coding RNAs will be critically analyzed in cell culture and animal model studies. Better comprehension of the pharmaceutical features of betulinic acid and mapping of the existing knowledge gaps will be valuable in the translatability of preclinical studies into rationally designed clinical trials.

Seeman's pioneer idea has led to the foundation of DNA nanostructures, resulting in a remarkable advancement in DNA nanotechnology. Over the last few decades, remarkable advances in drug delivery techniques have resulted in the self-assembly of DNA for encapsulating candidate drug molecules. The nuclear targeting capability of DNA nanostructures is lies within their high spatial addressability and tremendous potential for active targeting. However, effective programming and assembling those DNA molecules remains a challenge, making the path to DNA nanostructures for real-world applications difficult. Because of their small size, most nanostructures are self-capable of infiltrating into the tumor cellular environment. Furthermore, to enable controlled and site-specific delivery of encapsulated drug molecules, DNA nanostructures are functionalized with special moieties that allow them to bind specific targets and release cargo only at targeted sites rather than non-specific sites, resulting in the prevention/limitation of cellular toxicity. In light of this, the current review seeks to shed light on the versatility of the DNA molecule as a targeting and encapsulating moiety for active drugs in order to achieve controlled and specific drug release with spatial and temporal precision. Furthermore, this review focused on the challenges associated with the construction of DNA nanostructures as well as the most recent advances in the functionalization of DNA nanostructures using various materials for controlled and targeted delivery of medications for cancer therapy., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

AKT serine-threonine kinase (AKT) and its effectors are essential for maintaining cell proliferation, apoptosis, autophagy, endoplasmic reticulum (ER) stress, mitochondrial morphogenesis (fission/fusion), ferroptosis, necroptosis, DNA damage response (damage and repair), senescence, and migration of cancer cells. Several lncRNAs and circRNAs also regulate the expression of these functions by numerous pathways. However, the impact on cell functions by lncRNAs and circRNAs regulating AKT and its effectors is poorly understood. This review provides comprehensive information about the relationship of lncRNAs and circRNAs with AKT on the cell functions of cancer cells. the roles of several lncRNAs and circRNAs acting on AKT effectors, such as FOXO, mTORC1/2, S6K1/2, 4EBP1, SREBP, and HIF are explored. To further validate the relationship between AKT, AKT effectors, lncRNAs, and circRNAs, more predicted AKT- and AKT effector-targeting lncRNAs and circRNAs were retrieved from the LncTarD and circBase databases. Consistently, using an in-depth literature survey, these AKT- and AKT effector-targeting database lncRNAs and circRNAs were related to cell functions. Therefore, some lncRNAs and circRNAs can regulate several cell functions through modulating AKT and AKT effectors. This review provides insights into a comprehensive network of AKT and AKT effectors connecting to lncRNAs and circRNAs in the regulation of cancer cell functions.

Cancer stem cells (CSCs) are self-renewing multipotent cells that play a vital role in the development of cancer drug resistance conditions. Various therapies like conventional, targeted, and radiotherapies have been broadly used in targeting and killing these CSCs. Among these, targeted therapy selectively targets CSCs and leads to overcoming disease recurrence conditions in cancer patients. Immunotoxins (ITs) are protein-based therapeutics with selective targeting capabilities. These chimeric molecules are composed of two functional moieties, i.e., a targeting moiety for cell surface binding and a toxin moiety that induces the programmed cell death upon internalization. Several ITs have been constructed recently, and their preclinical and clinical efficacies have been evaluated. In this review, we comprehensively discussed the recent preclinical and clinical advances as well as significant challenges in ITs targeting CSCs, which might reduce the burden of drug resistance conditions in cancer patients from bench to bedside., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Nursing education suffers from a lack of high-quality clinical experiences for students, especially among medical specialty groups such as cancer patients, in Saudi Arabia. A paucity of empirical evidence is supporting simulation in education and the transfer of psychomotor skills to patient care. In particular, although generally recognized as an essential oncology nursing skill, effective strategies for teaching the management of chemotherapy extravasation to students have not been investigated., Purpose: To investigate the effects of high-fidelity simulation (HFS) technology on the competency of nursing students in the management of chemotherapy extravasation and the transfer of this skill from traditional learning labs to clinical settings., Methods: A quasi-experimental study comprising a two-group pretest-posttest with repeated measures was used. The intervention was a scenario-based, HFS. Third-year students (n = 68) from a nursing program were randomly allocated to either intervention or control groups. Competency was measured in both groups using the same standardized assessment checklist., Results: Competency scores were lower in the control group compared to the intervention group at both posttesting times. These results, however, were not statistically significant. There was no statistically significant difference between the groups regarding skill transfer., Conclusions: Nursing faculty can use either HFS or traditional learning methods to effectively teach students how to manage chemotherapy extravasation and transfer this skill to clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. The authors alone are responsible for the content and writing of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Noncoding RNAs (ncRNAs) regulation of various diseases including cancer has been extensively studied. Reactive oxidative species (ROS) elevated by oxidative stress are associated with cancer progression and drug resistance, while autophagy serves as an ROS scavenger in cancer cells. However, the regulatory effects of ncRNAs on autophagy and ROS in various cancer cells remains complex. Here, we explore how currently investigated ncRNAs, mainly miRNAs and lncRNAs, are involved in ROS production through modulating antioxidant genes. The regulatory effects of miRNAs and lncRNAs on autophagy-related (ATG) proteins to control autophagy activity in cancer cells are discussed. Moreover, differential expression of ncRNAs in tumor and normal tissues of cancer patients are further analyzed using The Cancer Genome Atlas (TCGA) database. This review hypothesizes links between ATG genes- or antioxidant genes-modulated ncRNAs and ROS production, which might result in tumorigenesis, malignancy, and cancer recurrence. A better understanding of the regulation of ROS and autophagy by ncRNAs might advance the use of ncRNAs as diagnostic and prognostic markers as well as therapeutic targets in cancer therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Data obtained from cutting-edge research have shown that deregulated epigenetic marks are critical hallmarks of cancer. Rapidly emerging scientific evidence has helped in developing a proper understanding of the mechanisms leading to control of cellular functions, from changes in chromatin accessibility, transcription and translation, and in post-translational modifications. Firstly, mechanisms of DNA methylation and demethylation are introduced, as well as modifications of DNA and RNA, with particular focus on N6-methyladenosine (m6A), discussing the effects of these modifications in normal cells and in malignancies. Then, chromatin modifying proteins and remodelling complexes are discussed. Many enzymes and accessory proteins in these complexes have been found mutated or have undergone differential splicing, leading to defective protein complexes. Epigenetic mechanisms acting on nucleosomes by polycomb repressive complexes and on chromatin by SWI/SNF complexes on nucleosome assembly/disassembly, as well as main mutated genes linked to cancers, are reviewed. Among enzymes acting on histones and other proteins erasing the reversible modifications are histone deacetylases (HDACs). Sirtuins are of interest since most of these enzymes not only deacylate histones and other proteins, but also post-translationally modify proteins adding a Mono-ADP-ribose (MAR) moiety. MAR can be read by MACRO-domain containing proteins such as histone MacroH2A1, with specific function in chromatin assembly. Finally, recent advances are presented on non-coding RNAs with a scaffold function, prospecting their role in assembly of chromatin modifying complexes, recruiting enzyme players to chromatin regions. Lastly, the imbalance in metabolites production due to mitochondrial dysfunction is presented, with the potential of these metabolites to inhibit enzymes, either writers, readers or erasers of epitranscriptome marks. In the perspectives, studies are overwied on drugs under development aiming to limit excessive enzyme activities and to reactivate chromatin modifying complexes, for therapeutic application. This knowledge may lead to novel drugs and personalised medicine for cancer patients., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Landmark discoveries in molecular oncology have provided a wide-angle overview of the heterogenous and therapeutically challenging nature of cancer. The power of modern 'omics' technologies has enabled researchers to deeply and comprehensively characterize molecular mechanisms underlying cellular functions. Interestingly, high-throughput technologies have opened new horizons for the design and scientific fool-proof evaluation of the pharmacological properties of targeted chemical compounds to tactfully control the activities of the oncogenic protein networks. Groundbreaking discoveries have galvanized the expansion of the repertoire of available pharmacopoeia to therapeutically target a myriad of deregulated oncogenic pathways. Natural product research has undergone substantial broadening, and many of the drugs which constitute the backbone of modern pharmaceuticals have been derived from the natural cornucopia. Baicalein has gradually gained attention because of its unique ability to target different oncogenic signal transduction cascades in various cancers. We have partitioned this review into different sub-sections to provide a broader snapshot of the oncogenic pathways regulated by baicalein. In this review, we summarize baicalein-mediated targeting of WNT/β-catenin, AKT/mTOR, JAK/STAT, MAPK, and NOTCH pathways. We also critically analyze how baicalein regulates non-coding RNAs (microRNAs and long non-coding RNAs) in different cancers. Finally, we conceptually interpret baicalein-mediated inhibition of primary and secondary growths in xenografted mice.

Cancer is a life-threatening and multifaceted disease. Pioneering research works in the past three decades have mechanistically disentangled intertwined signaling networks which play contributory roles in carcinogenesis and metastasis. Phenomenal strides have been made in leveraging our scientific knowledge altogether to a new level of maturity. Rapidly accumulating wealth of information has underlined a myriad of transduction cascades which can be pharmaceutically exploited for cancer prevention/inhibition. Natural products serve as a treasure trove and compel interdisciplinary researchers to study the cancer chemopreventive roles of wide-ranging natural products in cell culture and preclinical studies. Experimental research related to thymoquinone has gradually gained momentum because of the extra-ordinary cancer chemopreventive multifunctionalities of thymoquinone. In this mini-review, we provide an overview of different cell signaling cascades reported to be regulated by thymoquinone for cancer chemoprevention. Essentially, thymoquinone efficacy has also been notably studied in animal models, which advocates for a rationale-based transition of thymoquinone from the pre-clinical pipeline to clinical trials.

Background: Transforming growth factor beta (TGF-β) superfamily has key role in cell proliferation which leads to tumor promoting activities at metastatic stage of cancer. Inhibition of transforming growth factor beta receptor (TGFβR) signaling pathway can provide better therapeutic strategy to control cancer. Natural products are best known for their safety, less toxic nature, antioxidant characteristics making them a promising candidate to inhibit TGFβR signaling pathway., Methods and Results: Crude methanolic extracts (CMEs) of 16 selected plants were prepared by using maceration method and subjected to phytochemical assays for identification of major phytometabolites particularly cancer chemopreventive antioxidant constituents. Total flavonoid content of all plants CME was > 0.6 mg/ml exhibiting the Cichorium intybus contains comparatively highest amount of total flavonoid content (0.53 mg/ml). Scanvenging activity of all plants was determined having IC 50 ranges between 2 and 88 (µg/ml) while Moringa oleifera revealed the maximum scavenging activity (IC 50 2.03 µg/ml). Comparative cytotoxicity of plant extracts was evaluated in HUH and MCF-7 cell lines using 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) colorimetric assay. The nine active plant extracts i.e. Fagonia cretica, Argemone Mexicana, Rubus fruticosus, M. oleifera, Punica granatum, Cichorium intybus, Xanthium strumarium, Carissa opaca, Cyperus rotundus were identified based on their high antiproliferative activity > 50% against cancer cell lines and subjected to relative expression studies. Modulation of TGFβ signaling molecules (i.e.TGFβR1, 2 & 3, SMAD3, SMAD5) and ubiquitous proteins i.e. SMURF1 and SMURF2 genetic expression by potent extracts was determined by RT-PCR using GAPDH (housekeeping gene) as gene of reference., Conclusions: This present study revealed that CME of Fagonia cretica and Argemone mexicana significantly inhibit TGF beta mediated signaling cascade by downregulating the gene expression fold change > 1 of TGFβR 1, 2 & 3 and receptor associated complex protein SMAD3 as compared to control., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Groundbreaking discoveries in molecular oncology have leveraged our understanding altogether to a new level. Mapping of plethora of cell signaling pathways has enabled researchers to drill down deep into the intermeshed regulatory networks which crosstalk to promote carcinogenesis and metastasis. More importantly, discovery of non-coding RNAs has added new layers of complexity to already complicated nature of cell signaling pathways. The discovery of circular RNAs (circRNAs) has opened the door to an ever-widening understanding of cellular processes that are controlled or influenced by circRNAs. In this review, we have summarized most recent advancements in our understanding related to interplay between circular RNAs and microRNAs for the regulation of NOTCH, Wnt/β-catenin, Hippo, SHH/GLI, JAK/STAT and TGF/SMAD pathways in different cancers., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Advancements in single-cell RNA sequencing technologies have enabled us to deconvolve immune system heterogeneity by identification of functionally distinct immune cell subsets in disease and health. Discovery of non-coding RNAs has opened new horizons for re-interpretation of regulatory roles of myriad of cell signaling pathways in immunology and oncology. Role of miRNAs, circular RNAs and long non-coding RNAs (lncRNAs) in the context of immunomodulation has just begun to be uncovered and future studies may further expand the repertoire of non-coding RNAs implicated in the regulatory circuits. One of the most recent and exciting aspect in molecular immunology is the delivery of non-coding RNAs through exosomes to the recipient cells which results in the re-wiring of different pathways and protein networks in recipient cells. Broader understanding of all of the layers of regulation in this system can provide useful information that could be harnessed to rationally translate laboratory findings into clinically effective therapeutics., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Natural product research is a cornerstone of the architectural framework of clinical medicine. Berbamine is a natural, potent, pharmacologically active biomolecule isolated from Berberis amurensis . Berbamine has been shown to modulate different oncogenic cell-signaling pathways in different cancers. In this review, we comprehensively analyze how berbamine modulates deregulated pathways (JAK/STAT, CAMKII/c-Myc) in various cancers. We systematically analyze how berbamine induces activation of the TGF/SMAD pathway for the effective inhibition of cancer progression. We also summarize different nanotechnological strategies currently being used for proficient delivery of berbamine to the target sites. Berbamine has also been reported to demonstrate potent anti-cancer and anti-metastatic effects in tumor-bearing mice. The regulation of non-coding RNAs by berbamine is insufficiently studied, and future studies must converge on the identification of target non-coding RNAs. A better understanding of the regulatory role of berbamine in the modulation of non-coding RNAs and cell-signaling pathways will be advantageous in the effective translation of laboratory findings to clinically effective therapeutics.

Around the world, cancer care services are facing many operational challenges. Operations management research can provide important solutions to these challenges, from screening and diagnosis to treatment. In recent years, the growth in the number of papers published on cancer care operations management (CCOM) indicates that development has been fast. Within this context, the objective of this research was to understand the evolution of CCOM through a comprehensive study and an up-to-date bibliometric analysis of the literature. To achieve this aim, the Web of Science Core Collection database was used as the source of bibliographic records. The data-mining and quantitative tools in the software Biblioshiny were used to analyze CCOM articles published from 2010 to 2021. First, a historical analysis described CCOM research, the sources, and the subfields. Second, an analysis of keywords highlighted the significant developments in this field. Third, an analysis of research themes identified three main directions for future research in CCOM, which has 11 evolutionary paths. Finally, this paper discussed the gaps in CCOM research and the areas that require further investigation and development., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.

Purpose: The COVID-19 pandemic has exacerbated cancer treatment disparities, including accessibility to resources. We describe the process and outcomes of a new proactive, virtual nurse-led, resource center navigation model enhanced by using volunteer patient navigators. Using known patient risk factors, this model provides interventions to reduce barriers to care, with an emphasis on non-English-speaking populations., Methods: Patients were included if they (1) were in active cancer treatment and (2) had one or more known risk factors: distance from cancer hospital, needing complex care, 65 years or older, malignant hematological diagnosis, new treatment start, lives alone, non-English speaker, or a new hospital discharge. Nurse navigators triaged referrals to appropriate team members who identified and addressed barriers to care., Results: The program engaged with 586 adult cancer patients over 1459 encounters. The most common risk factors included distance (59.7%), complex care (48.8%), and new treatment start (43.5%). The most common interventions were core education (69.4%), emotional support (61.2%), and education (35.7%). Statistical differences were found between Spanish-speaking (n = 118) and non-Spanish-speaking patients (n = 468). While Spanish-speaking patients had fewer risk factors (1.95 vs. 2.80, p ≤ .0001), they had nearly double the number of visits (4.27 vs. 2.04, p ≤ .0001) and 69% more interventions (8.26 vs. 4.90, p ≤ .0001). Many patients (42.7%) required follow-up visits., Conclusion: We successfully established a new navigation model for the resource center during the pandemic that identified and reduced barriers to care, particularly in the Spanish-speaking population., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

It is becoming progressively more understandable that pharmaceutical targeting of drug-resistant cancers is challenging because of intra- and inter-tumor heterogeneity. Interestingly, naturally derived bioactive compounds have unique ability to modulate wide-ranging deregulated oncogenic cell signaling pathways. In this review, we have focused on the available evidence related to regulation of PI3K/AKT/mTOR, Wnt/β-catenin, NF-κB and TRAIL/TRAIL-R by fisetin in different cancers. Fisetin has also been shown to inhibit the metastatic spread of cancer cells in tumor-bearing mice. We have also summarized how fisetin regulated autophagy in different cancers. In addition, this review also covers fisetin-mediated regulation of VEGF/VEGFR, EGFR, necroptosis and Hippo pathway. Fisetin has entered into clinical trials particularly in context of COVID19-associated inflammations. Furthermore, fisetin mediated effects are also being tested in clinical trials with reference to osteoarthritis and senescence. These developments will surely pave the way for full-fledge and well-designed clinical trials of fisetin in different cancers. However, we still have to comprehensively analyze and fully unlock pharmacological potential of fisetin against different oncogenic signaling cascades and non-coding RNAs. Fisetin has remarkable potential as chemopreventive agent and future studies must converge on the identification of additional regulatory roles of fisetin for inhibition and prevention of cancers., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

There has been an exponential growth in the field of molecular oncology and cutting-edge research has enabled us to develop a better understanding of therapeutically challenging nature of cancer. Based on the mechanistic insights garnered from decades of research, puzzling mysteries of multifaceted nature of cancer have been solved to a greater extent. Our rapidly evolving knowledge about deregulated oncogenic cell signaling pathways has allowed us to dissect different oncogenic transduction cascades which play critical role in cancer onset, progression and metastasis. Pharmacological targeting of deregulated pathways has attracted greater than ever attention in the recent years. Henceforth, discovery and identification of high-quality biologically active chemicals and products is gaining considerable momentum. There has been an explosion in the dimension of natural product research because of tremendous potential of chemopreventive and pharmaceutical significance of natural products. Schisandrin is mainly obtained from Schisandra chinensis. Schisandrin has been shown to be effective against different cancers because of its ability to inhibit/prevent cancer via modulation of different cell signaling pathways. Importantly, regulation of non-coding RNAs by schisandrin is an exciting area of research that still needs detailed and comprehensive research.   However, we still have unresolved questions about pharmacological properties of schisandrin mainly in context of its regulatory role in TGF/SMAD, SHH/GLI, NOTCH and Hippo pathways.

Natural products have historically been invaluable as a premium source of therapeutic agents. Recent advancements in genomics and structural biology have portrayed a high-resolution landscape of the diversity of proteins targeted by pharmacologically active products from natural sources. Natural product research has generated valuable wealth of information and cutting-edge research-works have leveraged our conceptual knowledge altogether to a new level. Wogonin (5,7-dihydroxy-8-methoxyflavone) is an O-methylated flavone and has attracted noteworthy appreciation because of its ability to pharmacologically target plethora of cell signaling pathways in different cancers. In this mini-review, we have gathered scattered pieces of available scientific evidence to summarize how wogonin pharmaceutically targeted Wnt/?-catenin, JAK/STAT, VEGF/VEGFR and TRAIL-driven apoptotic pathways in wide variety of cancers. We have also critically analyzed how wogonin prevented carcinogenesis and metastasis in tumor-bearing mice. Although researchers have uncovered pleiotropic role of wogonin in the regulation of different oncogenic signaling cascades but there are visible knowledge gaps in our understanding related to regulation of non-coding RNAs by wogonin. Future studies must converge on the unraveling of additional drug targets for wogonin to achieve a fuller and realistic understanding of the chemopreventive properties of wogonin.

The growing complexity of metastasis has sparked tremendous interest in unraveling of the underlying mechanisms which play fundamental role in cancer progression and metastasis. Ground-breaking discoveries in metastasis research have greatly enhanced our understanding about intricate nature of metastasis. Bioactive chemicals obtained from citrus fruits have gained noteworthy appreciation because of significant cancer chemopreventive roles. Deregulated oncogenic signaling cascades play central role in metastasis. Emerging evidence has started to shed light on the metastasis inhibitory properties of naringin, naringenin, tangeretin, nobiletin, hesperidin and hesperetin in different cancer cell lines and xenografted mice. Wnt/?-catenin, TGF/SMAD and NOTCH signaling cascades have been shown to play linchpin role in carcinogenesis and metastasis. There is emerging evidence related to pharmacological targeting of Wnt/?-catenin, TGF/SMAD and NOTCH by citrus-derived bioactive components. These findings are indeed encouraging and will enable researchers to gain further insights into pharmacological targeting of oncogenic pathways to inhibit and prevent metastasis.

Pomegranate has attracted overwhelming appreciation as a highly nutritional food for health improvement and treatment of various diseases. Based on the exciting insights gleaned from decades of research, it seems exciting to note that pomegranate and its bioactive components show high-quality pharmacological properties. Pomegranate has been shown to be effective against different cancers in xenografted mice. However, realistically, we still have incomplete understanding of the true potential of pomegranate as versatile regulator of deregulated oncogenic transduction cascades in different cancers. In this review I will exclusively focus on modulation of oncogenic signaling cascades by pomegranate or its bioactive components in different cancers. Gaze through the lens indicates that certain hints have emerged which highlight regulatory role of pomegranate in Wnt/β-catenin, mTOR and NF-κB-driven pathways. However, there are unresolved questions related to targeting of TGF/SMAD, JAK/STAT, SHH/GLI, NOTCH by pomegranate in variety of cancers. In accordance with same approach, pomegranate mediated regulations of TRAIL/TRAIL-R and FasL/Fas have also been insufficiently studied. Therefore, I will attempt to analyze and discuss the existing knowledge gaps in our understanding related to ability of pomegranate to modulate myriad of protein networks. It will not be wrong if we say that researchers have just started to scratch the surface of a new and mysterious web of medicinal properties of pomegranate to target multiple transduction cascades., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Research over decades has enabled us in developing a better understanding of the multifaceted and heterogeneous nature of cancer. High-throughput technologies have helped the researchers in unraveling of the underlying mechanisms which centrally regulate cancer onset, metastasis and drug resistance. Our rapidly expanding knowledge about signal transduction cascade has added another layer of complexity to already complicated nature of cancer. Deregulation of cell signaling pathways played a linchpin role in carcinogenesis and metastasis. Cucurbitacins have gained tremendous attention because of their remarkable pharmacological properties and considerable ability to mechanistically modulate myriad of cell signaling pathways in different cancers. In this review, we have attempted to provide a mechanistic and comprehensive analysis of regulation of oncogenic pathways by cucurbitacins in different cancers. We have partitioned this review into separate sections for exclusive analysis of each signaling pathway and critical assessment of the knowledge gaps. In this review, we will summarize most recent and landmark developments related to regulation of Wnt/β-catenin, JAK/STAT, mTOR, VEGFR, EGFR and Hippo pathway by cucurbitacins. Moreover, we will also address how cucurbitacins regulate DNA damage repair pathway and TRAIL-driven signaling in various cancers. However, there are still outstanding questions related to regulation of SHH/GLI, TGF/SMAD and Notch-driven pathway by cucurbitacins in different cancers. Future studies must converge on the analysis of full-fledge potential of cucurbitacins by in-depth analysis of these pathways and how these pathways can be therapeutically targeted by cucurbitacins., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Mitochondrial dysfunction and oxidative stress are prominent features of a plethora of human disorders. Dysregulation of mitochondrial functions represents a common pathogenic mechanism of diseases such as neurodegenerative disorders and cancer. The maintenance of the Nicotinamide adenine dinucleotide (NAD+) pool, and a positive NAD+/NADH ratio, are essential for mitochondrial and cell functions. The synthesis and degradation of NAD+ and transport of its key intermediates among cell compartments play an important role in maintaining optimal NAD levels, for the regulation of NAD+-utilizing enzymes, such as sirtuins (Sirt), poly-ADP-ribose polymerases, and CD38/157 enzymes, either intracellularly as well as extracellularly. In this review, we present and discuss the links between NAD+, NAD+-consuming enzymes, mitochondria functions, and diseases. Attempts to treat various diseases with supplementation of NAD+ cycling intermediates and inhibitors of sirtuins and ADP-ribosyl transferases may highlight a possible therapeutic approach for therapy of cancer and neurodegenerative diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Irrespective of sex and age, cancer is the leading cause of mortality around the globe. Therapeutic incompliance, unwanted effects, and economic burdens imparted by cancer treatments, are primary health challenges. The heritable features in gene expression that are propagated through cell division and contribute to cellular identity without a change in DNA sequence are considered epigenetic characteristics and agents that could interfere with these features and are regarded as potential therapeutic targets. The genetic modification accounts for the recurrence and uncontrolled changes in the physiology of cancer cells. This review focuses on plant-derived flavonoids as a therapeutic tool for cancer, attributed to their ability for epigenetic regulation of cancer pathogenesis. The epigenetic mechanisms of various classes of flavonoids including flavonols, flavones, isoflavones, flavanones, flavan-3-ols, and anthocyanidins, such as cyanidin, delphinidin, and pelargonidin, are discussed. The outstanding results of preclinical studies encourage researchers to design several clinical trials on various flavonoids to ascertain their clinical strength in the treatment of different cancers. The results of such studies will define the clinical fate of these agents in future.

NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasomes are multitasking intracellular sensors having characteristically unique ability to detect myriad of microbial motifs and endogenous danger signals which promote structural assembly of NLRP3 inflammasome thus enabling it to perform instrumental roles. Detailed mechanistic insights revealed that molecularly assembled NLRP3 inflammasomes stimulated caspase-1-driven release of the pro-inflammatory cytokines. NLRP3 has been shown to play fundamental role in the regulation of cancer progression and metastasis. Recently emerging cutting-edge research-works have started to shed light on the involvement of non-coding RNAs in the regulation of NLRP3 in different cancers. MicroRNAs, lncRNAs and circular RNAs have been shown to modulate NLRP3 in different diseases. However, we still have incomplete information about regulation of NLRP3 by circular RNAs in various cancers. In this review, we will comprehensively analyze how different microRNAs and long non-coding RNAs modulate NLRP3 in human cancers. Emerging evidence has started to scratch the surface of the participation of miRNAs and lncRNAs in the regulation of NLRP3. Xenografted mice-based studies have also enabled us to develop a better comprehension of interplay between miRNAs, lncRNAs and NLRP3. Hopefully, detailed analysis of contextual regulation of NLRP3 by oncogenic and tumor suppressor miRNAs, lncRNAs and circRNAs will be helpful in getting a step closer to the personalized medicine.

Cancer is a therapeutically challenging disease because of its heterogeneous and multifaceted nature. Decades of research have sequentially and systematically enabled us to develop a sharper and better understanding of the heterogeneous nature of cancer. Genetic, genomic and proteomic studies have unraveled wide-ranging signaling cascades which play cornerstone role in disease onset and progression. More importantly, activation of pro-survival signaling and loss of apoptosis also play critical role in cancer progression. TRAIL-mediated signaling pathway has emerged as one of the most comprehensively analyzed cascade because of its exceptional ability to target cancer cells while leaving normal cells intact. TRAIL discovery and landmark achievements related to TRAIL/TRAIL-receptor signaling pathway attracted the attention of researchers. Therefore, scientists started to add missing pieces to an incomplete jig-saw puzzle and allowed contemporary researchers to conceptualize a better molecular snapshot of TRAIL-induced signaling in various cancers. Circumstantial evidence illuminated a functionally unique "push and pull" between anti-apoptotic and pro-apoptotic proteins in different cancers. Overexpression of anti-apoptotic proteins and inactivation of pro-apoptotic proteins shifted the balance towards loss of apoptosis. There has been a breakneck increase in the number of clinical trials related to TRAIL-based therapeutics which validate the true pharmacological potential of TRAIL-based therapeutics as effective anticancer agents. However, apart from advancements in our clinical understanding about the efficacy of TRAIL-based therapeutics, researchers have also faced setbacks in the field of translational medicine. Therefore, in this review, we have attempted to set spotlight on the most recent and landmark discoveries which have leveraged our understanding related to TRAIL-mediated signaling altogether to a new level.

There has always been a keen interest of basic and clinical researchers to search for cancer therapeutics having minimum off-target effects and maximum anticancer activities. In accordance with this approach, there has been an explosion in the field of natural products research in the past few decades because of extra-ordinary list of natural extracts and their biologically and pharmacologically active constituents having significant medicinal properties. Apparently, luteolin-mediated anticancer effects have been investigated in different cancers but there is superfluousness of superficial data. Generalized scientific evidence encompassing apoptosis, DNA damage and anti-inflammatory effects has been reported extensively. However, how luteolin modulates deregulated oncogenic pathways in different cancers has not been comprehensively uncovered. In this review we have attempted to focus on cutting-edge research which has unveiled remarkable abilities of luteolin to modulate deregulated oncogenic pathways in different cancers. We have partitioned the review into various sections to separately discuss advancements in therapeutic targeting of oncogenic protein networks. We have provided detailed mechanistic insights related to JAK-STAT signaling and summarized how luteolin inhibited STAT proteins to inhibit STAT-driven gene network. We have also individually analyzed Wnt/β-catenin and NOTCH pathway and how luteolin effectively targeted these pathways. Mapping of the signaling landscape has revealed that NOTCH pathway can be targeted therapeutically. NOTCH pathway was noted to be targeted by luteolin. We have also conceptually analyzed how luteolin restored TRAIL-induced apoptosis in resistant cancers. Luteolin induced an increase in pro-apoptotic proteins and efficiently inhibited anti-apoptotic proteins to induce apoptosis. Luteolin mediated regulation of non-coding RNAs is an exciting and emerging facet. Excitingly, there is sequential and systematic accumulation of clues which have started to shed light on intricate regulation of microRNAs by luteolin in different cancers. Collectively, sophisticated information will enable us to develop a refined understanding of the multi-layered regulation of signaling pathways and non-coding RNAs by luteolin in different cancers., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

With the recent technological advancements, a new golden era of natural products drug discovery has dawned. Increasingly it is being realized that structural modularity of many pharmacologically active products derived natural sources allows a building-block approach which can be exploited for analysis of regulation of deregulated oncogenic protein networks in different cancers. Piceatannol has been shown to effectively modulate JAK/STAT, Wnt/β-catenin, mTOR pathway in different cancers. In addition, certain hints have emerged which shed light on the regulation of microRNAs by piceatannol in some cancers. Regulation of deregulated oncogenic pathways by Piceatannol is gradually capturing attention and might be helpful in the multi-targeting of deregulated oncogenic networks in cancers.

Background: Pain is one of the most common and undesired symptoms in cancer patients, affecting patients' physical and psychological well-being. Barriers to effective pain management in cancer patients need to be identified and addressed by clinicians., Aims: The purpose of this study was to explore the barriers to effective cancer pain management from the perspective of cancer patients and their family members., Methods: A qualitative research design was employed. Semistructured interviews were conducted with 10 patients and 10 family caregivers to elucidate their perspectives regarding the barriers to effective cancer pain management in Jordan., Results: Regulatory factors, knowledge deficit, and the use of religious and cultural strategies to cope with pain were major barriers to effective cancer pain management. Although effective cancer pain management is highly recommended, the participants' cultural beliefs deeply appreciated pain tolerance and discouraged effective treatment of cancer pain., Conclusion: Tailoring culturally appropriate educational programs regarding effective cancer pain management could facilitate pain management among patients with cancer., (Copyright © 2019 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Epigenetic abnormalities and aberrant expression of non-coding RNAs are two emerging features of cancer cells, both of which are responsible for deregulated gene expression. In this review, we describe the interplay between the two. Specific themes include epigenetic silencing of tumor suppressor miRNAs, epigenetic activation of oncogenic miRNAs, epigenetic aberrations caused by miRNAs, and naturally occurring compounds which modulate miRNA expression through epigenetic mechanisms., (Copyright © 2019. Published by Elsevier Ltd.)

Large-scale sequencing methodologies have helped us identify numerous genomic alterations and we have started to scratch the surface of many new targets for treatment of cancer and the associated predictive biomarkers. TRAIL (TNF-related apoptosis-inducing ligand) is a highly appreciated anti-cancer molecule because of its ability to selectively target cancer cells. However, confluence of information suggests that cancer cells develop resistance against TRAIL-based therapeutics. It is being realized that overexpression of anti-apoptotic proteins and inactivation of pro-apoptotic proteins significantly impairs TRAIL triggered apoptosis, particularly in clinical settings. Re-balancing of pro-and anti-apoptotic proteins and upregulation of death receptors with functionally active extrinsic and intrinsic apoptotic pathways are necessary to sensitize cancer cells to TRAIL based therapeutics. microRNAs (miRNAs) are involved in regulation of myriad of molecular processes and characterized into oncogenic and tumor suppressor miRNAs. Accumulating data has identified miRNAs which positively or negatively regulate TRAIL mediated signaling in cancer cells, helping us understand different steps at which TRAIL-mediated apoptotic signaling can be targeted. Here, we assess the status of our understanding of the mechanisms related to miRNA regulation of TRAIL mediated signaling, as well as the existing gaps therein, and discuss the challenges and opportunities that will help us get closer to personalized medicine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)