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Cancer is a multifaceted disease influenced by both intrinsic cellular traits and extrinsic factors, with the tumor microenvironment (TME) being crucial for cancer progression. To satisfy their high proliferation and aggressiveness, cancer cells always plunder large amounts of nutrients and release various signals to their surroundings, forming a dynamic TME with special metabolic, immune, microbial and physical characteristics. Due to the neglect of interactions between tumor cells and the TME, traditional cancer therapies often struggle with challenges such as drug resistance, low efficacy, and recurrence. Importantly, the development of gene editing technologies, particularly the CRISPR-Cas system, offers promising new strategies for cancer treatment. Combined with nanomaterial strategies, CRISPR-Cas technology exhibits precision, affordability, and user-friendliness with reduced side effects, which holds great promise for profoundly altering the TME at the genetic level, potentially leading to lasting anticancer outcomes. This review will delve into how CRISPR-Cas can be leveraged to manipulate the TME, examining its potential as a transformative anticancer therapy., (© 2024 Wiley-VCH GmbH.)

Increasing evidence highlights the importance of immune mechanoregulation in establishing and sustaining tumor-specific cytotoxicity required for desirable immunotherapeutic outcomes. However, the molecular connections between mechanobiological inputs and outputs and the designated immune activities remain largely unclear. Here, we show that partial inhibition of non-muscle myosin II (NM II) augmented the traction force exerted by T cells and potentiated T cell cytotoxicity against tumors. By using T cells from mice and patients with cancer, we found that NM II is required for the activity of NKX3-2 in maintaining the expression of ADGRB3, which shapes the filamentous actin (F-actin) organization and ultimately attributes to the reduced traction force of T cells in the tumor microenvironment. In animal models, suppressing the NM II-NKX3-2-ADGRB3 pathway in T cells effectively suppressed tumor growth and improved the efficacy of the checkpoint-specific immunotherapy. Overall, this work provides insights into the biomechanical regulation of T cell cytotoxicity that can be exploited to optimize clinical immunotherapies.

Non-coding RNAs (ncRNAs) have become important modulators of gene expression and biological processes, contributing significantly to the initiation and spread of cancer. This study focuses on the complex interactions between ncRNAs and two major signaling pathways-Wnt/β-catenin signaling and cyclin-dependent kinase (CDK)-linked to cancer. We provide an overview of current research on the modulation of these pathways in many cancer types by distinct classes of ncRNAs, such as miRNAs, lncRNAs, and circRNAs. The review focuses on the processes by which ncRNAs regulate cancer cell survival, proliferation, and metastasis. These mechanical processes include CDK activity, the activation of the Wnt/β-catenin cascade and cell cycle advancement. We also discuss the importance of ncRNAs in drug resistance and treatment outcomes, as well as prognosis markers (diagnostic) and therapeutic targets for cancer. Understanding these complex regulatory networks may help in a large way to improve cancer research and diagnosis - but also perhaps treat patients more effectively., 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.)

Phenylboronic acid (PBA) is recognized as one of the most promising cancer cell binding modules attributed to its potential to form reversible and dynamic boronic ester covalent bonds. Exploring the advanced chemical versatility of PBA is crucial for developing new anticancer therapeutics. The presence of a specific Lewis acidic boron atom-based functional group and a Π-ring-connected ring has garnered increasing interest in the field of cancer immunotherapy. PBA-derivatized functional biomaterials can form reversible bonds with diols containing cell surface markers and proteins. This review primarily focuses on the following topics: (1) the importance and versatility of PBA, (2) different PBA derivatives with pKa values, (3) specific key features of PBA-mediated biomaterials, and (4) cell surface activity for cancer immunotherapy applications. Specific key features of PBA-mediated materials, including sensing, bioadhesion, and gelation, along with important synthesis strategies, are highlighted. The utilization of PBA-mediated biomaterials for cancer immunotherapy, especially the role of PBA-based nanoparticles and PBA-mediated cell-based therapeutics, is also discussed. Finally, a perspective on future research based on PBA-biomaterials for immunotherapy applications is presented., 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 B.V. All rights reserved.)

The cell cycle is the sequence of events orchestrated by a complex network of cell cycle proteins. Unlike normal cells, mature neurons subsist in a quiescent state of the cell cycle, and aberrant cell cycle activation triggers neuronal death accompanied by neurodegeneration. The periodicity of cell cycle events is choreographed by various mechanisms, including DNA damage repair, oxidative stress, neurotrophin activity, and ubiquitin-mediated degradation. Given the relevance of cell cycle processes in cancer and neurodegeneration, this review delineates the overlapping cell cycle events, signaling pathways, and mechanisms associated with cell cycle aberrations in cancer and the major neurodegenerative disorders. We suggest that dysregulation of some common fundamental signaling processes triggers anomalous cell cycle activation in cancer cells and neurons. We discussed the possible use of cell cycle inhibitors for neurodegenerative disorders and described the associated challenges. We propose that a greater understanding of the common mechanisms driving cell cycle aberrations in cancer and neurodegenerative disorders will open a new avenue for the development of repurposed drugs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The design and development of fluorescent materials for detecting cancer-related enzymes are crucial for cancer diagnosis and treatment. Herein, we present a substituted rhodamine derivative for the chromogenic and fluorogenic detection of the cancer-relevant enzyme γ -glutamyltranspeptidase (GGT). Initially, the probe is non-chromic and non-emissive due to its spirolactam form, which hinders extensive electronic delocalization over broader pathway. However, selective enzymatic cleavage of the side-coupled group triggers spirolactam ring opening, resulting in electronic flow across the rhodamine skeleton, and reduces the band gap for low-energy electronic transitions. This transformation turns the reaction mixture from colorless to intense pink, with prominent UV and fluorescence bands. The sensor's selectivity was tested against various human enzymes, including urease, alkaline phosphatase, acetylcholinesterase, tyrosinase, and cyclooxygenase, and showed no response. Absorption and fluorescence titration analyses of the probe upon incremental addition of GGT into the probe solution revealed a consistent increase in both absorption and emission spectra, along with intensified pink coloration. The cellular toxicity of the receptor was evaluated using the MTT assay, and bioimaging analysis was performed on BHK-21 cells, which produced bright red fluorescence, demonstrating the probe's excellent cell penetration and digestion capabilities for intracellular analytical detection. Molecular docking results supported the fact that probe-4 made stable interactions with the GGT active site residues.

Cancer remains the leading cause of human death worldwide. Compared to traditional therapies, tumor immunotherapy has received a lot of attention and research focus due to its potential to activate both innate and adaptive immunity, low toxicity to normal tissue, and long-term immune activity. However, its clinical effectiveness and large-scale application are limited due to the immunosuppression microenvironment, lack of spatiotemporal control, expensive cost, and long manufacturing time. Recently, nanomaterial combined engineered bacteria have emerged as a promising solution to the challenges of tumor immunotherapy, which offers spatiotemporal control, reversal of immunosuppression, and scalable production. Therefore, we summarize the latest research on nanomaterial-assisted engineered bacteria for precise tumor immunotherapies, including the cross-talk of nanomaterials and bacteria as well as their application in different immunotherapies. In addition, we further discuss the advantages and challenges of nanomaterial-engineered bacteria and their future prospects, inspiring more novel and intelligent tumor immunotherapy.

Despite significant advancements in chemotherapy, effective treatments for advanced cancer stages remain largely elusive due to chemoresistance. Resistance to anticancer agents in cancer cells can arise through various mechanisms, including multi-drug resistance, inhibition of apoptosis, modification of drug targets, and enhancement of DNA repair capabilities. Consequently, there is a critical need for agents that can suppress the molecular signatures responsible for drug resistance. Piperine, an active alkaloid extracted from Piper nigrum L. (black pepper), is one such agent that has been extensively studied for its potential in addressing chronic diseases, including cancer. Piperine's antineoplastic properties are mediated through the regulation of numerous key cellular signaling pathways and the modulation of various biological processes. Its capability to enhance drug bioavailability and counteract mechanisms of drug resistance, such as the inhibition of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1), emphasizes its potential as an adjunct in cancer therapy. Research across various cancer types has demonstrated piperine's role in chemosensitization by targeting P-gp and MRP-1 and altering drug-metabolizing enzymes. This review provides a comprehensive analysis of piperine's pharmacological characteristics and its capacity to modulate several cellular signaling pathways involved in drug resistance. Furthermore, the review emphasizes how piperine, when used in conjunction with other chemotherapeutic agents or natural compounds, can enhance therapeutic effects, leading to improved outcomes in cancer treatment., Competing Interests: Declaration of competing interest The authors claim no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

MicroRNAs, a collection of short noncoding RNAs, are promising biomarkers for identifying cancer in its early stages and tracking the effectiveness of treatment. This is due to their critical role in regulating gene expression and other vital biological functions via cell-level epigenetic mechanisms. This review brings together data on the molecular and clinical effects of miR-765 on different types of cancer. Significant variation in miR-765 levels has been observed in a variety of cancer types, suggesting that it could have an oncogene or tumor suppressor role. A number of pathways, including PLP2/Notch, VEGFA/Akt1, PDX1, KLK4, RUNX2, DPF3, EMP3, APE1, ERK/EMT axis, and others, are impacted by the inclusion of miR-765 in their analysis. MiR-765 is an essential biomarker that shows promise as a diagnostic tool for various types of cancer. The latest research has identified them as reliable predictive markers for detecting tumor development at an early stage. Based on our study, miR-765 shows promising potential as a biomarker for prognosis in multiple types of cancer. Specifically, we suggest that miR-765 could be an early detection marker for tumor development, progression, and metastasis., 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. Published by Elsevier B.V.)

Nanoparticle-mediated drug delivery offers a promising approach to targeted cancer therapy, leveraging the ability of nanoparticles to deliver therapeutic agents directly to cancerous tissues with minimal impact on surrounding healthy cells. The presence of these nanoparticles is governed by a concentration equation, which accounts for the diffusion, convection, and reaction of the nanoparticles with the blood components. It is well-known that whenever a disease or infection occurs in a human, in 80% of cases a rise in the concentration of hydrogen peroxide in the blood occurs. This is the reason why blood is assumed to contain hydrogen peroxide (in the present study), which is a biomarker of oxidative stress and inflammation. This study explores the integration of machine learning (ML) techniques into the optimization of drug delivery processes within the human cardiovascular system, focusing on the enhancement of these processes through the application of magnetic fields. By employing ML algorithms, we analyze and predict the behavior of nanoparticles as they navigate the complex fluid dynamics of the cardiovascular system, particularly under the influence of an external magnetic field. The predictive power of ML models enables the precise control of nanoparticle trajectories, optimizing their accumulation in cancerous tissues and improving the efficacy of the drug delivery system. The findings of this study demonstrate that ML-enhanced magnetic targeting can significantly enhance the precision and effectiveness of nanoparticle-mediated drug delivery, offering a new paradigm in cancer treatment strategies. This approach has the potential to revolutionize the field by providing personalized and highly efficient therapeutic solutions for cancer patients., (© 2024. The Author(s).)

Background: Wearable sensors are increasingly being explored in health care, including in cancer care, for their potential in continuously monitoring patients. Despite their growing adoption, significant challenges remain in the quality and consistency of data collected from wearable sensors. Moreover, preprocessing pipelines to clean, transform, normalize, and standardize raw data have not yet been fully optimized., Objective: This study aims to conduct a scoping review of preprocessing techniques used on raw wearable sensor data in cancer care, specifically focusing on methods implemented to ensure their readiness for artificial intelligence and machine learning (AI/ML) applications. We sought to understand the current landscape of approaches for handling issues, such as noise, missing values, normalization or standardization, and transformation, as well as techniques for extracting meaningful features from raw sensor outputs and converting them into usable formats for subsequent AI/ML analysis., Methods: We systematically searched IEEE Xplore, PubMed, Embase, and Scopus to identify potentially relevant studies for this review. The eligibility criteria included (1) mobile health and wearable sensor studies in cancer, (2) written and published in English, (3) published between January 2018 and December 2023, (4) full text available rather than abstracts, and (5) original studies published in peer-reviewed journals or conferences., Results: The initial search yielded 2147 articles, of which 20 (0.93%) met the inclusion criteria. Three major categories of preprocessing techniques were identified: data transformation (used in 12/20, 60% of selected studies), data normalization and standardization (used in 8/20, 40% of the selected studies), and data cleaning (used in 8/20, 40% of the selected studies). Transformation methods aimed to convert raw data into more informative formats for analysis, such as by segmenting sensor streams or extracting statistical features. Normalization and standardization techniques usually normalize the range of features to improve comparability and model convergence. Cleaning methods focused on enhancing data reliability by handling artifacts like missing values, outliers, and inconsistencies., Conclusions: While wearable sensors are gaining traction in cancer care, realizing their full potential hinges on the ability to reliably translate raw outputs into high-quality data suitable for AI/ML applications. This review found that researchers are using various preprocessing techniques to address this challenge, but there remains a lack of standardized best practices. Our findings suggest a pressing need to develop and adopt uniform data quality and preprocessing workflows of wearable sensor data that can support the breadth of cancer research and varied patient populations. Given the diverse preprocessing techniques identified in the literature, there is an urgency for a framework that can guide researchers and clinicians in preparing wearable sensor data for AI/ML applications. For the scoping review as well as our research, we propose a general framework for preprocessing wearable sensor data, designed to be adaptable across different disease settings, moving beyond cancer care., (©Bengie L Ortiz, Vibhuti Gupta, Rajnish Kumar, Aditya Jalin, Xiao Cao, Charles Ziegenbein, Ashutosh Singhal, Muneesh Tewari, Sung Won Choi. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 27.09.2024.)

Silks are a class of proteins generated naturally by different arthropods, including silkworms, spiders, scorpions, mites, wasps, and bees. This review discusses the silk fibroin and silk sericin fabricated by Bombyx mori silkworm as versatile fibers. This silk fiber is predominantly composed of hydrophobic silk fibroin and hydrophilic silk sericin. Fibroin is defined as a structural protein that bestows silk with strength, while sericin is characterized as a gum-like protein, tying the two fibrous proteins together and endowing silk proteins with elasticity. Due to their versatile structures, biocompatibility, and biodegradability, they could be tailored into intricate structures to warrant particular demands. The intrinsic functional groups of both proteins enable their functionalization and cross-linking with various biomaterials to endow the matrix with favorable antioxidant and antibacterial properties. Depending on the target applications, they can be integrated with other materials to formulate nanofibrous, hydrogels, films, and micro-nanoparticles. Given the outstanding biological and controllable physicochemical features of fibroin and sericin, they could be exploited in pharmaceutical applications involving tissue engineering, wound repair, drug delivery, and cancer therapy. This review comprehensively discusses the advancements in the implementation of different formulations of silk fibroin and sericin in wound healing and drug delivery systems, particularly 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 © 2024 Elsevier B.V. All rights reserved.)

Tumor suppressor genes and proto-oncogenes comprise most of the complex genomic landscape associated with cancer, with a minimal number of genes exhibiting dual-context-dependent functions. The transcription factor cellular promoter 2 (TFCP2), a pivotal transcription factor encoded by the alpha globin transcription factor CP2 gene, is a constituent of the TFCP2/grainyhead family of transcription factors. While grainyhead members have been extensively studied for their crucial roles in developmental processes, embryogenesis, and multiple cancers, the TFCP2 subfamily has been relatively less explored. The molecular mechanisms underlying TFCP2's involvement in carcinogenesis are still unclear even though it is a desirable target for cancer treatment and a therapeutic marker. This comprehensive literature review summarizes the molecular functions of TFCP2, emphasizing its involvement in cancer pathophysiology, particularly in the epithelial-mesenchymal transition and metastasis. It highlights TFCP2's critical function as a regulatory target and explores its potential as a prognostic marker for survival and inflammation in carcinomas. Its ambiguous association with carcinomas underlines the urgent need for an in-depth understanding to facilitate the development of more efficacious targeted therapeutic modality and diagnostic tools. This study aims to elucidate the multifaceted effects of TFCP2 regulation, through a comprehensive integration of the existing knowledge in cancer therapeutics. Furthermore, the clinical relevance and the inherent challenges encountered in investigating its intricate role in cancer pathogenesis have been discussed in this review., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The unique properties-such as biocompatibility, biodegradability, bio-absorbability, low cost, easy fabrication, and high versatility-have made polycaprolactone (PCL) the center of attraction for researchers. The derived introduction in this manuscript gives a pretty detailed overview of PCL, so you can first brush up on it. Discussion on the various PCL-based derivatives involves, but is not limited to, poly(ε-caprolactone-co-lactide) (PCL-co-LA), PCL-g-PEG, PCL-g-PMMA, PCL-g-chitosan, PCL-b-PEO, and PCL-g-PU specific properties and their probable applications in biomedicine. This paper has considered examining the differences in the diverse disease subtypes and the therapeutic value of using PCL. Advanced strategies for PCL in delivery systems are also considered. In addition, this review discusses recently patented products to provide a snapshot of recent updates in this field. Furthermore, the text probes into recent advances in PCL-based DDS, for example, nanoparticles, liposomes, hydrogels, and microparticles, while giving special attention to comparing the esters in the delivery of bioactive compounds such as anticancer drugs. Finally, we review future perspectives on using PCL in biomedical applications and the hurdles of PCL-based drug delivery, including fine-tuning mechanical strength/degradation rate, biocompatibility, and long-term effects in living systems., 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 B.V. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Gangliosides represent glycolipids containing sialic acid residues, present on the cell membrane with glycan residues exposed to the extracellular matrix (ECM), while the ceramides are anchored within the membrane. These molecules play a critical role in pathophysiological processes such as host-pathogen interactions, cell-cell recognition, signal transduction, cell adhesion, motility, and immunomodulation. Accumulated evidence suggests the overexpression of gangliosides on tumor tissues in comparison to healthy human tissues. These tumor-associated gangliosides have been implicated in various facets of tumor biology, including cell motility, differentiation, signaling, immunosuppression, angiogenesis, and metastasis. Consequently, these entities emerge as attractive targets for immunotherapeutic interventions. Notably, the administration of antibodies targeting gangliosides has demonstrated cytotoxic effects on cancer cells that exhibit an overexpression of these glycolipids. Passive immunotherapy approaches utilizing murine or murine/human chimeric anti-ganglioside antibodies have been explored as potential treatments for diverse cancer types. Additionally, vaccination strategies employing tumor-associated gangliosides in conjunction with adjuvants have entered the realm of promising techniques currently undergoing clinical trials. The present comprehensive review encapsulates the multifaceted roles of gangliosides in tumor initiation, progression, immunosuppression, and metastasis. Further, an overview is provided of the correlation between the expression status of gangliosides in normal and tumor cells and its impact on cancer patient survival. Furthermore, the discussion extends to ongoing and completed clinical trials employing diverse strategies to target gangliosides, elucidating their effectiveness in treating cancers. This emerging discipline is expected to supply substantial impetus for the establishment of novel therapeutic strategies., 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 Inc. All rights reserved.)

Despite considerable progress in cancer treatment options, resistance to chemotherapeutic drugs remains a significant challenge. This review focuses on Berberine (BBR), an isoquinoline alkaloid found in various medicinal plants, which has garnered attention in the field of oncology for its anticancer potential either alone or in combination with other compounds and its ability to modulate chemoresistance, acting as a natural chemosensitizer. BBR's ability to modulate chemoresistance is attributed to its diverse mechanisms of action, including inducing DNA breaks, inhibition of drug efflux pumps, modulation of apoptosis and necroptosis, downregulating multidrug resistance genes, enhancing immune response, suppressing angiogenesis and targeting multiple pathways within cancer cells, including protein kinase B/mammalian target of rapamycin (Akt/mTOR), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), poly(ADP-ribose) polymerase (PARP1), janus kinase/signal transducers and activators of transcription (JAK-STAT), Wnt/β-catenin etc. Moreover, BBR, in combination with other compounds, also offers a promising approach to cancer therapy, enforcing its broad-spectrum anticancer effects. Therefore, this review aims to elucidate the intricate mechanism of action of BBR in combinatorial therapy as a potential chemosensitizer to increase the efficiency of several drugs, including cisplatin, doxorubicin, lapatinib, tamoxifen, irinotecan, niraparib, etc. in various cancers. Additionally, this review briefly covers the origin and biological activities of BBR, exploring the specific actions underlying its anticancer effects. Further, pharmacokinetic properties of BBR are also discussed, providing insight into its therapeutic potential and optimization of its use in 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 © 2024 Elsevier B.V. All rights reserved.)

Interleukin-6 (IL-6), a pro-inflammatory cytokine, plays a crucial role in host immune defense and acute stress responses. Moreover, it modulates various cellular processes, including proliferation, apoptosis, angiogenesis, and differentiation. These effects are facilitated by various signaling pathways, particularly the signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). However, excessive IL-6 production and dysregulated signaling are associated with various cancers, promoting tumorigenesis by influencing all cancer hallmarks, such as apoptosis, survival, proliferation, angiogenesis, invasiveness, metastasis, and notably, metabolism. Emerging evidence indicates that selective inhibition of the IL-6 signaling pathway yields therapeutic benefits across diverse malignancies, such as multiple myeloma, prostate, colorectal, renal, ovarian, and lung cancers. Targeting key components of IL-6 signaling, such as IL-6Rs, gp130, STAT3, and JAK via monoclonal antibodies (mAbs) or small molecules, is a heavily researched approach in preclinical cancer studies. The purpose of this study is to offer an overview of the role of IL-6 and its signaling pathway in various cancer types. Furthermore, we discussed current preclinical and clinical studies focusing on targeting IL-6 signaling as a therapeutic strategy for various types of cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Biological nanoparticles, or bionanoparticles, are small molecules manufactured in living systems with complex production and assembly machinery. The products of the assembly systems can be further engineered to generate functionalities for specific purposes. These bionanoparticles have demonstrated advantages such as immune system evasion, minimal toxicity, biocompatibility, and biological clearance. Hence, bionanoparticles are considered the new paradigm in nanoscience research for fabricating safe and effective nanoformulations for therapeutic purposes. Harnessing the power of the immune system to recognize and eradicate malignancies is a viable strategy to achieve better therapeutic outcomes with long-term protection from disease recurrence. However, cancerous tissues have evolved to become invisible to immune recognition and to transform the tumor microenvironment into an immunosuppressive dwelling, thwarting the immune defense systems and creating a hospitable atmosphere for cancer growth and progression. Thus, it is pertinent that efforts in fabricating nanoformulations for immunomodulation are mindful of the tumor-induced immune aberrations that could render cancer nanotherapy inoperable. This review systematically categorizes the immunosuppression mechanisms, the regulatory immunosuppressive cellular players, and critical suppressive molecules currently targeted as breakthrough therapies in the clinic. Finally, this review will summarize the engineering strategies for affording immune moderating functions to bionanoparticles that tip the tumor microenvironment (TME) balance toward cancer elimination, a field still in the nascent stage.

A comprehensive model of chemotherapy treatment of cancer can help us to optimize the drug administration/dosage and improve the treatment outcome. In the present study, a multiscale mathematical model of tumor growth during chemotherapy treatment is developed to predict its response to the medication and cancer progression. The modeling is a continuous multiscale simulation consisting of three tissue phases including cancer cells, normal cells, and extracellular matrix. In addition to the drug administration, the impacts of immune cells, programmed cell death, nutrient competition, and glucose concentration are included. The outputs of our mathematical model conform to the published experimental and clinical data, and it can be used in optimizing chemotherapy, and personalized cancer treatment.

Cancer is the result of genetic abnormalities that cause normal cells to grow into neoplastic cells. Cancer is characterized by several distinct features, such as uncontrolled cell growth, extensive spreading to other parts of the body, and the ability to resist treatment. The scientists have stressed the development of nanostructures as novel therapeutic options in suppressing cancer, in response to the emergence of resistance to standard medicines. One of the specific mechanisms with dysregulation during cancer is autophagy. Nanomaterials have the ability to specifically carry medications and genes, and they can also enhance the responsiveness of tumor cells to standard therapy while promoting drug sensitivity. The primary mechanism in this process relies on autophagosomes and their fusion with lysosomes to break down the components of the cytoplasm. While autophagy was initially described as a form of cellular demise, it has been demonstrated to play a crucial role in controlling metastasis, proliferation, and treatment resistance in human malignancies. The pharmacokinetic profile of autophagy modulators is poor, despite their development for use in cancer therapy. Consequently, nanoparticles have been developed for the purpose of delivering medications and autophagy modulators selectively and specifically to the cancer process. Furthermore, several categories of nanoparticles have demonstrated the ability to regulate autophagy, which plays a crucial role in defining the biological characteristics and response to therapy of tumor cells., 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., (Published by Elsevier B.V.)

Tumors produce a hypoxic environment that greatly influences cancer treatment, and conventional chemotherapeutic drugs cannot selectively accumulate in the tumor region because of the lack of a tumor targeting mechanism, causing increased systemic toxicities and side effects. Hence, designing and developing new nanoplatforms that combine multimodal therapeutic regimens is essential to improve tumor therapeutic efficacy. Herein, we report the synthesis of ultrafine Cu nanoparticles loaded with a drug combination of cisplatin (Pt) and 1-methyl-d-tryptophan (1-MT) and externally coated with 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer, polydopamine (PDA) and CaO 2 of MIL-101(Fe) as a new nanoplatform (Cu@MIL-101@PMTPC). The nanoplatform synergistically combined chemodynamic therapy (CDT), photodynamic therapy (PDT), and immunochemotherapy. The Fe 3+ in MIL-101(Fe) and the surface Cu nanoparticles exhibited strong ability to consume intracellular glutathione (GSH), thereby generating a Fenton-like response in the tumor microenvironment (TME) with substantial peroxidase (POD)-like and superoxide dismutase (SOD)-like activities. In this design, we used the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-MT to overcome chemotherapy-induced immune escape phenomena including enhanced CD8 + and CD4 + T cell expression, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production, and accelerated immunogenic cell death. The targeted release of cisplatin loaded into Cu@MIL-101@PMTPC also reduced toxic side effects of chemotherapy. TCPP generated a large amount of singlet oxygen ( 1 O 2 ) upon specific laser irradiation to effectively kill tumor cells. CaO 2 on the outer layer generated oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ) to ameliorate hypoxia in the tumor microenvironment, enhance the PDT effect, and provide a continuous supply of H 2 O 2 for the Fenton-like reaction. Thus, this nanocarrier platform exhibited a powerful chemodynamic, photodynamic, and immunochemotherapeutic cascade, providing a new strategy 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 © 2024 Elsevier Inc. All rights reserved.)

The application of three- and four-dimensional (3D/4D) printing in cancer research represents a significant advancement in understanding and addressing the complexities of cancer biology. 3D/4D materials provide more physiologically relevant environments compared to traditional two-dimensional models, allowing for a more accurate representation of the tumor microenvironment that enables researchers to study tumor progression, drug responses, and interactions with surrounding tissues under conditions similar to in vivo conditions. The dynamic nature of 4D materials introduces the element of time, allowing for the observation of temporal changes in cancer behavior and response to therapeutic interventions. The use of 3D/4D printing in cancer research holds great promise for advancing our understanding of the disease and improving the translation of preclinical findings to clinical applications. Accordingly, this review aims to briefly discuss 3D and 4D printing and their advantages and limitations in the field of cancer. Moreover, new techniques such as 5D/6D printing and artificial intelligence (AI) are also introduced as methods that could be used to overcome the limitations of 3D/4D printing and opened promising ways for the fast and precise diagnosis and treatment of cancer.

Tumor heterogeneity and drug resistance have been invincible features of cancer for its complete cure. Despite the advent of immunotherapy, the expansion and diversification of cancer cells evolved even in the absence or presence of drug treatment discourage additional therapeutic interventions. For the eradication of cancer cells, therefore, an 'all-at-once' strategy is required, which exploits both target-selective chemotherapy and non-selective physicotherapy. Multifactorial microcapsules comprising gold nanoparticles (AuNPs) and a self-assembly protein of α-synuclein (αS) were fabricated, in which hydrophobic and hydrophilic drugs could be separately encapsulated by employing lipid-based inverted micelles (IMs). Their combined physico-chemical therapeutic effects were examined since they also contained both membrane-disrupting IMs and heat-generating AuNPs upon irradiation as physicotherapeutic agents. For the optimal enclosure of IMs containing hydrophilic drugs, a porous inner skeleton made of poly(lactic-co-glycolic acid) was introduced, which would play the roles of not only compartmentalizing the internal space but also enhancing proteolytic disintegration of the microcapsules to discharge and stabilize IMs to the outside. In fact, hydrophobic paclitaxel and hydrophilic doxorubicin showed markedly enhanced drug efficacy when delivered in the IM-containing microcapsules exhibiting the 'quantal' release of both drugs into the cells whose integrity could be also affected by the IMs. In addition, the remnants of αS-AuNP microcapsules produced via proteolysis also caused cell death through photothermal effect. The multifactorial microcapsules are therefore considered as a promising anti-cancer drug carrier capable of performing combinatorial selective and non-selective chemical and physical therapies to overcome tumor heterogeneity and drug resistance., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Cancer has become a burgeoning global healthcare concern marked by its exponential growth and significant economic ramifications. Though advancements in the treatment modalities have increased the overall survival and quality of life, there are no definite treatments for the advanced stages of this malady. Hence, understanding the diseases etiologies and the underlying molecular complexities, will usher in the development of innovative therapeutics. Recently, YAP/TAZ transcriptional regulation has been of immense interest due to their role in development, tissue homeostasis and oncogenic transformations. YAP/TAZ axis functions as coactivators within the Hippo signaling cascade, exerting pivotal influence on processes such as proliferation, regeneration, development, and tissue renewal. In cancer, YAP is overexpressed in multiple tumor types and is associated with cancer stem cell attributes, chemoresistance, and metastasis. Activation of YAP/TAZ mirrors the cellular "social" behavior, encompassing factors such as cell adhesion and the mechanical signals transmitted to the cell from tissue structure and the surrounding extracellular matrix. Therefore, it presents a significant vulnerability in the clogs of tumors that could provide a wide window of therapeutic effectiveness. Natural compounds have been utilized extensively as successful interventions in the management of diverse chronic illnesses, including cancer. Owing to their capacity to influence multiple genes and pathways, natural compounds exhibit significant potential either as adjuvant therapy or in combination with conventional treatment options. In this review, we delineate the signaling nexus of YAP/TAZ axis, and present natural compounds as an alternate strategy to target 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 © 2024. Published by Elsevier Ltd.)

Cancer remains one of the global leading causes of death and various vaccines have been developed over the years against it, including cell-based, nucleic acid-based, and viral-based cancer vaccines. Although many vaccines have been effective in in vivo and clinical studies and some have been FDA-approved, there are major limitations to overcome: (1) developing one universal vaccine for a specific cancer is difficult, as tumors with different antigens are different for different individuals, (2) the tumor antigens may be similar to the body's own antigens, and (3) there is the possibility of cancer recurrence. Therefore, developing personalized cancer vaccines with the ability to distinguish between the tumor and the body's antigens is indispensable. This paper provides a comprehensive review of different types of cancer vaccines and highlights important factors necessary for developing efficient cancer vaccines. Moreover, the application of other technologies in cancer therapy is discussed. Finally, several insights and conclusions are presented, such as the possibility of using cold plasma and cancer stem cells in developing future cancer vaccines, to tackle the major limitations in the cancer vaccine developmental process.

This study introduces an innovative detection system for multiple cancer biomarkers, employing transcription isothermal amplification methods in conjunction with a tetrahedral DNA nanostructure (TDN). We demonstrate that TDN enhances various transcription isothermal amplification methods by placing DNA probes in proximity. Notably, the TDN-enhanced split T7 promoter-based isothermal transcription amplification with light-up RNA aptamer (STAR) system stands out for its optimal performance and operational simplicity, especially in identifying non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs). Multiplex detection of lncRNAs was also achieved by generating distinct light-up RNA aptamers, each emitting unique fluorescence signals. The system effectively identified the target lncRNAs, demonstrating high sensitivity and selectivity in both cell lines and clinical samples. The system, utilizing the single enzyme T7 RNA polymerase, can be easily tailored for alternative targets by substituting target-specific sequences in DNA probes and seamlessly integrated with other isothermal amplification methods for greater sensitivity and accuracy in the detection of multiple cancer biomarkers., 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 B.V. All rights reserved.)

Disruptions in metal balance can trigger a synergistic interplay of cuproptosis and ferroptosis, offering promising solutions to enduring challenges in oncology. Here, we have engineered a Cellular Trojan Horse, named MetaCell, which uses live neutrophils to stably internalize thermosensitive liposomal bimetallic Fe-Cu MOFs (Lip@Fe-Cu-MOFs). MetaCell can instigate cuproptosis and ferroptosis, thereby enhancing treatment efficacy. Mirroring the characteristics of neutrophils, MetaCell can evade the immune system and not only infiltrate tumors but also respond to inflammation by releasing therapeutic components, thereby surmounting traditional treatment barriers. Notably, Lip@Fe-Cu-MOFs demonstrate notable photothermal effects, inciting a targeted release of Fe-Cu-MOFs within cancer cells and amplifying the synergistic action of cuproptosis and ferroptosis. MetaCell has demonstrated promising treatment outcomes in tumor-bearing mice, effectively eliminating solid tumors and forestalling recurrence, leading to extended survival. This research provides great insights into the complex interplay between copper and iron homeostasis in malignancies, potentially paving the way for innovative approaches in cancer treatment.

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with BCR, which are essential for stimulating B cell antigen presentation-mediated B/CD4 T cell crosstalk in vitro and in vivo . ACNVax, combined with anti-PD-1, achieved long-term tumor remission (>200 days) with 80% complete response in mice with HER2 + breast cancer. ACNVax not only remodeled the tumor immune microenvironment but also induced a long-term immune memory, as evidenced by complete rejection of tumor rechallenge and a high level of antigen-specific memory B, CD4, and CD8 cells in mice (>200 days). This study provides a cancer vaccine design strategy, using B/CD4 T cell epitopes in an antigen clustered topography, to achieve long-term durable anticancer efficacy through promoting B/CD4 T cell crosstalk.

Acute lymphoblastic leukemia (ALL), a hematologic cancer that involves the production of abnormal lymphoid precursor cells, primarily affects children aged 2 to 10 years. The bacterial enzyme L-asparaginase produced from Escherichia coli is utilised as first-line therapy, despite the fact that 30 % of patients have a treatment-limiting hypersensitivity reaction. The current study elucidates the biosynthesis of extremely stable, water-dispersible, anisotropic silver nanoparticles (ANI Ag NPs) at room temperature and investigation of its anti-tumor potency in comparison to L-asparaginase. The optical, morphological, compositional, and structural properties of synthesized nanoparticles were evaluated using UV-Vis-NIR spectroscopy, Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy, and X-ray Diffractometer. The UV-Vis-NIR spectra revealed the typical Surface Plasmon Resonance (SPR) at 423 nm along with additional NIR absorption at 962 nm and 1153 nm, while TEM images show different shapes and sizes of Ag nanoparticles ranging from 6.81 nm to 46 nm, together confirming their anisotropic nature. Further, the MTT assay demonstrated promising anticancer effects of ANI Ag NPs with an IC 50 value of ∼7 μg/mL against HuT-78 cells. These sustainable anisotropic silver nanoparticles exhibited approximately four times better cytotoxic ability (at and above 10 μg/mL concentrations) than L-asparaginase against HuT-78 cells (a human T lymphoma cell line). Apoptosis analysis by Wright-Geimsa, Annexin-V, and DAPI staining indicated the role of apoptosis in ANI Ag NPs-mediated cell death. The measurement of NO, and Bcl2 and cleaved caspase-3 levels by colorimetric method and immunoblotting, respectively suggested their involvement in ANI Ag NPs-elicited apoptosis. The findings indicate that the biogenic approach proposed herein holds tremendous promise for the rapid and straightforward design of novel multifunctional nanoparticles for the treatment of T cell malignancies., 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. Published by Elsevier B.V.)

Despite the crucial role of lymphangiogenesis during development and in several diseases with implications for tissue regeneration, immunity, and cancer, there are significantly fewer tools to understand this process relative to angiogenesis. While there has been a major surge in modeling angiogenesis with microphysiological systems, they have not been rigorously optimized or standardized to enable the recreation of the dynamics of lymphangiogenesis. Here, a Lymphangiogenesis-Chip (L-Chip) is engineered, within which new sprouts form and mature depending upon the imposition of interstitial flow, growth factor gradients, and pre-conditioning of endothelial cells with growth factors. The L-Chip reveals the independent and combinatorial effects of these mechanical and biochemical determinants of lymphangiogenesis, thus ultimately resulting in sprouts emerging from a parent vessel and maturing into tubular structures up to 1 mm in length within 4 days, exceeding prior art. Further, when the constitution of the pre-conditioning cocktail and the growth factor cocktail used to initiate and promote lymphangiogenesis are dissected, it is found that endocan (ESM-1) results in more dominant lymphangiogenesis relative to angiogenesis. Therefore, The L-Chip provides a foundation for standardizing the microfluidics assays specific to lymphangiogenesis and for accelerating its basic and translational science at par with angiogenesis., (© 2024 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)

Heterocyclic compounds containing 1,2,3-triazole and isatin as core structures have emerged as promising drug candidates due to their diverse biological activities such as anti-cancer, antifungal, antimicrobial, antitumor, anti-epileptic, antiviral, and more. The presence of 1,2,3-triazoles and isatin heterocycles in these hybrids, both individually known for their medicinal significance, has increasingly piqued the interest of drug discovery researchers, as they seek to delve deeper into their extensive pharmacological potential for enhancing therapeutic efficacy. Moreover, these hybrid compounds are synthetically accessible using readily available materials. Therefore, there is a pressing need to provide a comprehensive overview of the existing knowledge in this field, offering valuable insights to readers and paving the way for the discovery of novel 1,2,3-triazole-linked isatin hybrids with therapeutic potential., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Bacteremia refers to the presence of bacteria in the bloodstream, which can lead to a serious and potentially life-threatening condition. In oncology patients, individuals undergoing cancer treatment have a higher risk of developing bacteremia due to a weakened immune system resulting from the disease itself or the treatments they receive. Prompt and accurate detection of bacterial infections and monitoring the effectiveness of antibiotic therapy are essential for enhancing patient outcomes and preventing the development and dissemination of multidrug-resistant bacteria. Traditional methods of infection monitoring, such as blood cultures and clinical observations, are time-consuming, labor-intensive, and often subject to limitations. This manuscript presents an innovative application of infrared spectroscopy of leucocytes of pediatric oncology patients with bacteremia combined with machine learning to diagnose the etiology of infection as bacterial and simultaneously monitor the efficacy of the antibiotic therapy in febrile pediatric oncology patients with bacteremia infections. Through the implementation of effective monitoring, it becomes possible to promptly identify any indications of treatment failure. This, in turn, indirectly serves to limit the progression of antibiotic resistance. The logistic regression (LR) classifier was able to differentiate the samples as bacterial or control within an hour, after receiving the blood samples with a success rate of over 95 %. Additionally, initial findings indicate that employing infrared spectroscopy of white blood cells (WBCs) along with machine learning is viable for monitoring the success of antibiotic therapy. Our follow up results demonstrate an accuracy of 87.5 % in assessing the effectiveness of the antibiotic 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 © 2024 Elsevier B.V. All rights reserved.)

Optical coherence tomography (OCT) imaging mainly uses backscattered light to visualize the structural and functional information on biological tissues. In particular, OCT angiography can not only map the capillary networks but also capture the blood flow in the tissue microenvironment, making it a good candidate for neuroimaging and tumor imaging in vivo and in real time. To further improve the detection accuracy of cancer or brain disorders, it is essential to develop a natural and nontoxic contrast agent for enhanced OCT imaging in the second near-infrared (NIR-II) window. In this study, a superior biocompatible and highly scattering NIR-II fat nanoemulsion was constructed to improve OCT imaging contrast and depth for monitoring the vascular network changes of the cerebral cortex or tumor. In vivo experimental results demonstrated that a natural fat nanoemulsion can serve as an excellent probe for enhanced OCT neuroimaging and tumor imaging.

Tumor whole cell, carrying a complete set of tumor-associated antigens and tumor-specific antigens, has shown great potential in the construction of tumor vaccines but is hindered by the complex engineering means and limited efficacy to cause immunity. Herein, we provided a strategy for the self-mineralization of autologous tumor cells with palladium ions in microfluidic droplets, which endowed the engineered cells with both immune and catalytic functions, to establish a bioorthogonally catalytic tumor whole-cell vaccine. This vaccine showed strong inhibition both in the occurrence and recurrence of tumor by invoking the immediate antitumor immunity and building a long-term immunity.

Unlike normal cells, cancer cells frequently exhibit supernumerary centrosomes, leading to formation of multipolar spindles that can trigger cell death. Nevertheless, cancer cells with supernumerary centrosomes escape the deadly consequences of unequal segregation of genomic material by coalescing their centrosomes into two poles. This unique trait of cancer cells presents a promising target for cancer therapy, focusing on selectively attacking cells with supernumerary centrosomes. Nek2A is a kinase involved in mitotic regulation, including the centrosome cycle, where it phosphorylates linker proteins to separate centrosomes. In this study, we investigated if Nek2A also prevents clustering of supernumerary centrosomes, akin to its separation function. Reduction of Nek2A activity, achieved through knockout, silencing, or inhibition, promotes centrosome clustering, whereas its overexpression results in inhibition of clustering. Significantly, prevention of centrosome clustering induces cell death, but only in cancer cells with supernumerary centrosomes, both in vitro and in vivo. Notably, none of the known centrosomal (e.g., CNAP1, Rootletin, Gas2L1) or non-centrosomal (e.g., TRF1, HEC1) Nek2A targets were implicated in this machinery. Additionally, Nek2A operated via a pathway distinct from other proteins involved in centrosome clustering mechanisms, like HSET and NuMA. Through TurboID proximity labeling analysis, we identified novel proteins associated with the centrosome or microtubules, expanding the known interaction partners of Nek2A. KIF2C, in particular, emerged as a novel interactor, confirmed through coimmunoprecipitation and localization analysis. The silencing of KIF2C diminished the impact of Nek2A on centrosome clustering and rescued cell viability. Additionally, elevated Nek2A levels were indicative of better patient outcomes, specifically in those predicted to have excess centrosomes. Therefore, while Nek2A is a proposed target, its use must be specifically adapted to the broader cellular context, especially considering centrosome amplification. Discovering partners such as KIF2C offers fresh insights into cancer biology and new possibilities for targeted treatment., (© 2024. The Author(s).)

The breast cancer tumor microenvironment (TME) is dynamic, with various immune and non-immune cells interacting to regulate tumor progression and anti-tumor immunity. It is now evident that the cells within the TME significantly contribute to breast cancer progression and resistance to various conventional and newly developed anti-tumor therapies. Both immune and non-immune cells in the TME play critical roles in tumor onset, uncontrolled proliferation, metastasis, immune evasion, and resistance to anti-tumor therapies. Consequently, molecular and cellular components of breast TME have emerged as promising therapeutic targets for developing novel treatments. The breast TME primarily comprises cancer cells, stromal cells, vasculature, and infiltrating immune cells. Currently, numerous clinical trials targeting specific TME components of breast cancer are underway. However, the complexity of the TME and its impact on the evasion of anti-tumor immunity necessitate further research to develop novel and improved breast cancer therapies. The multifaceted nature of breast TME cells arises from their phenotypic and functional plasticity, which endows them with both pro and anti-tumor roles during tumor progression. In this review, we discuss current understanding and recent advances in the pro and anti-tumoral functions of TME cells and their implications for developing safe and effective therapies to control breast cancer progress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Akinsipe, Mohamedelhassan, Akinpelu, Pondugula, Mistriotis, Avila and Suryawanshi.)

A chemo-drug such as cisplatin is effective for cancer treatment but remains non-specific, is susceptible to drug resistance, and induces several side effects on organ systems. Zeolitic imidazolate framework-8, a type of MOF, has gained attention, including as a drug delivery method for targeted cancer therapeutics. In this study, ZIF-8/Silica nanocomposite was synthesized using a one-pot hydrothermal technique using the Stober technique. We studied the effect of phyto-synthesized GPt and chemo-drug cisplatin CPt on ZIF-8/Silica for targeted efficacy of cancer therapy. The texture, morphology, and chemical environment of Pt on ZIF-8/Silica were analyzed using different characterization techniques such as XRD, FT-IR, BET, diffuse reflectance spectroscopy, SEM-EDX, TEM, zeta potential, and TGA analysis. The isothermal behavior of CPt and GPt adsorption was investigated using isotherm models like Langmuir, Freundlich, and Temkin isotherm. The adsorption kinetics indicating the adsorption efficiency of GPt and CPt are influenced by the concentration of Pt complex and the adsorption sites of ZIF-8/Silica. A high entrapment efficiency and loading capacity of GPt (86% and 4.3%) and CPt (91% and 4.5%) were evident on ZIF-8/Silica. The nanocomposite showed a pH-sensitive Pt release using a dialysis membrane technique. For instance, a high release of GPt (93%) was observed under pH = 6.6 in 72 h, while the release reduced to 50% at pH 7.4 in 72 h. The anti-cancer activity of nanoformulations was studied in vitro using MCF7 (breast cancer cells) and HFF-1 (human foreskin fibroblast) cells. The findings demonstrated that GPt is as effective as CPt; the EC50 value for MCF7 cells treated with ZIF-8/Silica/Cp/PEG was 94.86 µg/mL, whereas for ZIF-8/Silica/GPt/PEG it was 60.19 µg/mL.

Context: Social determinants of health (SDOH) impact population health. Leveraging community-level strengths related to SDOH through a social infrastructure perspective can optimize health behaviors and health outcomes to promote health equity., Objective: Our aims were to develop, validate, and apply the Connected Community Classification (C3) as comprehensive community-level measure of protective SDOH and structural factors in the Four Corners states region of the United States., Design: C3 was developed using an iterative principal component analysis of publicly available data mapped to 5 SDOH domains. Regional clustering of C3 by zip code tabulation area (ZCTA) was identified using spatial autocorrelation methods., Main Outcomes: In adjusted spatial autoregressive models, we analyzed the association of C3 with high-risk health behaviors and chronic disease prevalence using publicly available data for population-level estimates of fruit and vegetable intake, physical activity, obesity, smoking, alcohol use, coronary heart disease (CHD), diabetes, and cancer., Results: C3 was found to be reliable and valid; a C3 value of 10 indicates communities with greater connection (high), while a value of 1 indicates communities with greater separation (low) to social infrastructure. Lower connection, as measured by C3, was significantly inversely associated with lower fruit and vegetable intake, lower physical activity, and higher rates of obesity, smoking, CHD, diabetes, and cancer. C3 was significantly positively associated with heavy alcohol use., Conclusions: These findings demonstrate that communities connected to social infrastructure have better population health outcomes. C3 captures protective community attributes and can be used in future applications to assist health researchers, practitioners, nonprofits, and policymakers to advance social connection and health equity in geographically diverse underserved regions., Competing Interests: The authors declare no conflict of interest. The sponsor had no role in the design, execution, interpretation, or writing of the study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Recent advances have brought forth the complex interplay between tumor cell plasticity and its consequential impact on drug resistance and tumor recurrence, both of which are critical determinants of neoplastic progression and therapeutic efficacy. Various forms of tumor cell plasticity, instrumental in facilitating neoplastic cells to develop drug resistance, include epithelial-mesenchymal transition (EMT) alternatively termed epithelial-mesenchymal plasticity, the acquisition of cancer stem cell (CSC) attributes, and transdifferentiation into diverse cell lineages. Nuclear receptors (NRs) are a superfamily of transcription factors (TFs) that play an essential role in regulating a multitude of cellular processes, including cell proliferation, differentiation, and apoptosis. NRs have been implicated to play a critical role in modulating gene expression associated with tumor cell plasticity and drug resistance. This review aims to provide a comprehensive overview of the current understanding of how NRs regulate these key aspects of cancer biology. We discuss the diverse mechanisms through which NRs influence tumor cell plasticity, including EMT, stemness, and metastasis. Further, we explore the intricate relationship between NRs and drug resistance, highlighting the impact of NR signaling on chemotherapy, radiotherapy and targeted therapies. We also discuss the emerging therapeutic strategies targeting NRs to overcome tumor cell plasticity and drug resistance. This review also provides valuable insights into the current clinical trials that involve agonists or antagonists of NRs modulating various aspects of tumor cell plasticity, thereby delineating the potential of NRs as therapeutic targets for improved cancer treatment outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chemotherapy is one of the most efficient methods for treating cancer patients. Chemotherapy aims to eliminate cancer cells as thoroughly as possible. Delivering medications to patients' bodies through various methods, either oral or intravenous is part of the chemotherapy process. Different cell-kill hypotheses take into account the interactions of the expansion of the tumor volume, external drugs, and the rate of their eradication. For the control of drug usage and tumor volume, a model based smooth super-twisting control (MBSSTC) is proposed in this paper. Firstly, three nonlinear cell-kill mathematical models are considered in this work, including the log-kill, Norton-Simon, and E max hypotheses subject to parametric uncertainties and exogenous perturbations. In accordance with clinical recommendations, the tumor volume follows a predefined trajectory after chemotherapy. Secondly, the MBSSTC is applied for the three cell-kill models to attain accurate trajectory tracking even in the presence of uncertainties and disturbances. Compared to conventional super-twisting control (STC), the non-smooth term is introduced in the proposed control to enhance the anti-disturbance capability. Finally, simulation comparisons are performed across the proposed MBSSTC, conventional STC, and proportional-integral (PI) control methods to show the effectiveness and merits of our designed control method., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Precise mapping and regulation of cell surface receptors hold immense significance in disease treatment, such as cancer, infection, and neurodisorders, but also face enormous challenges. In this study, we designed a series of adjustable multivalent aptamer-based DNA nanostructures to precisely control their interaction with receptors in tumor cells. By profiling surface receptors on 12 cell lines using 10 different aptamers, we generated a heatmap that accurately distinguished between various tumor types based on multiple markers. We then incorporated these aptamers onto DNA origami structures to regulate receptor recognition, with patch-like structures demonstrating a tendency to be trapped on the cell surface and with tube-like structures showing a preference for internalization. Through precise control of aptamer species, valence, and geometric patterns, we found that multiheteroreceptor-mediated recognition not only favored the specific binding of nanostructures to tumor cells but also greatly enhanced intracellular uptake by promoting clathrin-dependent endocytosis. Specifically, we achieved over 5-fold uptake in different tumor cells versus normal cells using tube-like structures modified with different diheteroaptamer pairs, facilitating targeted drug delivery. Moreover, patch-like structures with triheteroaptamers guided specific interactions between macrophages and tumor cells, leading to effective immune clearance. This programmable multivalent system allows for the precise regulation of cell recognition using multiple parameters, demonstrating great potential for personalized tumor treatment.

Medical diagnosis through prediction and analysis is par excellence in integrating modern technologies such as the Internet of Things (IoT). With the aid of such technologies, clinical assessments are eased with protracted computing. Specifically, cancer research through structure prediction and analysis is improved through human and machine interventions sustaining precision improvements. This article, therefore, introduces a Protein Structure Prediction Technique based on Three-Dimensional Sequence. This sequence is modeled using amino acids and their folds observed during the pre-initial cancer stages. The observed sequences and the inflammatory response score of the structure are used to predict the impact of cancer. In this process, ensemble learning is used to identify sequence and folding responses to improve inflammations. This score is correlated with the clinical data for structures and their folds independently for determining the structure changes. Such changes through different sequences are handled using repeated ensemble learning for matching and unmatching response scores. The introduced idea integrated with deep ensemble learning and IoT combination, notably employing stacking method for enhanced cancer prediction precision and interdisciplinary collaboration. The proposed technique improves prediction precision, data correlation, and change detection by 11.83%, 8.48%, and 13.23%, respectively. This technique reduces correlation time and complexity by 10.43% and 12.33%, respectively., (© 2024. The Author(s).)

Rationale: Cancer treatment outcome is traditionally evaluated by tumor volume change in clinics, while tumor microvascular heterogeneity reflecting tumor response has not been fully explored due to technical limitations. Methods: We introduce a new paradigm in super-resolution ultrasound imaging, termed pattern recognition of microcirculation (PARM), which identifies both hemodynamic and morphological patterns of tumor microcirculation hidden in spatio-temporal space trajectories of microbubbles. Results: PARM demonstrates the ability to distinguish different local blood flow velocities separated by a distance of 24 μm. Compared with traditional vascular parameters, PARM-derived heterogeneity parameters prove to be more sensitive to microvascular changes following anti-angiogenic therapy. Particularly, PARM-identified "sentinel" microvasculature, exhibiting evident structural changes as early as 24 hours after treatment initiation, correlates significantly with subsequent tumor volume changes (|r| > 0.9, P < 0.05). This provides prognostic insight into tumor response much earlier than clinical criteria. Conclusions: The ability of PARM to noninvasively quantify tumor vascular heterogeneity at the microvascular level may shed new light on early-stage assessment of cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Far infrared (FIR) irradiation is commonly used as a convenient, non-contact, non-invasive treatment for diseases such as myocardial ischemia, diabetes, and chronic kidney disease. In this review, we focus on reviewing the potential therapeutic mechanisms of FIR and its cutting-edge applications in cancer detection. Firstly, we searched the relevant literature in the last decade for systematic screening and briefly summarized the biophysical properties of FIR. We then focused on the possible mechanisms of FIR in wound healing, cardiovascular diseases, and other chronic diseases. In addition, we review recent applications of FIR in cancer detection, where Fourier transform infrared spectroscopy and infrared thermography provide additional diagnostic methods for the medical diagnosis of cancer. Finally, we conclude and look into the future development of FIR for disease treatment and cancer detection. As a high-frequency non-ionizing wave, FIR has the advantages of safety, convenience, and low cost. We hope that this review can provide biological information reference and relevant data support for those who are interested in FIR and related high-frequency non-ionizing waves, to promote the further application of FIR in the biomedical field., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Three-dimensional (3D) cell cultures have emerged as valuable tools in cancer research, offering significant advantages over traditional two-dimensional (2D) cell culture systems. In 3D cell cultures, cancer cells are grown in an environment that more closely mimics the 3D architecture and complexity of in vivo tumors. This approach has revolutionized cancer research by providing a more accurate representation of the tumor microenvironment (TME) and enabling the study of tumor behavior and response to therapies in a more physiologically relevant context. One of the key benefits of 3D cell culture in cancer research is the ability to recapitulate the complex interactions between cancer cells and their surrounding stroma. Tumors consist not only of cancer cells but also various other cell types, including stromal cells, immune cells, and blood vessels. These models bridge traditional 2D cell cultures and animal models, offering a cost-effective, scalable, and ethical alternative for preclinical research. As the field advances, 3D cell cultures are poised to play a pivotal role in understanding cancer biology and accelerating the development of effective anticancer therapies. This review article highlights the key advantages of 3D cell cultures, progress in the most common scaffold-based culturing techniques, pertinent literature on their applications in cancer research, and the ongoing challenges., (© 2024. The Author(s).)

Valosin-containing protein (VCP)/p97, an AAA+ ATPase critical for maintaining proteostasis, emerges as a promising target for cancer therapy. This study reveals that targeting VCP selectively eliminates breast cancer cells while sparing non-transformed cells by inducing paraptosis, a non-apoptotic cell death mechanism characterized by endoplasmic reticulum and mitochondria dilation. Intriguingly, oncogenic HRas sensitizes non-transformed cells to VCP inhibition-mediated paraptosis. The susceptibility of cancer cells to VCP inhibition is attributed to the non-attenuation and recovery of protein synthesis under proteotoxic stress. Mechanistically, mTORC2/Akt activation and eIF3d-dependent translation contribute to translational rebound and amplification of proteotoxic stress. Furthermore, the ATF4/DDIT4 axis augments VCP inhibition-mediated paraptosis by activating Akt. Given that hyperactive Akt counteracts chemotherapeutic-induced apoptosis, VCP inhibition presents a promising therapeutic avenue to exploit Akt-associated vulnerabilities in cancer cells by triggering paraptosis while safeguarding normal cells., (© 2024. The Author(s).)

Tumor-derived extracellular vesicles (TDEs) have potential for therapeutic cancer vaccine applications since they innately possess tumor-associated antigens, mediate antigen presentation, and can incorporate immune adjuvants for enhanced vaccine efficacy. However, the original TDEs also contain immune-suppressive proteins. To address this, we proposed a simple yet powerful preconditioning method to improve the overall immunogenicity of the TDEs. This approach involved inducing endoplasmic reticulum (ER) stress on parental tumor cells via N-glycosylation inhibition with tunicamycin. The generated immunogenic TDEs (iTDEs) contained down-regulated immunosuppressive proteins and up-regulated immune adjuvants, effectively activating dendritic cells (DCs) in vitro . Furthermore, in vivo evidence from a tumor-bearing mouse model showed that iTDEs activated DCs, enabling cytotoxic T lymphocytes (CTLs) to target tumors, and eventually established a systemic antitumor immune response. Additionally, iTDEs significantly delayed tumor recurrence in a postsurgery model compared with control groups. These findings highlight the immense potential of our strategy for utilizing TDEs to develop effective cancer vaccines.