Enhance Cancer Treatment Research Articles

Targeting endocytosis to sensitize cancer cells to programmed cell death.

Evading programmed cell death (PCD) is a hallmark of cancer that allows tumor cells to survive and proliferate unchecked. Endocytosis, the process by which cells internalize extracellular materials, has emerged as a key regulator of cell death pathways in cancer. Many tumor types exhibit dysregulated endocytic dynamics that fuel their metabolic demands, promote resistance to cytotoxic therapies, and facilitate immune evasion. This review examines the roles of endocytosis in apoptotic resistance and immune escape mechanisms utilized by cancer cells. We highlight how inhibiting endocytosis can sensitize malignant cells to therapeutic agents and restore susceptibility to PCD. Strategies to modulate endocytosis for enhanced cancer treatment are discussed, including targeting endocytic regulatory proteins, altering membrane biophysical properties, and inhibiting Rho-associated kinases. While promising, challenges remain regarding the specificity and selectivity of endocytosis-targeting agents. Nonetheless, harnessing endocytic pathways represents an attractive approach to overcome apoptotic resistance and could yield more effective therapies by rendering cancer cells vulnerable to PCD. Understanding the interplay between endocytosis and PCD regulation is crucial for developing novel anticancer strategies that selectively induce tumor cell death.

Evaluation of 3, 3’-Disubstituted Oxindoles Derivatives as a Potential Anti- Cancer Tyrosine Kinase Inhibitors-molecular Docking and ADME Studies

Aim: This study aims to explore the binding interactions between synthesized 3,3’-Disubstituted Oxindoles and the HCK enzyme, with the specific goal of discovering potential anticancer agents. Background: Cancer presents an ongoing global health challenge, necessitating the exploration of innovative therapeutic approaches. Isatin derivatives and pyridine compounds hold great promise for the development of anticancer drugs due to their wide-ranging biological activities. Moreover, HCK plays a significant role in chemotherapy resistance and reduced drug efficacy in clinical settings, highlighting its importance in the intricate network of cancer pathophysiology. There is an urgent need for targeted interventions to regulate HCK activity and enhance cancer treatment outcomes. Methods: In our study, we ensured meticulous optimization of protein and ligand preparation to guarantee accurate docking simulations. We conducted molecular docking analyses using the state-of-the-art Glide module and assessed ADME properties using the Schrödinger suite's QikProp tool. Results: Through molecular docking, compounds 3c and 3e have emerged as promising anticancer agents with low docking scores against Tyrosine Kinase. Further ADME analysis has provided valuable insights into the compounds' in-silico behaviour, while computed dipole moments have enhanced our understanding of their physicochemical characteristics Conclusion: In this study, we explored how the synthesized compounds bind within the HCK active site, indicating potential anticancer properties. Through in silico docking, we identified compounds 3c and 3e as possible anticancer agents, with the lowest docking scores of -7.621 and -7.602 kcal/mol against Tyrosine Kinase. These findings emphasize the importance of computational approaches in drug discovery and offer valuable insights for future research and development efforts.

From Hyperinsulinemia to Cancer Progression: How Diminishing Glucose Storage Capacity Fuels Insulin Resistance

ABSTRACTBackgroundType 2 diabetes (T2D) is a complex metabolic disorder characterized by insulin resistance, hyperglycemia, and hyperinsulinemia. A significant portion of individuals with T2D are unaware of their condition until it has reached advanced stages. T2D is also associated with an increased risk and worse prognosis of cardiovascular disease, cognitive decline, and cancer. Understanding the mechanisms underlying the emergence of insulin resistance is critical for improving early detection and therapeutic interventions.MethodsAn updated framework is proposed to describe the emergence of insulin resistance that precedes the development of T2D. The model focuses on the impact of diminishing capacity to store excess glucose, which can occur due to a multitude of factors, including age‐related muscle loss. The model is used to simulate responses to oral glucose tolerance tests (OGTTs) to capture the transition from a normal to a diabetic phenotype, as defined by the Kraft criteria. Additionally, the model is used to explore how the metabolic environment influences tumor progression, drawing on experimental data regarding the impact of transient diabetic phenotypes and hyperinsulinemia on cancer therapy efficacy.ResultsThe model successfully demonstrates that reduced glucose storage capacity can qualitatively reproduce the progression from normal to diabetic phenotypes observed in OGTT responses. Furthermore, it shows that tumor progression or regression is highly dependent on the host's metabolic environment, particularly hyperinsulinemia. This aligns with experimental results that connect drug‐induced hyperinsulinemia to a loss of therapeutic efficacy against tumors, whereas the reversal of the diabetic phenotype could restore drug sensitivity and treatment response.ConclusionsThis study highlights the critical role of hyperinsulinemia, even in normoglycemic individuals, in both the progression of T2D and the modulation of cancer therapy outcomes. Addressing hyperinsulinemia emerges as a promising strategy to enhance cancer treatment efficacy and improve overall health outcomes in patients with or at risk for T2D.

Synergistic combination effect of the PCA-1/ALKBH3 inhibitor HUHS015 on prostate cancer drugs in vitro and in vivo.

Prostate cancer antigen-1/ALKBH3, a DNA/RNA demethylase of 3-methylcytosine, 1-methyladenine (1-meA), and 6-meA, was found in prostate cancer as an important prognostic factor. Additionally, 1-meA has been associated with other cancers. The ALKBH3 inhibitor HUHS015 was found to be effective against prostate cancer both in vitro and in vivo. Herein, we investigated the effect of HUHS015 in combination with drugs for prostate cancer approved in Japan (including bicalutamide, cisplatin, mitoxantrone, prednisolone, ifosfamide, tegafur/uracil, docetaxel, dacarbazine, and estramustine) by treating DU145 cells with around IC50 value concentrations of these drugs for 3 days. Additionally, the cells were observed for additional 9 days after drug removal. Combination treatment with dacarbazine, estramustine, tegafur/uracil, and HUHS015 showed a slight additive effect after 3 days. After drug washout of them and mitoxantrone, the combined effects and levels were enhanced and sustained, although the effects of each treatment alone declined. HUHS015 combined with cisplatin or docetaxel elicited synergistic and sustained effects. In vivo, combining HUHS015 and docetaxel, the first chemotherapeutic agent for castration-resistant prostate cancer, showed notable effects in the DU145 xenograft model. In conclusion, HUHS015 exhibited a synergistic effect with docetaxel and drugs acting on DNA in vitro, even after drug removal. Since cancer chemotherapy is typically administered during rest periods due to its high toxicity, combining it with an ALKBH3 inhibitor could be a promising strategy for enhancing cancer treatment, as it can elicit an additive effect during treatment, allowing dosage reduction, and synergistically sustain the effect after drug washout during rest periods.

Engineered T cells for Colorectal Cancer.

Colorectal cancer (CRC) is a major contributor to global cancer incidence and mortality. Conventional treatments have limitations; hence, innovative approaches are imperative. Recent advancements in cancer research have led to the development of personalized targeted therapies and immunotherapies. Immunotherapy, in particular, T cell-based therapies, exhibited to be promising in enhancing cancer treatment outcomes. This review focuses on the landscape of engineered T cells as a potential option for the treatment of CRC. It highlights the approaches, challenges and current advancements in this field. As the understanding of molecular mechanisms increases, engineered T cells hold great potential in revolutionizing cancer treatment. To fully explore their safety efficacy in improving patient outcomes, further research and clinical trials are necessary.

Zinc oxide nanoparticles: A comprehensive review on its synthesis, anticancer and drug delivery applications

Zinc oxide nanoparticles (ZnONPs), are becoming a more useful tool in a number of fields, including electronics, food packaging, optics, and most significantly, medicinal applications. These nanoparticles show a special capacity to target cancer cells specifically, dissolving into Zn2+ ions in an acidic environment. This leads to the generation of reactive oxygen species that specifically induce cytotoxic effects in malignant cells. Furthermore, ZnONPs work well as carriers to deliver certain anticancer medications straight into tumour cells. Growing interest in ZnONPs has prompted the creation of a variety of production methods, including chemical, physical, and environmentally benign biological approaches. This review explores the biomedical uses of ZnONPs and their production techniques, with an emphasis on the anticancer properties of the compounds. Detailed investigations into the mechanisms by which ZnONPs combat various cancers, influenced by their size, shape, and surface properties, are discussed. Additionally, their role in enhancing cancer treatment through the combined use of chemotherapy and photodynamic therapy, triggered by exposure to ultraviolet (UV) or near-infrared (NIR) light, is examined. The paper further explores the drug delivery capabilities of ZnONPs, including drug loading, stimulus-responsive controlled release, and therapeutic advantages. Finally, the future prospects of ZnONPs research and applications are considered, highlighting potential advancements and innovations

Gold nanoparticle effect on dose and DNA damage enhancement in the vicinity of gold nanoparticles

This study uses Monte Carlo simulations to examine the dose enhancement effect of gold nanoparticles (AuNPs) in radiation therapy and its effects on DNA damage. Using the GATE- 9.0 and Geant4-DNA packages, Monte Carlo simulations were used to simulate a mathematical phantom and determine the energy deposition in the vicinity of AuNP. The simulations were conducted for various photon beam energies (50, 100, 250, and 6000 keV) with and without the presence of different-size AuNPs (10, 30, 50 and 100 nm). The dose enhancement factor (DER) was evaluated using Geant4-DNA to examine the effects AuNP sizes and photon beam energies on DNA damage. A multi-scale Monte Carlo simulation was conducted to evaluate enhanced DNA damage owing to nanoparticles in the proximity of cancer cells. The Monte Carlo simulations indicated that AuNPs boost the dose delivery, resulting in enhanced energy deposition and subsequent DNA damage. The DER analysis revealed a significant increase in the dose deposition within DNA, leading to single or double-strand breaks. Geant4-DNA simulations revealed information on the dosage enhancement factor for various AuNP sizes and photon beam intensities, enabling a deeper comprehension of the underlying mechanics. The outcomes of this study emphasize the potential of AuNPs as effective radiosensitizers in radiation therapy and contribute to the growing body of research on the use of nanotechnology in enhancing cancer treatment outcomes. Further investigations and experimental validations are necessary to optimize the usage of AuNPs for improved radiation therapy.

Temporal Optimization in the Synthesis of Multifunctional Nano Agents for Enhanced MRI Contrast, Hyperthermia Therapy, and ROS Generation.

Advanced methodologies, such as hyperthermia and modulation of reactive oxygen species (ROS), exhibit considerable promise in the therapeutic landscape of cancer. These strategies offer a targeted paradigm for combating malignant cells while mitigating damage to healthy tissue. Noteworthy among these approaches is the utilization of superparamagnetic iron oxide nanoparticles, which are renowned for their ability to enhance both hyperthermia and ROS generation specifically within tumor microenvironments. The objective of this investigation is to scrutinize the relationship between the reaction duration and the characteristics of carbon-doped silica core-shell iron oxide nanoparticles (CSIONPs). Specifically, we focus on CSIONP-12, CSIONP-24, and CSIONP-36, synthesized by using varying reaction periods. Through a comprehensive analysis, we primarily evaluate the impact of these formulations on T1 and T2 magnetic resonance imaging (MRI), aiming to elucidate their mechanisms and therapeutic potential in promoting hyperthermia and ROS-mediated cancer therapy. CSIONP-24 emerges as a compelling candidate due to its dual influence on magnetic hyperthermia and ROS generation, suggesting its promise in enhancing cancer treatment outcomes. Furthermore, the findings underscore the exceptional T1-T2 MRI capabilities of this technology, underscoring its versatility and efficacy in the nuanced realm of cancer theranostic.

Enhanced Intratumoral Delivery of Immunomodulator Monophosphoryl Lipid A through Hyperbranched Polyglycerol–Coated Biodegradable Nanoparticles

Immunomodulatory agents (IMA) have significant potential to enhance cancer treatment but have demonstrated limited efficacy beyond the preclinical setting due to poor pharmacokinetics and toxicity associated with systemic administration. On the other hand, when locally delivered, IMAs require repeated administration to optimize immune stimulation. To overcome these challenges, we encapsulated the toll-like receptor (TLR)4 agonist monophosphoryl lipid A (MPLA) within hyperbranched polyglycerol (HPG)-coated biodegradable nanoparticles (NP) engineered for gradual drug release from the nanoparticle core, resulting in a more persistent stimulation of anti-tumor immune responses while minimizing systemic side effects. In a model of malignant melanoma, we demonstrate that HPG-NP encapsulation significantly improves the antitumor efficacy of MPLA by enhancing its ability to remodel the tumor microenvironment (TME). Compared to free MPLA, HPG-NP-MPLA significantly increased the natural killer cell and cytotoxic T cell mediated antitumor immune response and tuned the tumor draining lymph nodes towards a T helper (Th)1 response. Furthermore, when combined with local delivery of a chemotherapeutic agent, HPG-NP-MPLA induces the conversion of an immunosuppressive TME to immunogenic TME and significantly improves survival.

"Bridging the DNA divide": Understanding the interplay between replication- gaps and homologous recombination proteins RAD51 and BRCA1/2

A key but often neglected component of genomic instability is the emergence of single-stranded DNA (ssDNA) gaps during DNA replication in the absence of functional homologous recombination (HR) proteins, such as RAD51 and BRCA1/2. Research in prokaryotes has shed light on the dual role of RAD51's bacterial ortholog, RecA, in HR and the protection of replication forks, emphasizing its essential role in preventing the formation of ssDNA gaps, which is vital for cellular viability. This phenomenon was corroborated in eukaryotic cells deficient in HR, where the formation of ssDNA gaps within newly synthesized DNA and their subsequent processing by the MRE11 nuclease were observed. Without functional HR proteins, cells employ alternative ssDNA gap-filling mechanisms to ensure survival, though this compensatory response can compromise genomic stability. A notable example is the involvement of the translesion synthesis (TLS) polymerase POLζ, along with the repair protein POLθ, in the suppression of replicative ssDNA gaps. Persistent ssDNA gaps may result in replication fork collapse, chromosomal anomalies, and cell death, which contribute to cancer progression and resistance to therapy. Elucidating the processes that avert ssDNA gaps and safeguard replication forks is critical for enhancing cancer treatment approaches by exploiting the vulnerabilities of cancer cells in these pathways

Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies.

Antibody-drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies' targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored for various tumor indications and some already approved for clinical use, challenges such as resistance due to factors like antigen expression, ADC processing, and payload have emerged. This review aims to outline the history of ADC development, their structure, mechanism of action, recent composition advancements, target selection, completed and ongoing clinical trials, resistance mechanisms, and intervention strategies. Additionally, it will delve into the potential of ADCs with novel markers, linkers, payloads, and innovative action mechanisms to enhance cancer treatment options. The evolution of ADCs has also led to the emergence of combination therapy as a new therapeutic approach to improve drug efficacy.

Multifaceted Carbonized Metal-Organic Frameworks Synergize with Immune Checkpoint Inhibitors for Precision and Augmented Cuproptosis Cancer Therapy.

The discovery of cuproptosis, a copper-dependent mechanism of programmed cell death, has provided a way for cancer treatment. However, cuproptosis has inherent limitations, including potential cellular harm, the lack of targeting, and insufficient efficacy as a standalone treatment. Therefore, exogenously controlled combination treatments have emerged as key strategies for cuproptosis-based oncotherapy. In this study, a Cu2-xSe@cMOF nanoplatform was constructed for combined sonodynamic/cuproptosis/gas therapy. This platform enabled precise cancer cotreatment, with external control allowing the selective induction of cuproptosis in cancer cells. This approach effectively prevented cancer metastasis and recurrence. Furthermore, Cu2-xSe@cMOF was combined with the antiprogrammed cell death protein ligand-1 antibody (aPD-L1), and this combination maximized the advantages of cuproptosis and immune checkpoint therapy. Additionally, under ultrasound irradiation, the H2Se gas generated from Cu2-xSe@cMOF induced cytotoxicity in cancer cells. Further, it generated reactive oxygen species, which hindered cell survival and proliferation. This study reports an externally controlled system for cuproptosis induction that combines a carbonized metal-organic framework with aPD-L1 to enhance cancer treatment. This precision and reinforced cuproptosis cancer therapy platform could be valuable as an effective therapeutic agent to reduce cancer mortality and morbidity in the future.

Ultrasound and x-ray imageable poloxamer-based hydrogel for loco-regional therapy delivery in the liver.

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

Hybrid Nanoparticles for Cancer Theranostics: A Critical Review on Design, Synthesis, and Multifunctional Capabilities.

Theranostics, a method that combines targeted therapy and diagnostic imaging, has emerged as a viable route for enhancing cancer treatment, and hybrid nanoparticles (HNPs) are at the forefront of this field. Metallic, polymeric, lipid-based, and silica- based HNPs are studied for targeting and biocompatibility. Using HNPs, chemotherapeutic drugs, small interfering RNA, and therapeutic genes can be given precisely and controlled. This enhances therapeutic efficacy and reduces adverse effects. With fluorescence dyes, MRI contrast agents, and PET tracers, real-time therapy response monitoring is conceivable. A nano platform with therapeutic and diagnostic capabilities holds great promise for personalized medicine and precision oncology. The present study discusses HNPs' biocompatibility, stability, immunogenicity, and long-term biosafety, which are crucial to the clinical translation of cancer theranostics. Further, in this in- -depth investigation, we investigated the design, synthesis, and multifunctional activities of HNPs for use in cancer theranostics.

Anti-Quenching NIR-II Excitation Phenylboronic Acid Modified Conjugated Polyelectrolyte for Intracellular Peroxynitrite-Enhanced Chemo-Photothermal Therapy.

Multidrug resistance to clinical chemotherapeutic drugs severely limits antitumor efficacy and patient survival. The integration of chemotherapy with photothermal therapy (PTT) and reactive nitrogen species has become a major strategy to enhance cancer treatment efficacy. Herein, a multifunctional peroxynitrite (ONOO-) nanogenerator (PBT/NO/Pt) for NIR-II fluorescence (NIR-II FL)/NIR-II photoacoustic (NIR-II PA) imaging-guided chemo/NIR-II PTT/ONOO- combination therapy is reported. The multifunction nanogenerator is developed by co-loading a pH-sensitive nitric oxide donor (DETA NONOate) and nicotinamide adenine dinucleotide phosphate oxidases trigger superoxide (O2 •-) generator chemotherapy drug (CDDP) to an NIR-II excitation-conjugated polyelectrolyte (PNC11BA). PNC11BA has non-conjugated alkyl chain segments in the polymer backbone and abundant positively charged phenylboronic acid in its side chains, which support the anti-quenching of NIR-II FL and the integration of DETA NONOate and CDDP into PBT/NO/Pt. In the acidic tumor microenvironment, the coordination bonds between CDDP and PNC11BA are cleaved, releasing CDDP for chemotherapeutic activity. The simultaneous release of nitric oxide (NO) and O2 •- rapidly leads to the in situ generation of the more cytotoxic reactive physiological nitrogen species ONOO-. In vitro and in vivo results prove that PBT/NO/Pt exhibited a markedly ONOO- enhanced chemo-photothermal synergistic therapy for SKOV3/DDP tumor by downregulating the intracellular glutathione and increasing CDDP-DNA adducts.

An emerging antibacterial nanovaccine for enhanced chemotherapy by selectively eliminating tumor-colonizing bacteria

Fusobacterium nucleatum (F. nucleatum), an oral anaerobe, is prevalent in colorectal cancer and is closely related to increased cancer cell growth, metastasis, and poor treatment outcomes. Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F. nucleatum, thereby enhancing cancer treatment. Although adjuvants have been employed to enhance the immune response, the vaccine’s effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular pathogens. In this study, we developed a minimalistic, biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived F. nucleatum membranes. Compared to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant, the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells, maximizing their ability to achieve effective antigen presentation and strong downstream immune progress. Notably, the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects, eliminating F. nucleatum without affecting intratumoral and gut microbiota. It significantly enhances chemotherapy efficacy and reduces cancer metastasis in F. nucleatum-infected colorectal cancer. Overall, this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer.

Metal–Organic Framework-Capped Gold Nanorod Hybrids for Combinatorial Cancer Therapy

Recently, nanomaterials have attracted extensive attention in cancer-targeting therapy and as drug delivery vehicles owing to their unique surface and size properties. Multifunctional combinations of nanomaterials have become a research hotspot as researchers aim to provide a full understanding of their nanomaterial characteristics. In this study, metal–organic framework-capped gold nanorod hybrids were synthesized. Our research explored their ability to kill tumor cells by locally increasing the temperature via photothermal conclusion. The specific peroxidase-like activity endows the hybrids with the ability to disrupt the oxidative balance in vitro. Simultaneously, chemotherapeutic drugs are administered and delivered by loading and transportation for effective combinatorial cancer treatment, thereby enhancing the curative effect and reducing the unpredictable toxicity and side effects of large doses of chemotherapeutic drugs. These studies can improve combinatorial cancer therapy and enhance cancer treatment.

Control of acute myeloid leukemia and generation of immune memory in vivo using AMV564, a bivalent bispecific CD33 x CD3 T cell engager.

Off-the-shelf immunotherapeutics that suppress tumor growth and provide durable protection against relapse could enhance cancer treatment. We report preclinical studies on a CD33 x CD3 bivalent bispecific diabody, AMV564, that not only suppresses tumor growth, but also facilitates memory responses in a mouse model of acute myelogenous leukemia (AML). Mechanistically, a single 5-day treatment with AMV564 seems to reduce tumor burden by redirection of T cells, providing a time window for allogeneic or other T cells that innately recognize tumor antigens to become activated and proliferate. When the concentration of bispecific becomes negligible, the effector: target ratio has also shifted, and these activated T cells mediate long-term tumor control. To test the efficacy of AMV564 in vivo, we generated a CD33+ MOLM13CG bioluminescent human cell line and optimized conditions needed to control these cells for 62 days in vivo in NSG mice. Of note, not only did MOLM13CG become undetectable by bioluminescence imaging in response to infusion of human T cells plus AMV564, but also NSG mice that had cleared the tumor also resisted rechallenge with MOLM13CG in spite of no additional AMV564 treatment. In these mice, we identified effector and effector memory human CD4+ and CD8+ T cells in the peripheral blood immediately prior to rechallenge that expanded significantly during the subsequent 18 days. In addition to the anti-tumor effects of AMV564 on the clearance of MOLM13CG cells in vivo, similar effects were seen when primary CD33+ human AML cells were engrafted in NSG mice even when the human T cells made up only 2% of the peripheral blood cells and AML cells made up 98%. These studies suggest that AMV564 is a novel and effective bispecific diabody for the targeting of CD33+ AML that may provide long-term survival advantages in the clinic.

Impact of Combination Therapy with Chemical Drugs and Megavoltage X-ray Exposure on Breast Cancer Stem Cells' Viability and Proliferation of MCF-7 and MDA-MB-231 Cell Lines.

Breast Cancer (BC) is a serious malignancy among women. However, chemotherapy is an important tool for cancer treatments, but the long-term use of chemotherapy drugs may lead to drug resistance and tumor recurrence. Since Breast Cancer Stem Cells (BCSCs) can be the main factor to induce BC treatment resistance and recurrence, investigation of BCSCs signaling pathways can be an effective modality to enhance cancer treatment efficiency. In this study, the effect of metformin, SB203580, and takinib alone or in combination with radiotherapy on MCF-7 and MDA-MB-231 breast cancer cell lines was evaluated. MCF-7 and MDA-MB-231 breast cancer cell lines were treated with metformin, SB203580, and takinib for 24 or 48 hours, followed by X-ray exposure. The MTT assay and flow cytometry analysis were performed to assess cell growth inhibition and cellular death, CXCr4 expression, and BCSCs, respectively. The results showed the combination of takinib/SB203580 with radiotherapy to remarkably reduce the CXCR4 expression and BCSCs levels in the MCF-7 cell line. Also, the concurrent administration of takinib/metformin/radiotherapy significantly reduced BCSCs and CXCR4 metastatic markers in the MDA-MB- 231 cells. Since the MAPK signaling pathway has an important role in inducing drug resistance and cell proliferation, the use of SB203580 as an inhibitor of p38 MAPK can improve breast cancer treatment. Furthermore, metformin and ionizing radiation by suppression of the mTOR signaling pathway can control AMPK activation and cellular proliferation. Anti-cancer and cytotoxic effects of metformin can be effective in this strategy. In conclusion, the combination of conventional chemotherapeutic drugs, including SB203580, metformin, and takinib with X-ray exposure can be a new approach to diminish the drug resistance of breast cancer.

Deciphering the Prognostic Efficacy of MRI Radiomics in Nasopharyngeal Carcinoma: A Comprehensive Meta-Analysis.

This meta-analysis investigates the prognostic value of MRI-based radiomics in nasopharyngeal carcinoma treatment outcomes, specifically focusing on overall survival (OS) variability. The study protocol was registered with INPLASY (INPLASY202420101). Initially, a systematic review identified 15 relevant studies involving 6243 patients through a comprehensive search across PubMed, Embase, and Web of Science, adhering to PRISMA guidelines. The methodological quality was assessed using the Quality in Prognosis Studies (QUIPS) tool and the Radiomics Quality Score (RQS), highlighting a low risk of bias in most domains. Our analysis revealed a significant average concordance index (c-index) of 72% across studies, indicating the potential of radiomics in clinical prognostication. However, moderate heterogeneity was observed, particularly in OS predictions. Subgroup analyses and meta-regression identified validation methods and radiomics software as significant heterogeneity moderators. Notably, the number of features in the prognosis model correlated positively with its performance. These findings suggest radiomics' promising role in enhancing cancer treatment strategies, though the observed heterogeneity and potential biases call for cautious interpretation and standardization in future research.