Treatment Of Cancer Research Articles

Dendritic Cell Plasticity, Radiation, and Newton's Third Law.

Regulatory T (Treg) cells protect damaged tissues but can undermine the effects of cancer treatments, including radiation (RTx). Intratumoral immuno-stimulatory dendritic cells (cDC1) respond to RTx with production of Treg-attracting MDC/CCL22, undermining RT effects. That effect can be reversed by EGFR-targeted IFNa, highlighting cDC1 plasticity and relevance as therapeutic targets.

Monoclonal Antibodies and Antibody-drug Conjugates as Emerging Therapeutics for Breast Cancer Treatment.

When breast cells divide and multiply out of control, it is called breast cancer. Symptoms include lump formation in the breast, a change in the texture or color of the breast, or a discharge from the nipple. Local or systemic therapy is frequently used to treat breast cancer. Surgical and radiation procedures limited to the affected area are examples of local management. There has been significant worldwide progress in the development of monoclonal antibodies (mAbs) since 1986, when the first therapeutic mAb, Orthoclone OKT3, became commercially available. mAbs can resist the expansion of cancer cells by inducing the destruction of cellular membranes, blocking immune system inhibitors, and preventing the formation of new blood vessels. mAbs can also target growth factor receptors. Understanding the molecular pathways involved in tumor growth and its microenvironment is crucial for developing effective targeted cancer therapeutics. Due to their unique properties, mAbs have a wide range of clinical applications. Antibody-drug conjugates (ADCs) are drugs that improve the therapeutic index by combining an antigen-specific antibody with a payload. This review focuses on the therapeutic applications, mechanistic insights, characteristics, safety aspects, and adverse events of mAbs like trastuzumab, bevacizumab, pertuzumab, ertumaxomab, and atezolizumab in breast cancer treatment. The creation of novel technologies utilizing modified antibodies, such as fragments, conjugates, and multi-specific antibodies, must be a central focus of future studies. This review will help scientists working on developing mAbs to treat cancers more effectively.

Molecular Docking of Phytomolecules of Grain Amaranth (Amaranthus hypochondriacus) with AKR1C3Protein Involved in Prostate Cancer in Human Beings

Abstract: This study focuses on exploring how the bioactive compounds found in amaranth— phytol, squalene, and α-tocopherol—could potentially offer medicinal benefits in the context of prostate cancer. The investigation involves a docking study with AKRC13, an important target linked to the control of prostate cancer, aiming to uncover their potential effects against this disease. Costeffective and efficient cancer treatment options are crucial because of the high expenses associated with current cancer therapies as well as their side effects. Amaranth (Amaranthus hypochondriacus) is a pseudocereal crop abundant in squalene, α-tocopherol, and phytol, which shows promising foodbased therapy for various diseases, including cancer. Prostate cancer has been a significant contributor to mortality globally, but the introduction of relugolix has emerged as a crucial therapeutic intervention in its treatment. Hence, this study was conducted to investigate the interactions between grain amaranth bioactive compounds squalene, phytol, and α-tocopherol with AKRC13 protein utilizing a molecular docking approach facilitated by Autodock Vina software. Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB-PDB) (http://www.rcsb.org/) was used for retrieving the 3D crystal structure of the target protein, AKRC13 (PDB ID: 7c7f). The 3D structure of bioactive compounds squalene, phytol, and α-tocopherol were retrieved from the PubChem database, following which Open-Babel was used to change the format from .sdf to .pdb. Furthermore, pharmacokinetics characteristics were also considered along with Lipinski’s rule of five using SwissADME (http://www. Swiss adme.ch/index.php) and pkCSM (http://structure.bioc.cam.ac.uk/pkcsm), indicating their potential as a drug candidate in the initial stage. The potential anticancer properties of the ligands were predicted using PASS software. Following the completion of the docking study, it became evident that α-tocopherol demonstrated the most significant binding energy, followed by squalene and phytol, in comparison to the established drug, relugolix. This implies that the chosen bioactive compounds might possess enzyme-inhibiting properties, indicating their potential for further in vivo anticancer screening using model organisms. The findings serve as stepping stones for advancing the potential use of the discussed bioactive compounds as a potential drug candidate for prostate cancer.

Mild heat shock at 40°C increases levels of autophagy: Role of Nrf2.

The exposure to low doses of stress induces an adaptive survival response that involves the upregulation of cellular defense systems such as heat shock proteins (Hsps), anti-apoptosis proteins, and antioxidants. Exposure of cells to elevated, non-lethal temperatures (39-41°C) is an adaptive survival response known as thermotolerance, which protects cells against subsequent lethal stress such as heat shock (>41.5°C). However, the initiating factors in this adaptive survival response are not understood. This study aims to determine whether autophagy can be activated by heat shock at 40°Cand if this response is mediated by the transcription factor Nrf2. Thermotolerant cells, which were developed during 3h at 40°C, were resistant to caspase activation at 42°C. Autophagy was activated when cells were heated from 5 to 60min at 40°C. Levels of acidic vesicular organelles (AVOs) and autophagy proteins Beclin-1, LC3-II/LC3-I, Atg7, Atg5, Atg12-Atg5, and p62 were increased. When Nrf2 was overexpressed or depleted in cells, levels of AVOs and autophagy proteins were higher in unstressed cells, compared to the wild type. Stress induced by mild heat shock at 40°C further increased levels of most autophagy proteins in cells with overexpression or depletion of Nrf2. Colocalization of p62 and Keap1 occurred. When Nrf2 levels are low, activation of autophagy would likely compensate as a defense mechanism to protect cells against stress. An improved understanding of autophagy in the context of cellular responses to physiological heat shock could be useful for cancer treatment by hyperthermia and the protective role of adaptive responses against environmental stresses.

Green Synthesis, Chemical Characterization, Antioxidant, Cytotoxicity and Anticancer Effects of Vanadium Nanoparticles

Silybum marianum is a plant with many remedial properties and may help prevent the cancer spread. Studies in this field show that this plant can reduce the growth of cancer cells. Probably, Silybum marianum will improve the effectiveness of chemotherapy. Also, the side effects of the recent treatments may be reduced by using this plant. The Food and Drug Administration has not confirmed Silybum marianum for the cancer treatment, but it may be effective in the treatment of these cancers: prostate, breast, cervical, blood, small intestine, and skin. Researching formulation of metallic nanoparticles by medicinal plants is the research priority of all countries. In the current experiment, we synthesize the vanadium nanoparticles by the watery extract of the Silybum marianum aerial parts. The characterization was conducted by field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction analysis, fourier transform infrared, energy-dispersive X-ray spectroscopy, and ultraviolet–visible spectroscopy. The DPPH inhibition efficacy was assessed by the DPPH examination, while the MTT assay was used to evaluate anti-cervical cancer (against LM-MEL-41, HT-3, Ca Ski, DoTc2 4510, SiHa, and C-33 A cells) and cytotoxicity efficacy of vanadium NPs. In XRD, the signals at 2 theta values of 25.13, 27.77, 44.94, 49.52, 66.28, and 70.57 belong to the planes of (202), (103), (401), (205), (406), and (125) respectively. Based on the findings of FE-SEM, the NPs are formed with the morphology of spherical with an aggregation. In FT-IR, the peaks at 416 and 551 cm−1 can be assigned to V–O–V and V–O bonds. The EDS analysis confirms the vanadium presence by the signals at 5.45 (VKβ), 4.98 (VKα), and 0.53 (VLα). The other signals below 0.5 KeV verify the appearance of carbon and oxygen in the green synthetic vanadium nanoparticles. The V nanoparticles IC50 was 126, 157, 165, 125, 132, and 197 μg/mL against LM-MEL-41, HT-3, DoTc2 4510, C-33 A, SiHa, and Ca Ski cervical cancer cells, respectively.

V. Craig Jordan obituary: pharmacologist who revolutionized breast cancer treatments.

V. Craig Jordan obituary: pharmacologist who revolutionized breast cancer treatments.

Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.

Chemotherapy is still the major method of treatment for many types of cancer. Curative cancer therapy is hampered significantly by medication resistance. Acidic organelles like lysosomes serve as protagonists in cellular digestion. Lysosomes, however, are gaining popularity due to their speeding involvement in cancer progression and resistance. For instance, weak chemotherapeutic drugs of basic nature permeate through the lysosomal membrane and are retained in lysosomes in their cationic state, while extracellular release of lysosomal enzymes induces cancer, cytosolic escape of lysosomal hydrolases causes apoptosis, and so on. Drug availability at the sites of action is decreased due to lysosomal drug sequestration, which also enhances cancer resistance. This review looks at lysosomal drug sequestration mechanisms and how they affect cancer treatment resistance. Using lysosomes as subcellular targets to combat drug resistance and reverse drug sequestration is another method for overcoming drug resistance that is covered in this article. The present review has identified lysosomal drug sequestration as one of the reasons behind chemoresistance. The article delves deeper into specific aspects of lysosomal sequestration, providing nuanced insights, critical evaluations, or novel interpretations of different approaches that target lysosomes to defect cancer.

Dietary Plant Metabolites Induced Epigenetic Modification as a Novel Strategy for the Management of Prostate Cancer.

Prostate cancer is a widespread malignancy among men, with a substantial global impact on morbidity and mortality. Despite advances in conventional therapies, the need for innovative and less toxic treatments remains a priority. Emerging evidence suggests that dietary plant metabolites possess epigenetic-modifying properties, making them attractive candidates for prostate cancer treatment. The present work reviews the epigenetic effects of dietary plant metabolites in the context of prostate cancer therapy. We first outline the key epigenetic mechanisms involved in prostate cancer pathogenesis, including histone modifications, DNA methylation, and miRNA or Long Noncoding RNA (lncRNA) dysregulation. Next, we delve into the vast array of dietary plant metabolites that have demonstrated promising anti-cancer effects through epigenetic regulation. Resveratrol, minerals, isothiocyanates, curcumin, tea polyphenols, soy isoflavones and phytoestrogens, garlic compounds, anthocyanins, lycopene, and indoles are among the most extensively studied compounds. These plant-derived bioactive compounds have been shown to influence DNA methylation patterns, histone modifications, and microRNA expression, thereby altering the gene expression allied with prostate cancer progression, cell proliferation, and apoptosis. We also explore preclinical and clinical studies investigating the efficacy of dietary plant metabolites as standalone treatments or in combination with traditional treatments for people with prostate cancer. The present work highlights the potential of dietary plant metabolites as epigenetic modulators to treat prostate cancer. Continued research in this field may pave the way for personalized and precision medicine approaches, moving us closer to the goal of improved prostate cancer management.

A Study Against Colon Cancer Mechanism of Xanthium sibiricum Herba Based on Computer Simulation and Bioinformatics.

Cancer is one of the leading causes of death worldwide, accounting for nearly one in six deaths in 2020. As a folk medicine, Xanthium sibiricum Herba (XSH) has been used many times in clinical practice for the treatment of various diseases. With the increasing number of cancer patients, there is a clinical need to find effective anti-cancer drugs. This study aims to explores the bioactivity and the anti-cancer mechanism of XSH. In this study, bioinformatics, network pharmacology, molecular docking, molecular dynamics simulation techniques, and apoptosis assay were used to explore the bioactivity and the anti- cancer mechanism of XSH. Finally, seven active ingredients in XSH after the screening were obtained, the two most active compounds were β-sitosterol and aloe-emodin, and good anti-cancer activity of XSH was predicted. Four core targets were obtained from the PPI network map, namely Caspase-3 (CASP3), Transcription factor AP-1 (JUN), Myc proto-oncogene protein (MYC), and cellular tumor antigen p53 (TP53). GO and KEGG analyses showed that the mechanism of XSH anti-cancer is mainly related to the apoptosis process, and the main signaling pathways are enriched in the p53 signaling pathway, Apoptosis, and MAPK signaling. The molecular docking and molecular dynamics simulation results showed that CASP3, JUN, MYC, and TP53 had a high affinity with β- sitosterol and aloe-emodin. Bioinformatics analyses demonstrated the importance of core targets. Apoptosis assay showed that XSH could significantly promote the apoptosis of cancer cells, and inhibit their proliferation and migration, especially colon cancer cells. This study uncovered the main active components, bioactivities, and potential targets of XSH, and further revealed the multi-component, multi-target, and multi-pathway mechanism of XSH for cancer treatment and promoting apoptosis.

Co-Delivery of Tim-3 Monoclonal Antibody and Sorafenib to Enhance Chemoimmunotherapy of Liver Cancer by Using Silicon Nanosystem

In this study, mesoporous silica nanosystem (ST/SNs) was designed to co-deliver Tim-3 mAb and sorafenib (SF) for combined chemoimmunotherapy of liver cancer. The outer shell of ST/SNs is composed of Tim-3 mAb modified with metalloproteinase 2 (MMP2)-sensitive peptide, which acts as a “gating molecule” in the blood circulation to prevent drug release, and responds to Tim-3 mAb under the action of MMP2 in the tumor microenvironment Shedding enables Tim-3 mAb and SF-triggered drug release for heterotargeted cell delivery to T cells/tumor cells. In vivo tumor inhibition experiments showed that ST/SNs significantly improved tumor inhibition in tumor-bearing mice compared with sequential administration of free SF and Tim-3 mAb. At the same time, ST/SNs significantly up-regulated the expression of anti-tumor cytokines IFN-γ and IL-12 in mouse serum and the proportion of CD3+CD4+ and CD3+CD8+ cells in the tumor, showing a good immune regulation ability. In addition, at the administered dose, the blank vector exhibited low cytotoxicity and hemolysis, and no obvious hemolysis was observed. Provincial People’s Hospital. In conclusion, this study provides a promising chemoimmunotherapy combination drug combination for clinical liver cancer treatment, and provides a potential drug carrier for chemoimmunotherapy combination therapy.

Cytokine release syndrome after CAR T-cell therapy for B-cell acute lymphoblastic leukemia in children and young adolescents: storms make trees take deeper roots.

Chimeric antigen receptor (CAR) T-cells have revolutionized cancer treatment, showing significant success, including treatment of pediatric B-cell acute lymphoblastic (B-ALL) leukemia. Despite their efficacy, Cytokine release syndrome (CRS) emerges as a common early adverse effect that can be life threatening in severe cases, resulting from the immune system's targeted activation against tumors. This review concentrates on CRS in children and young adults undergoing CAR T-cell therapy for B-ALL. It explores CRS pathophysiology, clinical presentation, and incidence, emphasizing the importance of a consensus definition and grading to homogenize the treatment according to the severity of symptoms. We will discuss the standard of care treatment of CRS but also novel approaches. We will highlight the importance of managing CRS without compromising the efficacy of immune cell activation against tumors. As CAR T-cell therapy in pediatric B-ALL become increasingly available and used, optimal management of cytokine release syndrome becomes increasingly important. Early recognition and timely management has improved. Further information will aid us to identify optimal timing of tocilizumab and corticosteroids. Continued bench research coupled with clinical studies and biomarker discovery will allow for valuable insights into CRS pathophysiology and patient-and/or cell-targeted treatments.

Resveratrol: Targeting Cancer Stem Cells and ncRNAs to Overcome Cancer Drug Resistance.

A major challenge in treating cancer is the development of drug resistance, which can result in treatment failure and tumor recurrence. Targeting cancer stem cells (CSCs) and non-coding RNAs (ncRNAs) with a polyphenolic substance called resveratrol has the ability to combat this problem by lowering cancer resistance to drugs and opening up new therapeutic options. Resveratrol alters the expression of genes related to self-renewal, modulating important signaling pathways involved in cancer initiation and CSC control. Additionally, resveratrol affects non-coding RNAs (ncRNAs), including Micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs which are essential for stemness, drug resistance, and other cancer-related activities. Numerous studies have shown that resveratrol has the potential to be an effective anticancer drug when used in combination therapy, but issues with absorption and pharmacokinetics still need to be resolved before it can be used in clinical applications. Reducing chemotherapy resistance by better understanding the intricate mechanisms by which resveratrol affects cancer cells and CSCs, as well as its impact on ncRNA expression, could eventually contribute to more effective cancer treatments. To completely understand these pathways and optimize the utilization of resveratrol in combination treatments, additional study is necessary.

Identification of an Exosome-relevant SNHG6-hsa-miR-429- CHRDL1/CCNA2 Axis for Lung Adenocarcinoma Prognosis Evaluation.

To explore an exosome-relevant molecular classification in lung adenocarcinoma (LUAD). Exosome genes or relevant non-coding RNAs are regulators of cancer treatment and prognosis, but their function in LUAD has not yet been determined. Unraveling a molecular classification applying exosome-related RNA networks for LUAD prognosis evaluation. MicroRNA sequencing data (miRNAs-seq) and RNA sequencing data (RNA- seq) were derived from The Cancer Genome Atlas (TCGA). The ConsensusCluster- Plus package was used for molecular typing in LUAD based on 121 Exosome-related genes. Then, a limma package was conducted to explore differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in molecular typing for constructing an Exosome-driven competing endogenous RNA network (ceRNA). Dominant miRNAs, as well as target mRNAs, were identified by COX modeling and Kaplan-Meier survival analysis. Two Exosome-associated molecular clusters classified in LUAD. The C2 cluster favored high clinicopathology and showed a trend toward poor prognosis. 29 lncRNA- miRNA and 12 miRNA-mRNA interaction pairs were identified. The hsa-miR-429 was the pivotal miRNA in the network that affected the prognosis of LUAD. According to the interaction relationship and LUAD prognostic role, SNHG6-hsa- miR-429-CHRDL1/CCNA2 was identified. SNHG6-hsa-miR-429-CHRDL1 exerts oncogenic effects, and SNHG6-hsa-miR-429- CCNA2 exerts pro-oncogenic effects. Overall, our study identified an Exosome-driven ceRNA network in LUAD, and the SNHG6-hsa-miR-429-CHRDL1/CCNA2 axis could be a new therapeutic target for LUAD and our study provides new insights into the molecular mechanisms of LUAD.

Synthesis and in-silico Studies of 4-phenyl thiazol-2-amine Derivatives as Putative Anti-breast Cancer Agents.

Breast cancer (BC) is the second-leading cause of cancer-related fatalities in women after lung cancer worldwide. The development of BC is significantly influenced by estrogen receptors (ERs). The problem with current cancer treatments is selectivity, target specificity, cytotoxicity, and developing resistance. Thiazole scaffolds are gaining popularity in drug discovery due to their broad range of biological activity. It has the extraordinary capacity to control a variety of cellular pathways, and its potential for selective anticancer activity can be explored. Synthesis and in-silico</i> studies of 4-Phenyl thiazol-2-amine derivatives as anti-breast cancer agents and molecular docking was used to assess the compounds' capacity to bind ER-α protein target. In this study, 4-Phenylthiazol-2-amine derivatives (3a-j) have been synthesized, and using Schrodinger software, molecular docking and ADME studies of the compounds were conducted. Most of the synthesized compounds have shown dock scores ranging from -6.658 to - 8.911 kcal/mol, which is better than the standard drug tamoxifen (-6.821 kcal/mol). According to molecular docking, all compounds fit in the protein's active site and have the same hydrophobic pocket as the standard drug tamoxifen. Further, all of the compounds' ADME properties are below acceptable limits. Compound 3e showed the best docking score of -8.911. All compounds' ADME properties are within acceptable limits, and their p/o coefficients fall within a range, suggesting they will all have sufficient absorption at the site of action. These compounds can be evaluated invitro</i> and in-vivo</i> in the future.

Racial-Ethnic Comparison of Treatment for Papillary Thyroid Cancer in the Military Health System.

We aimed to compare Asian or Pacific Islander, Black, Hispanic, and non-Hispanic White patients in treatment for papillary thyroid cancer (PTC) in the equal access Military Health System to better understand racial-ethnic cancer health disparities observed in the United States. We used the MilCanEpi database to identify a cohort of men and women aged 18 or older who were diagnosed with PTC between 1998 and 2014. Low- or high-risk status was assigned using tumor size and lymph node involvement. Treatment with surgery (e.g., thyroidectomy) overall and treatment by risk status [active surveillance (low-risk) or adjuvant radioactive iodine (RAI) (high-risk)] was compared between racial-ethnic groups using multivariable logistic regression and expressed as adjusted odds ratios (AOR) with 95% confidence intervals (CIs). The study included 598 Asian, 553 Black, 340 Hispanic, and 2958 non-Hispanic White patients with PTC. Asian (AOR = 1.21, 95% CI 0.98, 1.49), Black (AOR = 1.07, 95% CI 0.87, 1.32), and Hispanic (AOR = 0.92, 95% CI 0.71, 1.19) patients were as likely as White patients to receive surgery. By risk status, there were no significant racial-ethnic differences in receipt of active surveillance or thyroidectomy for low-risk PTC or in thyroidectomy or total thyroidectomy with adjuvant RAI for high-risk PTC. In the Military Health System, where patients have equal access to care, there were no overall racial-ethnic differences in surgical treatment for PTC. As American Thyroid Association guidelines evolve to include more conservative treatment, further research is warranted to understand potential disparities in active surveillance and surgical management in U.S. healthcare settings.

Alpha T-catenin: a crucial tumor suppressor in cancer pathogenesis.

Alpha T-catenin has recently been identified as a crucial tumor suppressor in various cancer types, with roles that go beyond just providing structural support in adherens junctions. This review brings together recent findings on alpha T-catenin's important involvement in key signaling pathways related to cancer progression. We present strong evidence of its regulatory role in Wnt signaling, a pathway often disrupted in colorectal cancer, and explain how it inhibits cell proliferation and tumor growth. We also discuss the significant downregulation of alpha T-catenin in colorectal cancers and its potential as a prognostic marker. Moreover, this review looks at how increasing alpha T-catenin levels can reduce tumor growth and spread, suggesting new therapeutic strategies. Additionally, we reveal alpha T-catenin's unexpected impact on NF-κB signaling in basal E-cadherin-negative breast cancer, expanding its importance across different cancer types. By bringing these findings together, we provide a thorough understanding of alpha T-catenin's tumor-suppressing actions, setting the stage for new targeted therapies and diagnostic tools in cancer treatment.

Modifiable risk factors for weight loss after cancer treatment in Korean gastric cancer survivors.

Weight loss is a critical problem in gastric cancer survivor (GCS) associated with worse prognosis and quality of life. Nevertheless, modifiable factors related to weight loss of GCS seem limited. We investigated the factors with significant weight loss including dietary pattern change in GCS. In this cross-sectional study, Korean cancer survivors were recruited from two university-affiliated hospitals from 2014 to 2017. Overall, 591 GCSs were analyzed by preoperative body mass index levels. Significant and severe weight loss was defined as a weight reduction of more than 5% and 10%, respectively. Around 68.7% and 35.0% of GCS reported significant and severe weight loss, respectively. Age and surgery type were the important factors related to significant weight loss in total. In preoperative overweight or obese subjects, sex and surgery type were the risk factors for weight loss. Total food intake reduction was the only modifiable factor of significant weight loss (adjusted odds ratio (aOR) 1.78, 95% confidence interval (CI) 1.19-2.64), particularly in preoperative normal or underweight GCS (aOR 2.62, 95% CI 1.44-4.78). Increasing vegetable and salt reduction was found to be related to a lower risk of significant weight loss. The impact of reducing processed meat on weight loss differed by degree of weight loss and preoperative BMI level. Changing food consumption was the important modifiable factor related to significant weight loss which was more evident in preoperative underweight or normal GCS. Thus, further specific dietary recommendation is necessary for them to prevent significant weight loss. In order to prevent significant weight loss, dietary modification should be provided to GCS to ensure that total foodintake does not decrease.

Biomineralization-Tuned Nanounits Reprogram the Signal Transducer and Activator of Transcription 3 Signaling for Ferroptosis-Immunotherapy in Cancer Stem Cells.

Cancer stem cells (CSCs) are promising targets for improving anticancer treatment outcomes while eliminating recurrence, but their treatment remains a major challenge. Here, we report a nanointegrative strategy to realize CSC-targeted ferroptosis-immunotherapy through spatiotemporally controlled reprogramming of STAT3-regulated signaling circuits. Specifically, STAT3 inhibitor niclosamide (Ni) and an experimental ferroptosis drug (1S, 3R)-RSL3 (RSL3) are integrated into hyaluronic acid-modified amorphous calcium phosphate (ACP) nanounits through biomineralization (CaP-PEG-HA@Ni/RSL3), which could be recognized by CD44-overexpressing CSCs and released in a synchronized manner. Ni inhibits the CSC-intrinsic STAT3-PD-L1 axis to stimulate adaptive immunity and enhance interferon gamma (IFNγ) secretion by CD8+ T cells to downregulate SLC7A11 and SLC3A2 for blocking glutathione biosynthesis. Meanwhile, Ni-dependent STAT3 inhibition also upregulates ACSL4 through downstream signaling and IFNγ feedback. These effects cooperate with RSL3-mediated GPX4 deactivation to induce pronounced ferroptosis. Furthermore, CaP-PEG-HA@Ni/RSL3 also impairs the immunosuppressive M2-like tumor-associated macrophages, while Ca2+ ions released from degraded ACP could chelate with lipid peroxides in ferroptotic CSCs to avoid CD8+ T-cell inhibition, thus boosting the effector function of activated CD8+ T cells. This study offers a cooperative ferroptosis-immunotherapeutic approach for the treatment of refractory cancer.

A tumor targeted nano micelle carrying astragaloside IV for combination treatment of bladder cancer

Immune checkpoint inhibitors (ICIs) are effective agents for tumor immunotherapy. However, their clinical effectiveness is unsatisfactory due to off-target effects and a suppressive immune microenvironment. This study developed a nanodrug delivery system for bladder cancer (BCa) using PCL-MPEG and PCL-PEG-CHO to synthesize internal hydrophobic and external hydrophilic micelles (PP) that encapsulated water-insoluble astragaloside IV (PPA). The aldehyde group on the surface of PPA reacted with the amino group of aPD-L1, allowing the decoration of this antibody on the surface of the micelles. The resultingPPA@aPD-L1effectively piggybacked astragaloside IV and aPD-L1 antibody. These findings suggest that PPA@aPD-L1 is relatively stable in circulation and efficiently binds to BCa cells with the aid of aPD-L1. Additionally, this strategy prolongs the drug’s retention time in tumors. Compared to PBS, PP, and PPA with PPA + aPD-L1 groups, PPA@aPD-L1significantly prolonged the survival of mice with BCa and reduced tumor volume. Mechanistic studies showed that PPA inhibited the NF-κB and STAT3 signaling pathways in tumor cells. Additionally, PPA@aPD-L1increased IFN-γ and decreased IL-10 expression in bladder tumors, affecting the number and type of intratumorally infiltrating T cells. Our study presents a simple and effective drug delivery system that combines herbal monomers with ICIs. It has demonstrated a potent ability to suppress tumor growth and holds potential for future applications.

Artificial intelligence-based personalized clinical decision-making for patients with localized prostate cancer: surgery versus radiotherapy.

Surgery and radiotherapy are primary nonconservative treatments for prostate cancer (PCa). However, personalizing treatment options between these treatment modalities is challenging due to unclear criteria. We developed an artificial intelligence (AI)-based model that can identify patients with localized PCa who would benefit more from either radiotherapy or surgery, thereby providing personalized clinical decision-making. Data from consecutive patients with localized PCa who received radiotherapy or surgery with complete records of clinicopathological variables and follow-up results in 12 registries of the Surveillance, Epidemiology, and End Results database were analyzed. Patients from 7 registries were randomly assigned to training (TD) and internal validation datasets (IVD) at a 9:1 ratio. The remaining 5 registries constituted the external validation dataset (EVD). TD was divided into training-radiotherapy (TRD) and training-surgery (TSD) datasets, and IVD was divided into internal-radiotherapy (IRD) and internal-surgery (ISD) datasets. Six models for radiotherapy and surgery were trained using TRD and TSD to predict radiotherapy survival probability (RSP) and surgery survival probability (SSP), respectively. The models with the highest concordance index (C-index) on IRD and ISD were chosen to form the final treatment recommendation model (FTR). FTR recommendations were based on the higher value between RSP and SSP. Kaplan-Meier curves were generated for patients receiving recommended (consistent group) and nonrecommended treatments (inconsistent group), which were compared using the log-rank test. The study included 118 236 patients, categorized into TD (TRD: 44 621; TSD: 41 500), IVD (IRD: 4949; ISD: 4621), and EVD (22 545). Both radiotherapy and surgery models accurately predicted RSP and SSP (C-index: 0.735-0.787 and 0.769-0.797, respectively). The consistent group exhibited higher survival rates than the inconsistent group, particularly among patients not suitable for active surveillance (P < .001). FTR accurately identifies patients with localized PCa who would benefit more from either radiotherapy or surgery, offering clinicians an effective AI tool to make informed choices between these 2 treatments.