Intravitreal injections have revolutionized the treatment of retinal diseases, yet there are possible complications, such as noninfectious intraocular inflammation, a complication that may threaten vision and mimic infectious endophthalmitis. This review synthesizes current knowledge on inflammation after intravitreal therapy, with particular focus on sterile intraocular inflammation and retinal vasculitis associated with anti-VEGF agents such as brolucizumab and newer complement inhibitors like pegcetacoplan. The pathogenesis is multifactorial, involving patient-specific immune responses, drug-specific properties including aggregation or impurities, and deviations in preparation or delivery techniques. Clinical presentations range from anterior uveitis and vitritis to occlusive retinal vasculitis. Visual outcomes vary and depend on prompt recognition and appropriate management. Epidemiologic data show variable incidence across agents, with brolucizumab demonstrating higher rates of inflammation compared with ranibizumab or aflibercept. Treatment includes corticosteroids and discontinuation of the offending agent, with rare cases requiring surgical intervention. As the therapeutic landscape expands, heightened awareness and standardized evaluation of postinjection inflammation are critical to improving safety and preserving vision.

In advanced prostate cancers, the immunologically "cold" tumor microenvironment inhibiting lymphocyte infiltration has been a significant barrier to the successful application of immune checkpoint inhibitor-based therapy. In other cancer types, immunogenic cell death inducers have been shown to restore sensitivity to checkpoint inhibitor-based therapy by promoting lymphocyte infiltration and activating naïve cytotoxic T lymphocytes through cross-presentation of neoantigens by dendritic cells. Here, we describe the ability of natural product and reactive oxygen species-inducer piperlongumine to induce immunogenic cell death in prostate cancer cells and synergize with PD-1 inhibitors in the treatment of mouse prostate cancer models.

This study investigates the effects of novel matrine derivatives as heat shock protein 90 (Hsp90) inhibitors on the proliferation, cloning, and migration ability of lung cancer A549 cells along with their mechanisms. In this work, we used matrine as a lead compound with the research objectives of improving its targeting and anti-tumor activity, as well as developing Hsp90 inhibitors with novel structures. We designed and synthesized 21 matrine derivatives based on the C-14 position of matrine. The antiproliferative activities of all compounds against three types of cancer cells were determined by MTT assay. Most of the compounds showed excellent anticancer activity compared to matrine. Among them, compound H10 showed the most potent antiproliferative activity with IC50 values of 4.541 ± 0.56 µM (MDA-MB-231), 6.784 ± 0.92 µM (Huh-7), and 3.585 ± 0.45 µM (A549), respectively. Compound H10 not only effectively suppresses the colony formation and migration of A549 cells but also significantly induces cell apoptosis. Subsequent, the impact of compound H10 on Hsp90 protein and proteins associated with the PI3K/Akt/mTOR signaling pathway was evaluated using Western blot analysis. The findings demonstrated that compound H10 effectively suppresses the expression of Hsp90 and induces apoptosis in lung cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway. This study indicated that compound H10 might serve as a lead compound of Hsp90 inhibitors for the treatment of lung cancers.

Vascular endothelial growth factor (VEGF) inhibitors are associated with a high incidence of proteinuria. In patients with diabetes, increased proteinuria is closely associated with decreased renal function; however, the impact of increased proteinuria on renal function in patients with cancer and diabetes mellitus undergoing VEGF inhibitor therapy remains unknown.

The BRN2 transcription factor controls the protein expression involved in cell motility and is overexpressed in melanoma. Gene mutations involved in cell signaling pathways lead to BRN2 overexpression, tumor formation and metastasis. Peptides derived from the DNA binding domain of transcription factors can compete for the transcription binding and regulate protein expression. In this work, the antitumor activity in vitro and in vivo of the peptide E24G, derived from the DNA-binding POU domain of the BRN2 transcription factor was investigated. This peptide was fragmented into two smaller peptides E12F and A12G, their antitumor activities were characterized and compared with E24G. The E24G at 1 mM significantly reduced cell motility in vitro of B16F10-Nex2 melanoma cells. E12F peptide also inhibited cell motility at a concentration eight times smaller than E24G in murine and human melanoma cells. We observed that the antitumor activity of both E24G and E12F peptides depends on the macropinocytosis displayed by tumor cells. Also, the E24G and E12F peptides induced an increase of the CDH13 expression in 50%, however the treatment with E12F increased the expression already after 12 h by 100%. In vivo assays showed that both peptides reduced the development of metastatic lung nodules without presenting toxicity to normal organs. Our results indicate that E12F and E24G peptides can restore normal expression of BRN2 target genes at the molecular level, inhibiting the cell motility. In addition, we confirmed that the peptide binds to the DNA binding site of the BRN2 transcription factor. Further studies will elucidate their mechanisms of antitumor activity, so far our results pointed out the potential application of E12F and E24G peptides as innovative treatments for metastatic melanoma.

Long-term outcomes of patients with breast cancer have steadily improved due to advances in early detection and cancer therapeutics. Cardiovascular disease (CVD) is a leading cause of non-cancer-related mortality in this population, and this has been attributed to the cardiovascular toxicity of common breast cancer treatments including chemotherapy and radiation as well as shared risk factors between cancer and CVD. Identifying patients at risk of developing treatment-related cardiotoxicities is crucial to inform clinical decisions regarding surveillance, prevention, and management. In this review, we provide a broad overview of the treatment-related cardiotoxicities associated with common breast cancer treatment. We present data on risk-stratification tools for oncologists, including when to refer to a cardiologist, as well as recommendations for cardiovascular testing tailored to individual treatment regimens. Lastly, we review recent trial data on preventive and therapeutic approaches to treatment-related cardiotoxicities, and future directions that may lead to improved cardiovascular outcomes in this population.

PurposeThis study investigated the mechanism by which Rosmarinic acid (RA) may alleviate doxorubicin (DOX)- induced cardiomyocyte apoptosis.MethodsThe target genes of RA, DOX-related differentially expressed genes, and GEO database related genes were retrieved by bioinformatics analyses. The results of these analyses were further intersected to identify candidate genes. The protein-protein interaction network was constructed to develop the pharmacophore model. The molecular docking was simulated to determine the core target B-cell lymphoma 2-like 1 (BCL2L1) for subsequent molecular mechanism investigation in vitro. The effects of DOX and RA on the apoptosis of H9c2 cells were assessed using the CCK8 assay. The present study investigated the effect of RA on DOX-induced oxidative stress in cardiomyocytes. This investigation was conducted using an ELISA test and a DCFH-DA probe. The JC-1 probe was utilized to assess the effect of RA on DOX-induced cardiomyocyte mitochondrial membrane permeability. A Western blot assay was conducted to ascertain the activation of multiple signaling molecules, including those belonging to the BCL-2 and caspase-3 families, within the apoptosis pathway.ResultsA total of 17 differentially expressed genes (DEGs) were screened, and five genes were selected as hub DEGs. A subsequent KEGG enrichment analysis revealed that these DEGs were significantly enriched in various biological processes and pathways, including the MAPK signaling pathway, autophagy, apoptosis, and the TNF signaling pathway. The pharmacophore model and molecular docking of five candidate targets with RA were successfully established. It is noteworthy that DOX treatment led to a suppression of SOD and GSH levels, an exacerbation of oxidative stress, and a promotion of cardiomyocyte apoptosis. Furthermore, it has been demonstrated to suppress mitochondrial membrane permeability. Subsequent RT-qPCR analysis of the hub genes revealed that only BCL2L1 exhibited significant alterations. Treatment with DOX altered the expression levels of apoptosis-associated proteins, BCL-2 family members, and caspase-3 family members. However, the administration of RA mitigated the deleterious effects of DOX on cardiomyocytes.ConclusionsThe protective effects of RA may against myocardial cell apoptosis are likely mediated through its activation of BCL2L1 and inhibition of caspase cascade protein expression in myocardial cells.

Treatment with fluoropyrimidines can lead to cardiotoxicity. For 5-fluorouracil, silent myocardial ischemia and effort-related myocardial ischemia have been demonstrated. We investigated the incidence of myocardial ischemia and clinical cardiotoxicity during treatment with capecitabine, a pro-drug of 5-fluorouracil.

The tumor suppressor p53 is most commonly mutated in human cancer. The structural mutant in the β-sandwich of the protein, p53-Y220C, is the ninth most common p53 mutant. The p53-Y220C mutant has a solvent-accessible hydrophobic pocket, leading to thermal destabilization of the protein. Screening of our covalent fragment library (CovLib) revealed the highly reactive pyrazine derivatives SN006 and SN007, which arylate among other cysteines in p53, the mutation-generated Cys220. Herein, comprehensive structure-activity relationship (SAR) studies of these intrinsically reactive CovLib hits were performed, aiming to identify improved stabilizers for p53-Y220C, with a more balanced reactivity profile, diverse binding modes and a better potential for chemical optimization.

To address celastrol(Ce)'s efficacy and toxicity challenges in breast cancer, we first developed a carrier-free, self-targeting nanosystem with synergistic anti-tumor action by leveraging methotrexate (MTX)'s intrinsic folate moiety for active tumor targeting.

Breast cancer continues to be one of the most perilous diseases globally due to the challenges in identifying cost-effective and targeted targets for effective treatment strategies. In response to these unmet demands, much research has focused on investigating the anti-breast cancer properties of natural compounds due to their multi-target modes of action and favorable safety profiles. Numerous extracts of medicinal plants, essential oils, and natural bioactive substances have exhibited anticancer properties in preclinical breast cancer models. Nonetheless, the clinical utilization of therapies based on natural chemicals is constrained by challenges such as inadequate solubility and permeability. Innovative drug delivery systems utilizing nanoparticles are currently being investigated as adaptable solutions to overcome these limitations. Polysaccharide-based nanoparticles exhibit promising biodegradability and biocompatibility, making them suitable for targeted drug delivery systems among the diverse nanocarrier types. Many polysaccharide nanocarriers, including chitosan, hyaluronic acid, cellulose, starch, and complex polysaccharides, have been shown to enhance the bioavailability and therapeutic effectiveness of phytocompounds. This review examines the anticancer properties of phytocompounds and polysaccharide nanocarriers in breast cancer before focusing on the use of polysaccharide-based nanocarriers to deliver phytocompounds for the treatment of breast cancer.

To investigate the clinical features of thyroid dysfunction in lung cancer patients treated with programmed cell death receptor-1 (PD-1) or programmed cell death receptor-ligand 1 (PD-L1) and their value for predicting therapeutic efficacy.

Totally implantable venous access ports (TIVAP) are widely applied in cancer patients, primarily those requiring long-term intravenous infusion. Given the absence of clinical practice guidelines designed specifically for the use of TIVAP in cancer patients, the National Cancer Center, the Professional Committee of Interventional Oncology of Chinese Anti-Cancer Association, the Professional Committee on Minimally Invasive Intervention of World Association of Chinese Oncology, the Professional Committee of Intervention of Beijing Association of Oncology, and cancer prevention and control institutions from various provinces and cities have jointly established a guideline compilation committee comprising multidisciplinary experts. Drawing upon the latest research findings, this guideline has been formulated. It comprehensively covers the clinical application indications, preoperative preparation, intraoperative procedures, postoperative care, usage and maintenance, removal techniques, complication management, and quality control indicators related to TIVAP use in cancer patients. The recommendations were graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to ensure that the TIVAP technology can be used to serve cancer patients with greater safety and efficiency in clinical practice, thereby enhancing overall medical quality and patient satisfaction.

Microsatellite stable (MSS) metastatic colorectal cancer (mCRC) is characterized by an immunosuppressive tumor microenvironment, leading to limited efficacy of immunotherapy in these patients. Clinical trial data suggest that chemotherapy and anti-angiogenic therapy may have the potential to enhance the response to immunotherapy in these patients. However, whether these research findings can be "replicated" in clinical practice still requires further validation through real-world studies. This study aims to evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-programmed death 1 (PD-1) immunotherapy as the first-line regimen for MSS mCRC in the real world.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy, driven by the pathognomonic oncogenic fusion protein BCR::ABL1. Tyrosine kinase inhibitors (TKIs) targeting ABL1 have increased the life expectancy of patients with CML to near levels of age-matched healthy individuals. Intriguingly, the response to TKIs varies substantially and is related to observations that CML leukemic stem cells (LSCs) are less sensitive to TKIs. LSC-derived suboptimal response is suggested to explain failing treatment free remission (TFR) in approximately 60% of patients after stopping TKI treatment. Identification of novel and druggable targets on CML LSCs is a possible pathway for increasing TFR. Here we will focus on the role of CML LSCs in initial patient response to TKI therapy, and the possible interactions that LSC may experience in the bone marrow stroma. Adaptation of LSC and stroma is likely to play a central role in the heterogenous responses. Even if overall survival in CML is outstanding, deeper understanding of LSC biology may help more patients to avoid life-long therapy.

We aimed to compare the efficacy and safety of fosaprepitant plus triple therapy versus triple therapy alone, in terms of both routine and delayed regimen, in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving three-day cisplatin-based treatment.

Cancer immunotherapy enhances the prognosis of cancer patients; however, it has been shown to be associated with potentially fatal cardiac risks, which requires further confirmation. This study aimed to explore the cardiotoxicity of immune checkpoint inhibitors (ICIs) in solid tumors.

Despite significant advancements in oncology, cancer remains a leading global health burden, necessitating innovative therapeutic strategies. Here, we present a novel carrier-free tumor-targeted nanomedicine system (DPA NPs) for tumor-targeted chemoimmunotherapy, formed by self-assembly of a conjugate synthesized with doxorubicin (DOX), tumor-homing peptide iRGD, matrix metalloproteinase 2 enzyme responsive peptide (MMP2), and adjuvant monophosphoryl lipid A (MPLA). The results demonstrated that DPA NPs exhibited a stable unique 3D nanostructure with tumor microenvironment (TME)-responsive properties. DPA NPs could efficiently deliver DOX to tumor cells, inducing immunogenic cell death (ICD) and simultaneously triggering tumor specific immune response. Meanwhile, MPLA amplified the anti-tumor immunity, significantly inhibiting tumor growth and metastasis. When combined with immune checkpoint inhibitors (ICIs), DPA NPs further enhanced the therapeutic outcomes in a B16 melanoma model, demonstrating remarkable suppression of tumor growth, metastasis inhibition and recurrence prevention. Mechanistic investigations across multiple biological hierarchies conclusively further confirmed the synergistic therapeutic effect. This study demonstrated that DPA NPs provide a precise, multifunctional nanoplatform for tumor-targeted combination therapy, highlighting their potential for clinical translation in cancer treatment.

RNA-based therapies, especially small interfering RNA (siRNA), have attracted extensive attention for tumor treatment. However, most siRNA can't exert a therapeutic effect due to a lack of targeting to tumor cells and entrapment in lysosomes upon administration. To address the challenges associated with siRNA delivery, a delivery system was developed using zinc oxide nanoparticles (ZnO NPs) coated with cancer cell membranes. ZnO nanoparticles (ZnO NPs) have been recognized as effective pH-responsive nanoparticles and are widely used in the development of pH-responsive drug delivery systems. The ZnO NPs were combined with chitosan to encapsulate siRNA, allowing for dissolution in acidic lysosomes and the subsequent release of siRNA and chitosan complexes. The dissolution of ZnO NPs would also disrupt lysosomes, facilitating the escape of siRNA and enhancing its gene silencing effect. However, the chitosan and ZnO NPs nano-complexes (CS/ZnO@siRNA) were unstable in solution and lacked a specific targeting effect for tumor cells. Thus, a homologous cancer cell membrane was coated onto the nanoparticles, which has been shown to be an effective strategy for enhancing their stability and targeting capabilities. Moreover, ZnO NPs not only dissolve in acidic lysosomes to enhance the efficacy of siRNA but also elevate oxidative stress levels in cells, leading to the induction of cellular apoptosis. It was demonstrated both in vitro and in vivo that the ZnO NPs could synergistically combine with the anti-tumor siRNA (siSurvivin) to inhibit the growth of the 4T1 tumor. Altogether, the developed drug delivery system (CCM-CS/ZnO@siSurvivin) offers a new strategy for enhancing the therapeutic effect of siRNA, while synergistically inhibiting tumor growth.

Triple-negative breast cancer (TNBC) is resistant to most antitumor treatments, leaving chemotherapy as the primary option. Although doxorubicin (Dox) in combination with other therapies is promising for TNBC management, the combined effect is still compromised by the dose-limiting toxicities of Dox. Here, we developed a chemotherapeutic drug scavenger (CDS) by encapsulating GC-rich DNA-preferred binding targets of Dox-within an erythrocyte membrane functionalized with a normal tissue-targeting (NTT) peptide. Mimicking the structure of the cell nucleus, CDS selectively absorbs and neutralizes Dox in susceptible normal organs while sparing tumor tissues. This targeted detoxification allows for safe escalation of the Dox dose to 15 mg/kg, three times the standard 5 mg/kg, without observable toxicity. Such a high Dox dose enabled by CDS pretreatment significantly inhibited the post-operative residual/metastasized 4T1 tumor growth, regardless of the early or later stages of the tumor. Also, delivery of a high dose of Dox into the 4T1 tumor could profoundly increase the G2/M arrest, facilitating the combination therapy with a low-powered radiation of 2 Gy. Further, tumor exposure to high Dox amounts could convert the 4T1 tumor microenvironment from 'cold' to 'hot', leading to improved infiltration of immune cells, including T cells, dendritic cells, and macrophages. Overall, this study demonstrates how the safe injection of high amounts of Dox enabled by CDS detoxification could augment and extend Dox's functionality combined with surgery, radiotherapy, and cell therapy for TNBC treatment.