Cancer cells drive the increase in vascular permeability mediating tumor cell extravasation and metastatic seeding. VIAN-c4551, an antiangiogenic peptide analog of vasoinhibin, inhibits the growth and vascularization of melanoma tumors in mice. Because VIAN-c4551 is a potent inhibitor of vascular permeability, we evaluated whether its antitumor action extended to a reduction in metastasis generation.

Linezolid, an oxazolidinone antibiotic, is widely used to treat multidrug-resistant tuberculosis and drug-resistant Gram-positive infections. However, prolonged use is associated with severe hematologic toxicity, the underlying mechanisms of which remain incompletely understood, particularly regarding the role of linezolid metabolites. Our clinical study indicates that elevated exposure to PNU142586, a primary metabolite of linezolid, is associated with an increased risk of linezolid-induced toxicity, even in the absence of renal impairment. To elucidate its mechanism, we identify DNA topoisomerase 2-α (TOP2A) and DNA topoisomerase 2-β (TOP2B) as primary targets of PNU142586 at molecular, cellular, and in vivo levels. PNU142586 disrupts replication and transcription by impeding DNA binding to TOP2A and TOP2B with a favorable conformation for cleavage and by inhibiting adenosine 5'-triphosphate hydrolysis, ultimately leading to antiproliferative and cytotoxic effects, including mitochondrial dysfunction. The present study thus provides mechanistic insight into linezolid-induced hematologic toxicity and offers a foundation for safer antibiotic development and improved clinical monitoring through biomarker identification.

Follicular lymphoma (FL) patients have achieved favorable long-term survival since the introduction of rituximab. However, the development of second primary malignancies (SPMs) indicates a poor survival prognosis for FL patients, and large-scale studies in this field remain limited. This study investigates the prognostic factors for FL patients in the rituximab era, as well as the clinical characteristics, risk factors, and prognosis for patients who developed SPMs.

Immune checkpoint inhibitors (ICIs) have significantly improved the overall survival of patients with many different types of cancer since they were first approved by the United States in 2011. However, patients who are treated with ICIs can develop a variety of toxicities, known as immunotherapy-related adverse events (irAEs), that have the potential to affect essentially any organ system. Due to the growing use of ICIs in the field of oncology, it is likely that non-oncologist clinicians will increasingly encounter irAEs in both inpatient and outpatient environments. This review will provide an overview of both common and rare irAEs for the non-oncologist clinician, in addition to providing information about several guidelines developed by multiple organizations that can aid the non-oncologist clinician with the initial work-up and diagnosis of irAEs.

Costus speciosus is a medicinal plant with a long history in Indian Ayurvedic medicine, recognized for its diverse bioactive properties, including antibacterial, anticancer, anti-inflammatory, and antidiabetic effects. This review highlights its therapeutic potential, particularly in cancer treatment, where its bioactive compounds exhibit cytotoxic effects against breast, ovarian, and uterine cancers. These compounds have shown the ability to induce apoptosis, regulate the cell cycle, and inhibit cancer progression, offering a promising alternative to conventional chemotherapy with potentially fewer side effects. Additionally, C. speciosus demonstrates antioxidant, antimicrobial, and antidiabetic properties, expanding its clinical applications. Despite its promising pharmacological profile, further research is required to understand the molecular mechanisms underlying its therapeutic effects and ensure the safety and efficacy of its various extracts for therapeutic use.

Cancer therapeutic vaccines are used to strengthen a patient's own immune system by amplifying existing immune responses. Intralesional administration of the bacteria-based emm55 vaccine together with the PD1 checkpoint inhibitor produced a strong anti-tumor effect against the B16 melanoma murine model. However, it is not trivial to design an optimal order and frequency of injections for combination therapies. Here, we developed a coupled ordinary differential equations model calibrated to experimental data and used the mesh adaptive direct search method to optimize the treatment protocols of the emm55 vaccine and anti-PD1 combined therapy. This method determined that early consecutive vaccine injections combined with distributed anti-PD1 injections of decreasing separation time yielded the best tumor size reduction. The optimized protocols led to a twofold decrease in tumor area for the vaccine-alone treatment, and a fourfold decrease for the combined therapy. Our results reveal the tumor subpopulation dynamics in the optimal treatment condition, defining the path for efficacious treatment design. Similar computational frameworks can be applied to other tumors and other combination therapies to generate experimentally testable hypotheses in a fairly unrestricted and inexpensive setting.

Intra-arterial chemotherapy (IAC) has emerged as the primary treatment option for retinoblastoma management. It enables the localized delivery of a higher concentration of chemotherapeutic agents (melphalan, carboplatin and topotecan) in the ophthalmic artery, enhancing tumour control and potentially avoiding the need for enucleation. Nevertheless, procedure-related complications have raised concerns. In this article, we outline the various technical considerations for performing safe IAC and minimizing procedure-related complications.

Millipore filters are routinely used in vitreous surgeries for loading intraocular gas. This study purports to establish feasibility of in-line Millipore filter as a filtration barrier and rationalize their use during intravitreal antivascular endothelial growth factor (antiVEGF) injection to reduce the risk of endophthalmitis.

Recent advances in deep learning and machine learning have greatly increased the capabilities of extracting features for evaluating the response to anti VEGF treatment in patients with Diabetic Macular Edema (DME). In this review, we explore how these algorithms can be used for discriminating between responders and non-responders to anti vascular endothelial growth factor (VEGF) injections. Electronic databases, including PubMed, IEEE Xplore, BioMed, JAMA, and Google Scholar, were searched, and reference lists from relevant publications were also considered from inception till August 31, 2023, based on the inclusion and exclusion criteria. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The results focus on keywords such as DME, OCT, anti VEGF, and patient responses after anti VEGF injections. The article measures the effectiveness of different machine learning and deep learning algorithms, including linear discriminant analysis (LDA), ResNet-50, CNN with attention, quadratic discriminant analysis (QDA), random forest (RF), and support vector machines (SVM), in analyzing eyes that could tolerate extended interval dosing. According to a review of 50 relevant papers published between 2016 and 2023, the algorithms achieved an average automated sensitivity of 74% (95% CI: 0.55-0.92) in detecting treatment responses.

Platinum (Pt) drugs are widely utilized in cancer chemotherapy. Although cytotoxic and resistance mechanisms of Pt drugs have been thoroughly explored, it remains elusive what factors affect the receptiveness of DNA to drug-induced damage in nuclei. Here, we demonstrate that nuclear locations of chromatin play a key role in Pt drug-induced DNA damage susceptibility in vivo. By integrating data from damage-seq experiments with 3D genome structure information, we show that nuclear locations of chromatin relative to specific nuclear bodies and compartments explain patterns of cisplatin DNA damage susceptibility. This aligns with observations of cisplatin enrichment in biomolecular condensates at certain nuclear bodies. Finally, 3D structure mapping of DNA damage reveals characteristic differences between nuclear distributions of oxaliplatin-induced DNA damage in drug resistant versus sensitive cells. DNA damage increases in gene-poor chromatin at the nuclear periphery, while it decreases in gene-rich regions located at nuclear speckles. This suggests a strategic redistribution of Pt drug-induced damage in nuclei during chemoresistance development.

Although a dosage decrease regimen for chronic phase chronic myeloid leukemia (CML-CP) has been suggested, there is a marked lack of guidance on individualizing medication dosages for patients.

Antibody-drug conjugates (ADCs) have emerged as a transformative therapeutic modality in oncology, offering unprecedented precision in targeting tumor cells while sparing healthy tissues. In bladder cancer, a malignancy with high recurrence rates and limited treatment options, ADCs have demonstrated remarkable efficacy by targeting specific tumor-associated antigens such as NECTIN-4 and Human Epidermal Growth Factor Receptor 2 (HER2). This review provides a comprehensive evaluation of the current landscape of ADC-based therapies for bladder cancer, focusing on their mechanisms of action, clinical efficacy, and safety profiles.

Pancreatic cancer, a highly lethal malignancy with limited therapeutic options, necessitates the identification of novel prognostic biomarkers and therapeutic targets. The extracellular matrix protein vitronectin (VTN) has been implicated in tumor progression, but its specific role in pancreatic cancer progression and immunotherapy response remains unclear.

Tumor immunotherapy has revolutionized cancer treatment, particularly through the use of immune checkpoint inhibitors targeting the PD-L1/PD-1 axis. While PD-L1 expression on tumor cells is an established predictive biomarker for therapeutic response, emerging evidence highlights the importance of PD-L1 expression on myeloid cells, both in the periphery and within the tumor microenvironment (TME). This study explores the immunomodulatory effects of the selective HDAC6 inhibitor ITF3756 on monocytes and dendritic cells (DCs).

Lung cancer remains a leading cause of cancer-related mortality, necessitating improved treatment strategies. This study collectively highlights the valuable potential of marine sponges as a source for discovering new anti-tumor agents.

Alleviating the toxic and adverse reactions associated with chemotherapy is crucial for improving patient outcomes. This study aimed to assess the impacts of positive emotion, engagement, relationships, meaning, and accomplishment (PERMA) model-based psychological interventions and predictive chemotherapy reaction nursing on patients with malignant tumors following chemotherapy.

Preliminary data from the MorningSun study have demonstrated that outpatient subcutaneous mosunetuzumab can be safely administered.

African Swine Fever Virus (ASFV) Topo II ATPase domain, resistant to conventional inhibitors (e.g., ICRF-187) due to M18/W19 steric clashes, was targeted via hierarchical virtual screening (Schrödinger) of the Chembridge library combined with MM/GBSA calculations. Five ligands (10012949, 40242484, 46712145, 15880207, and 33688815) showed high affinity, with 46712145 adopting symmetrical π-π stacking, hydrogen bonds, and alkyl interactions to bypass steric hindrance. Molecular dynamics simulations (100 ns) revealed ligand-induced flexibility, evidenced by elevated RMSD/Rg values versus the free protein. DCCM analysis highlighted enhanced anti-correlated motions between GHKL motifs and sensor domains in chain B/C, suggesting stabilization of a non-catalytic conformation to inhibit ATP hydrolysis. Free energy landscape (FEL) analysis showed 46712145 occupying a broad, shallow energy basin, enabling conformational adaptability, contrasting the narrow deep well of the free protein. This study proposes a symmetric ligand design strategy and conformational capture mechanism to block ATPase activity. Compound 46712145 demonstrates stable binding and dynamic regulation, providing a novel lead scaffold for anti-ASFV drug development. These findings establish a structural framework for combating ASFV through targeted ATPase inhibition.

The synthesis and antimicrobial and anticancer activity of 3,3'-((3-hydroxyphenyl)azanediyl)dipropionic acid derivatives (2-25) against drug-resistant bacterial pathogens and FaDu head and neck cancer cells were investigated. The derivatives were synthesized through various methods, including esterification, hydrazinolysis, and condensation reactions. The compounds demonstrated structure-dependent antimicrobial activity, predominantly targeting Gram-positive pathogens. Compounds containing 4-nitrophenyl, 1-naphthyl, and 5-nitro-2-thienyl groups exhibited enhanced activity against S. aureus and E. faecalis. Additionally, compounds 5, 6, and 25 showed antiproliferative activity in cisplatin-resistant FaDu cells at low micromolar concentrations. The in silico modeling revealed that compound 25 interacts with the HER-2 and c-MET proteins. These compounds also induced significant oxidative stress in FaDu cells and demonstrated low cytotoxic activity in non-cancerous HEK293 cells. These results highlight the potential of N-aryl-substituted β-amino acid derivatives as promising scaffolds for the further development of novel amino acid-based antimicrobial and anticancer agents targeting drug-resistant pathogens and cancers.

Imidazole is a five-membered heterocyclic system featuring two nitrogen heteroatoms at the 1- and 3-positions of the ring. The imidazole scaffold is particularly suited for kinase inhibition concepts. This further confirms that this scaffold is a privileged structure in the development of anticancer drugs. Considering these key factors and the recent focus of scientists on imidazole compounds, we discuss the anticancer activities of imidazole-containing hybrids and related compounds, highlighting articles published in 2023 that serve as a basis for medicinal chemistry leads. From a chemical perspective, the present review emphasizes hybrid molecules with an imidazole ring in the side chain, imidazole-centered hybrid molecules, condensed imidazole hybrids, hybrid compounds containing two or more imidazole rings, polycyclic imidazole hybrids, imidazole-containing metal complexes, and benzimidazole hybrids.