Zebrafish xenotransplantation is a pivotal technique for investigating human cancer pathogenesis and predicting individual drug responses. This document introduces a streamlined protocol (ZefiX) for expanding primary B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patient samples or immortalized cell lines in transiently immunosuppressed zebrafish embryos, utilizing flow cytometry for high-resolution single-cell analysis of treatment responses. Compared to solid tumor engraftments, leukemia cells profit significantly from a morpholino antisense oligonucleotide-based suppression of macrophage and neutrophil differentiating factors during the assay. Flow cytometry analysis of dissociated graft cells enables precise evaluation of cell count, proliferation rate, and vitality after treatment on a per-cell basis. This approach has been validated using targeted therapeutics such as venetoclax and dasatinib, with treatment outcomes compared to clinical records of related patient samples and traditional 2D culture controls. Notably, the protocol is completed within 7 days, aligning with clinical decision-making timelines. The methodology is adaptable for testing selected drugs in various cancer types, including solid tumors, thereby supporting personalized therapeutic strategies. However, limitations on the number of drugs that can be assessed, likely due to pharmacokinetic constraints in zebrafish embryos, should be considered.

Chronic inflammation plays a crucial role in the development and progression of rheumatoid arthritis (RA). Prostate cancer with bone metastasis (PCa-BM) is the most common metastatic form of advanced prostate cancer in the elderly, significantly affecting prognosis and quality of life Although chemotherapy is commonly used for PCa-BM, the chronic inflammation it causes may exacerbate the risk of joint injuries to induce RA and related complications. Therefore, exploring the risk of chemotherapy-induced chronic inflammation on RA risk in PCa-BM patients holds critical importance.

Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor characterized by poor prognosis and limited treatment options. Despite current therapies combining surgery, radiotherapy, and chemotherapy, GBM remains highly resistant to treatment, largely due to the challenges of drug delivery across the blood-brain barrier (BBB). Nanoparticles (NPs) have shown promise as drug carriers, but their clinical translation is hindered by limited brain accumulation and rapid clearance by the immune system. In this study, we explored the potential of GBM cell membrane (CM)-coated NPs (G-NPs) as a strategy to improve GBM targeting and, therefore, efficient treatments. We optimized the CM isolation protocol using U87-MG human GBM cells and identified the Heidolph homogenizer as the most effective technique for producing pure, enriched CM fractions, proposing it as a standard method due to its high scalability. G-NPs were extensively characterized, demonstrating excellent colloidal stability under biological conditions. Flow cytometry revealed the enhanced uptake of G-NPs by U87-MG cells compared to non-coated NPs. Notably, the specific homotargeting capability of G-NPs toward human glioblastoma cells was ultimately confirmed by demonstrating a marked specificity of the glioblastoma CM coating when compared to human fibroblast CM-coated NPs, highlighting selective tumor cell-type targeting. Additionally, the coating of NPs with GBM CMs not only did not impede the physiological passage of NPs across the human in vitro BBB, but interestingly, increased the BBB permeability to G-NPs. These findings highlight that biomimetic coating of NPs with GBM cells is a potential strategy to create platforms for the targeted chemotherapy of GBM.

Circadian rhythm (CR) disruption has been confirmed as a contributing factor to tumor progression. However, regulating circadian genes shows an inhibitory effect on ovarian tumor initiation and progression, which highlights the urgent necessity to regulate tumors' CR to understand their role in ovarian cancer (OC) therapy precisely. Herein, a novel near-infrared (NIR) light-controlled spatiotemporal strategy is presented, aiming to manipulate ovarian tumors' CR while enhancing the efficacy of chemotherapy agents. To achieve this strategy, a versatile nanoplatform (NPPEG-CS) that integrates the modified photothermal sensitizer IR-820 and a norcantharidin-platinum(IV) prodrug conjugate onto a cationic polyethylenimine (PEI) backbone coated with PEG-modified chondroitin sulfate (PEG-CS) for targeted delivery to ovarian tumors is designed. NPPEG-CS effectively diminishes the CR amplitude upon NIR illumination, demonstrating its potential for innovative cancer treatment strategies. Additionally, molecular analyses reveal that this disruption involves calcium-mediated influx, triggered by the photothermal properties of NPPEG-CS. When combined with chemotherapeutic agents, a disrupted clock can elevate tumor sensitivity to these drugs. This process effectively increases DNA-Pt adducts, reduces the activity of protein phosphatase 2A (PP2A), and promotes cell cycle arrest, synergistically amplifying DNA damage and inducing robust tumor apoptosis. The novel nanoparticle synergism offers innovative insights into harnessing CR as a therapeutic target for more effective cancer management.

Magnetic nanoparticle-based targeted hyperthermia, combined with chemotherapy, is a promising approach for cancer treatment. In this study, a targeted magnetic drug delivery system was developed, comprising doxorubicin (DOX), a [D-Trp6] luteinizing hormone-releasing hormone (LHRH) (Triptorelin) ligand, and a polyethylene glycol (PEG)-coated magnetite core, aiming to enhance cancer therapy efficacy. Fourier-transform infrared spectroscopy confirmed the conjugation of LHRH onto the PEG-coated Fe3O4 nanoparticles. Ultraviolet-visible spectroscopy was employed to assess drug loading, revealing a loading efficiency of 66%. The DOX-loaded, LHRH-tagged PEG-coated Fe3O4 nanoparticles were evaluated for their cytotoxic effects on A549 and MCF-7 cancer cell lines under three treatment modalities: thermotherapy, chemotherapy, and combined thermo-chemotherapy, both with and without the application of a magnetic field. Cell viability was assessed using the 2,5-diphenyltetrazolium bromide (MTT) assay. In A549 cells, the combined thermo-chemotherapy treatment at a DOX concentration of 10 μg/ml resulted in an 88% reduction in cell viability, outperforming chemotherapy alone (62%) and thermotherapy alone (47%). Similarly, in MCF-7 cells, the combined treatment at 8 μg/ml DOX led to a 91% reduction in viability, surpassing the effects of chemotherapy (57%) and thermotherapy (45%) individually. Additionally, the targeted DOX-loaded nanoparticles significantly elevated interferon-gamma production, indicating an enhanced immune response and increased cancer cell apoptosis.

Although the presence of Kirsten murine sarcoma virus (KRAS) mutations predicts a failure of non-small cell carcinoma (NSCLC) patients to benefit from epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy it may be more sensitive to programmed combination therapy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors + anti-angiogenesis. Recent treatment guidelines and clinical studies related to adenocarcinoma in NSCLC have indicated that in patients with inoperable stage IV lung adenocarcinoma, immune checkpoint inhibitors in combination with anti-angiogenic drugs may exert a synergistic effect and significantly improve the efficacy of near-term treatment, but quantification and long-term follow-up of specific clinical indicators are still lacking. No previous cases of long-term good results with camrelizumab combined with anti-angiogenic agents for KRAS-mutated NSCLC have been described.

Immune checkpoint inhibitor (ICI) monotherapy elicits limited intrahepatic responses in patients with advanced hepatocellular carcinoma (HCC). Here, we investigate the organ-specific objective response rate (OSORR) of nivolumab plus ipilimumab (Nivo/Ipi) combination treatment, considering prior ICI exposure, compared with nivolumab (Nivo) monotherapy.

Glioblastoma (GBM) is a malignant tumor that currently still faces challenges for a complete cure. Although GBM treatment has made great progress, the prognosis of patients is still poor due to interference of various factors in treatment such as the blood-brain barrier (BBB), grade malignancy, intra- and intertumor heterogeneity, drug resistance, and poor targeting of anti-tumor drugs. In recent years, with marked advances in nanotechnology, different types of nanodrug delivery systems have been developed and have been considered as a promising therapeutic measure to gradually overcome chemotherapy resistance and improve tumor targeting. Carbon dots (CDs), as a new type of therapeutic NP, have become a research hotspot of concern for many researchers in recent years. NPs based on CDs have high modifiability and functionalization, allowing for covalent binding with chemotherapy drugs, genes, immune cells and photosensitizers, effectively targeting tumor cells and reducing peripheral cytotoxicity. However, at present, CDs are still in the basic research stage or the preclinical exploratory research stage, and has not yet entered the clinical trial stage or the implementation and application stage. Here, we review the fundamental principles of CDs in the broader field of nanotechnology, their development history, classification, synthesis, and potential for tumor treatment. Especially in the treatment of cancer, CDs can not only participate in photodynamic therapy, photothermal therapy, sonodynamic therapy, chemodynamic therapy, and chemotherapy, but also in multi-modal combination therapy. Here, we hope to provide some insights for further research.

The monoclonal antibodies consist of an innovative form of immunotherapy, capable of defeating several diseases, such as cancer. It is an emergent and important theme, that advances evaluation, challenges, and future perspectives with high relevance to identify gaps in recent studies and to consolidate this general theme in only one research. Its action in Chronic and Acute Lymphoid Leukemia has been evaluated in several clinical trials, which were selected between 2022 and 2023, in order to understand better the monoclonal antibodies that were most studied. The biopharmaceutical compounds Ibrutinib, Obinutuzumab, Rituximab, Venetoclax, and Inotuzumab Ozogamicin were the ones that most appeared in the most recent publications, indicating the importance of amplifying the studies. The action mechanisms that are used imply that their combined use has more success in the disease remission, showing a lower recurrence, adverse effects, and toxicity. Besides the adverse effects and overwhelming prices of the treatment, these immunotherapies results are promising, amplifying the survival rates, improving the patient's life quality, and resulting in a precision medicine, aiming a custom treatment. The future perspectives on this therapy consist of its application in the public health system, with patients being able to be submitted to this treatment without any costs and receive a better life quality.

Apatinib has been reported to be a promising treatment for sorafenib-resistant hepatocellular carcinoma (HCC) patients. However, the underlying mechanism remains ambiguous. The study aimed to explore the efficacy of apatinib in sorafenib-resistant HCC and the underlying mechanism both in vitro and in vivo.

The cell cycle is a tightly coupled series of events that enable cells to grow and proliferate. Cyclin-dependent kinases (CDKs) play crucial roles in the cell cycle by enabling cells to transition between different phases when they are activated. Cell cycle proteins enhance the activity of CDKs, while natural CDK inhibitors (CDKIs) suppress them. The cell cycle continues in cycles under normal conditions, but when conditions change, cells halt or terminate the cell cycle. Tumors are tissues that grow out of control, and the mechanisms of various types of tumors are different; however, almost all tumor cells share several common characteristics, including proliferation, prevention of apoptosis and genomic instability. Cellular division is essential in the progression of cancer. A key characteristic of cancer is the uncontrolled growth of tumor cells, which is due to the erratic behavior of several proteins during the cell cycle. Therefore, cell cycle regulators are considered attractive targets for the treatment of cancer. The present analysis highlights proteins that play a direct role in controlling the tumor cell cycle, such as CDKs, and provides a brief overview of checkpoint kinases. The present review also discusses how cell cycle proteins contribute to cancer and describes some of the antitumor drugs that are being researched.

Triphenylphosphine (TPP) and Doxorubicin (DOX) were conjugated to obtain Triphenylphosphine-Doxorubicin (TPP-DOX), which was applied in tumor cells for enhancement of DOX in mitochondria targeting. The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.

The combination of anti-angiogenic agents, PD-1/L1 inhibitors, and hepatic arterial infusion chemotherapy (HAIC) has emerged as an important strategy for unresectable hepatocellular carcinoma (uHCC), yet comparative data on efficacy and safety between different anti-angiogenic agents (lenvatinib [LenHAP] or bevacizumab [BevHAP]) remain lacking, especially in patients with potential resectable features (PotenR).

Cytarabine (Ara-C) is a cornerstone of acute myeloid leukaemia (AML) treatment, particularly in consolidation therapy. Although high-dose cytarabine (HDAC) has been widely adopted for consolidation in AML, intermediate-dose cytarabine (IDAC) is increasingly favoured due to its comparable efficacy and improved tolerability. However, the potential benefit of combining another agent with IDAC during consolidation therapy has yet to be adequately validated.

The nucleoside analogue 6-thio-2'-deoxyguanosine (6-thio-dG, also known as THIO) is a telomere-targeting agent with important clinical potency. It can selectively kill telomerase-positive tumor cells. We previously reported that THIO could successfully induce immunogenic cell death (ICD) in multiple mouse tumor cell lines. In this study, we further explored the potential impact of THIO on remodeling the tumor microenvironment, regulating anti-tumor immune responses, and its possible synergistic effects with other therapeutic methods, such as tumor vaccines. Our results showed that THIO could also induce ICD in various human tumor cell lines. The induction of ICD in tumor cells promoted the migration and maturation of antigen-presenting cells. Administration of THIO significantly inhibited the growth of established CT26 and TC-1 tumors in mice. Meanwhile, it enhanced the anti-tumor CTL response and reduced the levels of immunosuppressive myeloid-derived suppressor cells (MDSCs) in both the spleen and tumor tissues. Additionally, THIO had a direct inhibitory effect on the proliferation and differentiation of MDSCs. Moreover, when combined with bacterial biomimetic vesicles or a nanovaccine, such as THIO with BBV or different Q11-tumor antigen peptide nanofibers, it exhibited enhanced anti-tumor effects and immune responses compared to monotherapy in either "immune hot" TC-1 tumors or "immune cold" B16-F10 tumors. In summary, THIO has the ability to remodel the tumor microenvironment, exert a specific killing effect on tumor cells, and effectively cooperate with tumor vaccines. This broadens the anti-tumor mechanisms of THIO and provides a promising strategy for improving anti-tumor immunotherapies.

Breast cancer is a major cause of mortality among women worldwide, with triple-negative breast cancer (TNBC) presenting a particularly serious clinical challenge due to its low survival rates and high likelihood of recurrence. Despite the availability of several treatment options, more effective and targeted therapies are urgently needed. Chloroquine (CQ), a well-known anti-malarial drug, has recently emerged as a potential anti-cancer agent and chemo sensitizer when combined with other treatments. In this study, we evaluated the anticancer effects of CQ on MDA-MB-231 cells, a human TNBC cell line. Cells were treated with varying concentrations of chloroquine (CQ), and cell viability was assessed using the MTT assay, resulting in an IC₅₀ value of 113 μg/mL with 87.28% inhibition. Additional analyses including DAPI staining flow cytometry for cell cycle analysis, trypan blue exclusion and LDH leakage and scratch wound healing assays were performed to assess cytotoxicity, proliferation, and cell migration. The results demonstrated that CQ significantly reduced cell viability and effectively inhibited the proliferation, migration, and invasion of MDA-MB-231 cells. This novelty of this study was potential of chloroquine as a promising therapeutic agent for the treatment of TNBC.

The clinical effectiveness of wide range of currently available anticancer drugs is being reduced .HIF-1 alpha is essential for the reprogramming of cancer cells' metabolism,so cancer treatments include inhibiting the HIF-1α signaling pathway and The evidence underscores the potential of natural flavonoids as HIF-1α inhibitors in cancer therapy.

Immune checkpoint inhibitors (ICIs) have an expanding role in the management of numerous cancers. Hyperglycaemia is commonly seen in patients treated with ICIs. However, the differential diagnosis for hyperglycaemia is broad, and incorrect diagnosis can have serious consequences. Herein we review the available literature on causes of hyperglycaemia in ICI treated patients and expert guidelines on management and provide an updated synthesis of expert multidisciplinary recommendations. Our key recommendations are as follows: Intensity of screening for hyperglycaemia should be based on a patient's risk level, including assessment of factors such as corticosteroid use, pre-existing diabetes, baseline HbA1c and fasting blood glucose levels (BGL). People with new onset hyperglycaemia should undergo initial assessment to determine severity and aetiology, including bedside capillary BGL, and formal bloods including lipase, C-peptide with matching glucose, electrolytes and renal function and in some cases type 1 diabetes autoantibodies. People with BGL >15mmol/L (or those receiving SGLT2 inhibitors with BGL >10mmol/L) should additionally have ketones measured. Patients with a high risk of diabetic ketoacidosis (BGL>15 mmol/L, ketones >2 mmol/L) and/or risk of hyperosmolar hyperglycaemic state (BGL persistently >20 mmol/L or reading 'HI') should be referred directly to hospital for emergency assessment and management. Further management of hyperglycaemia should be tailored to the underlying cause(s).

Sulfate polysaccharides (SPS) are polysaccharides with highly anionic properties due to of the binding of negatively charged sulfate groups to the central sugar backbone. This study aims to structurally elucidate and functionally evaluate a natural SPS purified from fraction 2 of SPS of 50 mM ammonium sulfate feeding of A. cinnamomea, noted as N50 F2. N50 F2 exhibited a high sulfate content of 3.89 mmol/g demonstrated excellent anti-cancer activity. Its anti-inflammatory effect is mediated by down-regulating AKT phosphorylation and reducing TGFRII expression in LPS-induced macrophage cells. The anti-cancer activity of N50 F2 is achieved through the down-regulation of the phosphorylation of AKT/ERK/EGFR/FAK and the inhibition of slug, TGFRI, and TGFRII's expression. N50 F2 also activated apoptotic related molecules of CHOP, and cleavage PARP, caspase 3 in lung cancer cells. Structural delineation demonstrated that N50 F2 was a sulfated α-1,4-linked galactoglucan, with a glucosyl branch on the 3-O position of one skeleton moiety and a galactosyl on the 6-O position of another, with sulfate substitutions on all the hydroxy positions. This study offers a reliable production method for SPS and highlights the potential of SPS for pharmaceutical applications.

Mushroom-derived polysaccharides are known for their diverse biological activities, including immunomodulatory and anticancer properties. Breast cancer, the leading cause of cancer-related death among women worldwide, lacks targeted molecular therapies, underscoring the need for novel therapeutic agents. In this study, we extracted, purified, and characterized a novel heteropolysaccharide (HTP) - a rhamnogalactan - composed of galactose (72.6 %) and rhamnose (27.4 %) from the edible mushroom Lactarius quieticolor. Structural analysis revealed that HTP consists of a (1 → 6)-linked α-d-galactopyranose backbone, heavily substituted at O-2 by non-reducing rhamnose units, with a weight-average molar mass of 2.41 × 104 g.mol-1. In vitro assays using a triple-negative breast cancer (TNBC) cell model - the most aggressive subtype - showed a significant reduction in cell viability (50 % at 1200 μg·mL-1). Furthermore, an additive effect was observed when co-administered with the chemotherapy drug paclitaxel, reducing the cell viability to 42 %. These findings suggest potential therapeutic applications of the purified mushroom rhamnogalactan reported in this study against TNBC.