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.

Cancer remains a leading global health challenge, driving the search for effective and targeted therapies. This review explores the potential of pectin-based nanoparticles in cancer treatment, emphasizing their role as a promising biomaterial in nanoparticle formulation. The review begins by discussing the structure, properties, and extraction methods of pectin, highlighting its biocompatibility and biodegradability, which are crucial for novel drug delivery systems. The review further delves into the manufacturing techniques of pectin-based NPs and examines various targeting strategies, including passive mechanisms like the surged permeability and retention effect, and active approaches such as ligand-mediated targeting. Strategies for overcoming biological barriers are also discussed. The review also entails the application of pectin NPs to treat different type of cancers, including breast, lung, brain, liver, and pancreatic cancers, underscoring their potential to enhance the therapeutic outcomes and minimise adverse effects. This review provides insights into the advancements and future directions of pectin-based NPs in oncology.

Preserving plant biodiversity and making sustainable use of genetic resources in agriculture is a topical issue with ecological, economic, and social repercussions. In Italy, some onion (Allium cepa L.) varieties, only cultivated by local farmers, are neglected and worth to be valorised. In this work, a comparative chemical and biological study of nine onion varieties and four commercially available ones was carried out by combining the acquisition of large, high-resolution experimental datasets (LC-HR -ESI-MS2) with molecular networking strategy and chemometric tools. All extracts were investigated for antioxidant properties and antiangiogenic activity by two in vivo models, chick chorioallantoic membrane (CAM), and zebrafish embryos. 'Ciatta', 'Massese', and 'Fiorentina' indigenous varieties showed potent inhibitory effects on blood vessel formation, comparably with the commercial reference variety 'Tropea'. The bioactive profile rich in phenols, alkaloids, saponins, and fatty acids of these varieties revealed their health-promoting potential and importance for the agri-food chain.

As possible delivery systems for anticancer medications and molecular imaging, polymer nanoparticles have tremendous potentials. This study aimed to develop a novel drug delivery system using PTX conjugated β-cyclodextrin inclusion complex-capped gold nanoparticles (PTX-β-CD-AuNPs) to manage triple-negative breast cancer (TNBC). Characterization techniques confirmed the successful synthesis of PTX-β-CD-AuNPs with mean size of around 43 nm. In vitro studies demonstrated enhanced cytotoxicity of PTX-β-CD-AuNPs compared to the individual components, as evidenced by MTT assay results. Furthermore, morphological analysis revealed significant alterations in cancer cell morphology, including cytoskeletal disruption and apoptosis induction. The clonogenic assay demonstrated the ability of PTX-β-CD-AuNPs to suppress colony formation, indicating potential targeting of cancer stem cells. Additionally, migration assays showed reduced cell migratory capacity, suggesting potential anti-metastatic effects. These findings illustrate the efficacy of PTX-β-CD-AuNPs as a promising nanocarrier for treating TNBC. To assess the therapeutic efficacy of PTX-β-CD-AuNPs and clarify the mechanisms behind it, additional study is essential.

Depicting a global landscape of essential gene-targeting drugs would provide more opportunities for cancer therapy. However, a systematic investigation on drugs targeting essential genes still has not been reported. We suppose that drugs targeting cancer-type-specific essential genes would generally have less toxicity than those targeting pan-cancer essential genes. A scoring function-based strategy was developed to identify cancer-type-specific targets and drugs. The EssentialitySpecificityScore ranked the essential genes in 19 cancer types, and 1151 top genes were identified as cancer-type-specific targets. Combining target-drug interaction databases with research/marketing status, 370 cancer-type-specific drugs were identified, bound to 100 out of all identified targets. Profiles of applied cancer types of identified targets and drugs illustrate the scoring strategy's effectiveness: most drugs apply to cancer types <10. Seven drugs with no previous anticancer evidence were validated in 11 lung adenocarcinoma cell lines, and lower inhibition rates (from 9.4% to 44.0%) were observed in 10 normal cell lines. This difference is statistically significant (Student's t-test, P ≤ .0001), confirming the rationality of our supposition. Our built EGKG (Essential Gene Knowledge Graph) forms a computational basis to uncover essential gene targets and drugs for specific cancer types. It is available at http://gepa.org.cn/egkg/. Also, our experimental result suggests that combining drugs with orthogonal essentiality may be an alternative way to improve anticancer effects while maintaining biocompatibility. The code and data are available at https://github.com/KKINGA1/EGKG_data_process.

Consolidative PD-L1 inhibitors after concurrent chemoradiotherapy (cCRT) have become standard care in locally advanced non-small cell lung cancer (LA-NSCLC). However, the correlation between immune-related adverse event (irAE) characteristics and patient outcomes remains unclear.

Menaquinone (MK), which is also known as vitamin K2, is a kind of lipoquinone that, unlike humans, is biosynthesized in bacteria through a series of steps as a necessary component of their respiratory chain for electron transport among various components of the bacterial cell membrane. MKs are receiving increasing attention as they play several essential biological roles in humans.

Resistance limits the efficacy and durability of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). Therefore, we conducted a retrospective cohort study to investigate the outcomes and characteristics of HCC patients with resistance to immunotherapy. Patients with HCC who have received ICIs at Eastern Hepatobiliary Surgery Hospital between 2016 and 2021 were retrospectively screened and divided into primary resistance, secondary resistance, and durable response group. Time to progression (TTP), overall survival (OS), subsequent management and post-progression survival (PPS) were analyzed. Of 496 patients included, 229 (46.2%) and 141 (28.4%) patients developed primary and secondary resistance, and 126 (25.4%) patients achieved a durable response, the median TTP was 2.83 [2.56-3.09] months, 11.93 [10.45-13.40] months, and not reached, respectively, whereas the median OS was 12.83 [10.36-15.30] months, 31.53 [28.09-34.97] and not reached, respectively. Multivariate logistic regression revealed that Child-Pugh score, BCLC stage, and combined systemic therapies (ICI plus bevacizumab or lenvatinib versus ICI monotherapy) were independently associated with primary resistance, and only combined systemic therapies (ICI plus bevacizumab versus ICI monotherapy) were independently associated with secondary resistance. AFP levels were independently associated with PPS in patients with primary resistance, while post-progression therapies (ICI-based therapies versus others) were independently associated with PPS in patients with resistance. The risk of resistance was notably lower in patients receiving the combination of ICI plus bevacizumab. High AFP levels were associated with the survival of patients with primary resistance. ICI-based maintenance therapy after resistance may provide a significant survival advantage for HCC patients.

BACKGROUND Hepatocellular carcinoma (HCC) with vascular invasion at advanced stage is not indicated for surgical options. Conversion therapy is used for unresectable HCC to downstage. Chemotherapy can be more precisely targeted to HCC by using hepatic artery infusion. Bevacizumab and sintilimab are available systemic therapies for HCC. This report describes a 50-year-old man with advanced HCC associated with multiple venous tumor thromboses treated with hepatic artery infusion chemotherapy (HAIC) combined with bevacizumab and sintilimab conversion therapy. CASE REPORT A 50-year-old man was admitted to the hospital due to elevated alpha-fetoprotein (AFP) level in July 2022. Abdominal computed tomography angiography (CTA) revealed a large HCC with multiple venous tumor thromboses. Pulmonary CTA detected arterial embolism and multiple solid nodules. He received HAIC combined with bevacizumab and sintilimab every 3 weeks, and achieved partial response after 3 cycles. However, in March 2023, levels of AFP and protein induced by vitamin K absence-II (PIVKA-II) were re-elevated, showing some pulmonary nodules were enlarged, which was confirmed as pulmonary metastases by positron emission tomography/computed tomography (PET/CT). Subsequently, transarterial chemoembolization (TACE) with bevacizumab and sintilimab was performed, and stereotactic body radiation therapy (SBRT) was used to treat pulmonary metastases. Skull metastasis appeared in March 2024, requiring further local radiotherapy. Despite this, the patient has survived for over 26 months, with a progression-free survival (PFS) of 8 months. CONCLUSIONS HAIC combined with bevacizumab and sintilimab can alleviate primary HCC and tumor thromboses, and further local radiotherapy can control the progression of distant metastases, prolonging the survival time of patients with advanced HCC.

While triplet therapy (HTI), which combines hepatic arterial infusion chemotherapy (HAIC) with tyrosine kinase inhibitors and immune checkpoint inhibitors, is widely used in the treatment of large hepatocellular carcinoma (HCC), there are few reports about its efficacy versus HAIC, and no reliable methods are available for promptly predicting HTI response.

​​Exosomes, as natural intercellular messengers, are gaining prominence as delivery vehicles in nanomedicine, offering a superior alternative to conventional synthetic nanoparticles for cancer therapeutics. Unlike lipid, polymer, or metallic nanoparticles, which often face challenges related to immunogenicity, targeting precision, and off-tumor toxicity, exosomes can effectively encapsulate a diverse range of therapeutic agents while exhibiting low toxicity, favorable pharmacokinetics, and organotropic properties. This review examines recent advancements in exosome bioengineering over the past decade. Innovations such as microfluidics-based platforms, nanoporation, fusogenic hybrids, and genetic engineering have significantly improved loading efficiencies, production scalability, and pharmacokinetics of exosomes. These advancements facilitate tumor-specific cargo delivery, resulting in substantial improvements in retention and efficacy essential for clinical success. Moreover, enhanced biodistribution, targeting, and bioavailability-through strategies such as cell selection, surface modifications, membrane composition alterations, and biomaterial integration-suggests a promising future for exosomes as an ideal nanomedicine delivery platform. We also highlight the translational impact of these strategies through emerging clinical trials. Additionally, we outline a framework for clinical translation that focuses on: cargo selection, organotropic cell sourcing, precision loading methodologies, and route-specific delivery optimization. In summary, this review emphasizes the potential of exosomes to overcome the pharmacokinetic and safety challenges that have long impeded oncology drug development, thus enabling safer and more effective cancer treatments.

For gastric cancer patients, peritoneal metastasis poses a life-threatening risk due to the high incidence of treatment failure and disease recurrence. Conducting additional research aimed at identifying more efficacious strategies is imperative for enhancing treatment outcomes. This study examined the efficacy and safety of systemic chemotherapy plus a PD-1 inhibitor combination with intravenous or intraperitoneal bevacizumab for gastric cancer with peritoneal metastasis.

Peritoneal metastasis (PM) after radical surgery is an important cause of treatment failure in colorectal cancer (CRC). Intraoperative intraperitoneal perfusion chemotherapy may be an effective method for preventing postoperative PM in patients with CRC. This study aimed to explore the safety and feasibility of intraoperatively preventive intraperitoneal perfusion chemotherapy using lobaplatin for CRC.