Narrow therapeutic indices of chemotherapeutic agents necessitate precise dosing to ensure efficacy and minimize nephrotoxicity. Due to the complexity of directly measuring Glomerular filtration rate (GFR), renal dosing is usually based on GFR estimation equations. The Cockcroft-Gault formula remains the most widely used equation in cancer patients, despite the availability of more precise kidney function estimation equations. Therefore, the aim of the study was to assess the agreement between Cr and cystatin-C (CysC) based GFR estimation equations and GFR estimated by Cockcroft-Gault for appropriate chemotherapy dosing in cancer patients undergoing assessment for first-Line chemotherapy at an oncology unit of St. Paul's Hospital Millennium Medical College in Ethiopia.

Vitamin E can exert either a cancer preventive effect or improve the therapeutic efficacy of chemotherapeutic drugs against multiple types of cancer. Ample evidence suggests that the cancer preventive activity of vitamin E is form-dependent; however, it is not clear whether its chemosensitization effect is also influenced by its forms. The objectives of this study were to investigate whether the eight natural forms of vitamin E produced differential sensitization effects on cancer chemotherapeutic drugs and to address whether the chemosensitization effect of vitamin E was associated with its inhibitory effect on programmed cell death ligand 1 (PD-L1) signaling. We carried out a comparative evaluation of the chemosensitization effect of eight vitamin E forms using paclitaxel as a representative therapeutic drug and breast/prostate cancer as the representative types of cancer. Results showed that the sensitization effect of vitamin E on chemotherapeutic drugs was also form-dependent, with δ-tocotrienol (δ-T3) as the most effective one for sensitizing breast and prostate cancer cells to paclitaxel, mechanistically associated with its ability to suppress PD-L1-mediated tumor-promoting signaling. The findings provided novel insights into understanding the sensitization effect of vitamin E and its related mechanisms and support that δ-T3 is the best candidate as an enhancer of taxanes among the eight forms.

IntroductionThe Cancer and Aging Research Group (CARG) model predicts chemotherapy-related toxicities in older patients; however, its applicability has not been validated in Taiwanese patients. This study aims to validate the CARG model in older Taiwanese patients with solid tumors.MethodsPatients (N = 258) aged ≥65 years with solid tumors from a single medical center, slated for first-line chemotherapy, were recruited between 2018 and 2021, with follow-up until December 31, 2022. Patients were categorized into low- (N = 85), medium- (N = 117), and high- (N = 56) risk based on CARG. Validation of CARG involved receiver operating characteristic (ROC) curves. Individual CARG variables were analyzed using univariate analysis for their impact on toxicities and survival.ResultsToxicities of grades ≥3 were 38.8%, 44.4%, and 67.9% (P = .001) in the three ascending risk groups, and there were significant differences in both hematological (P = .002) and non-hematological (P < .001) toxicities. ROC was 0.631 (95% CI: 0.562-0.700), indicating satisfactory discrimination. One-year overall survival rates were 88.7%, 79.7%, and 63.8%, respectively, in ascending-risk groups, with high-risk groups showing decreased survival (P = .002). In the multivariate analysis, decreased hemoglobin, history of falls, and inability to walk one block remained significantly associated with toxicity. For overall survival, the inability to take medications was the only independent predictor.ConclusionThis prognostic study validated the CARG model in a heterogeneous solid tumor cohort in Taiwan. In addition to predicting both hematological and non-hematological toxicities, CARG could offer insights into patient survival among older individuals with cancer.

Hepatocellular carcinoma (HCC) remains a major global health challenge, with limited efficacy of current immunotherapeutic strategies. Immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns (DAMPs), offers a promising approach to enhance antitumor immunity. Arsenic trioxide (ATO), an ICD inducer, may synergize with PD-1 inhibitors to overcome therapeutic resistance, though the underlying mechanisms remain unclear.

Diarrhea is primary adverse effect of capecitabine (Cap) causing treatment discontinuation. The aim of this study was to construct an early-warning model for predicting the Cap-induced diarrhea.

Amaranthus spinosus is a medicinal plant with notable pharmacological properties. In the present work, silver nanoparticles (AgNPs) were synthesized using methanolic leaf extract of A. spinosus. The synthesis of AgNPs was indicated by a color change from green to brown and confirmed through UV-Vis spectroscopy, FTIR, SEM, and XRD analyses. The XRD peaks between 20° and 50° confirmed the crystalline nature of AgNPs, while SEM (1 μm scale) revealed uniformly distributed spherical nanoparticles below 100 nm. The AgNPs exhibited potent antimicrobial activity, with the highest inhibition observed against Klebsiella pneumoniae (20 mm at 100 μg), surpassing the plant extract. Antioxidant assays proved the free radical scavenging capacity of AgNPs compared with standard ascorbic acid. At 500 μg/mL, AgNPs achieved 71% DPPH scavenging, 75% hydroxyl radical scavenging, and 68% reducing power, significantly outperforming the plant extract. The in vitro anticancer property of AgNPs against HT-29 colorectal cancer cells revealed a concentration-dependent cytotoxic effect, with maximum cell death at 100 μg/mL. AO/EtBr staining confirmed apoptosis through a shift from green to orange/red fluorescence, while DAPI staining indicated nuclear condensation and fragmentation. These findings highlight A. spinosus-derived AgNPs as promising candidates for biomedical applications, offering enhanced antimicrobial, antioxidant, and anticancer properties via eco-friendly synthesis.

Dauriporphine is a major ingredient of Manispernum daericum DC., which has been demonstrated to show wide anti-tumor activities. miR-424-5p, as a regulator of lung cancer, was hypothesized to serve as the therapeutic target for dauriporphine This study evaluated the potential of dauriporphine in treating lung adenocarcinoma and revealed the underlying molecular mechanism.

Regarding their distinct physico-chemical and bioactivity characteristics, silver nanoparticles 'AgNPs' are extensively utilized in numerous scientific purposes.

Procyanidins (PCs), dietary polyphenols found in fruits, vegetables, and beverages, exhibit potent anticancer properties. Their mechanisms of action involve modulating oxidative stress, inhibiting angiogenesis, inducing apoptosis, and preventing tumor progression. Despite promising preclinical and clinical findings, their therapeutic potential remains underexplored. This review aims to provide a comprehensive analysis of the anticancer properties of PCs, including their bioavailability, pharmacokinetics, and safety. A systematic literature search was conducted across databases such as PubMed, Scopus, and Web of Science, utilizing Medical Subject Headings (MeSH) terms and specific keywords. Studies were selected based on predefined inclusion criteria, focusing on in vitro, in vivo, and clinical evidence. PCs demonstrate anticancer effects through multiple pathways, including inhibition of pro-inflammatory cytokines, suppression of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways, and regulation of apoptosis-related proteins such as BCL2-associated X protein (BAX), B-cell lymphoma 2 (BCL-2), and caspases. PCs demonstrate anticancer effects through multiple pathways, including inhibition of pro-inflammatory cytokines, suppression of the PI3K/AKT/mTOR and MAPK/ERK pathways, and regulation of apoptosis-related proteins such as BAX, BCL-2, and caspases. However, their low oral bioavailability and metabolic instability pose challenges for clinical application. Current research highlights the need for novel delivery systems, such as nanoparticles and liposomes, to enhance systemic absorption and therapeutic efficacy. Ongoing clinical trials are investigating the potential of PCs as adjuvants in cancer therapy, either alone or in combination with chemotherapeutic agents. Future studies should focus on optimizing their pharmacokinetics, exploring synergistic effects with existing treatments, and conducting large-scale clinical trials to validate their efficacy and safety. PCs hold promise as natural anticancer agents, with the potential to complement conventional therapies and improve patient outcomes.

Angiogenesis plays a critical role in cancer progression, highlighting the need for effective anti-angiogenic therapies. Zerumbone (ZER), a phytochemical compound, is known for its anti-angiogenic and anti-carcinogenic effects in various cancer cell lines. Cisplatin (CIS) is a widely used chemotherapeutic agent that effectively inhibits tumor growth. Combining CIS with anti-angiogenic agents like ZER may enhance the anticancer efficacy of CIS and improve treatment outcomes. This study aimed to evaluate the acute toxicity and anti-angiogenic effects of ZER, CIS, and the ZER + CIS combination in a zebrafish larval model. At higher concentrations, the ZER + CIS combination demonstrated only minimal toxicity. Both CIS and ZER exhibited significant anti-angiogenic activity, as indicated by the depletion of o-dianisidine-positive red blood cells in circulation compared to the control. The combination of ZER and CIS synergistically enhanced the down-regulation of VEGF-A (p < 0.001), VEGFR-2, NRP-1A, and NRP-2B, confirming the synergistic action of the two compounds. In conclusion, the combination of ZER and CIS exhibited superior anti-angiogenic effects compared to either treatment alone, suggesting a promising therapeutic strategy for cancer treatment.

Glioma is a highly aggressive central nervous system tumor with limited treatment options, presenting a significant challenge for effective therapy. Despite advancements, the role of tumor-associated macrophages (TAMs) in glioma remains poorly understood, especially regarding their polarization and its impact on the immune response. This study investigates the effects of Lysosomal-associated protein transmembrane 4 A (LAPTM4A) deficiency on the polarization of TAMs and its role in modulating anti-tumor immunity. Using C57BL/6 male mice, we established an orthotopic glioma model and employed single-cell RNA sequencing, flow cytometry, in vitro co-culture systems, and in vivo anti-PD-1 therapy experiments to explore the functional role of LAPTM4A. We found that LAPTM4A promotes M2 polarization of TAMs, contributing to glioma progression by enhancing cell proliferation and invasion. In contrast, LAPTM4A-deficient glioma models show a shift towards M1 macrophage phenotypes, leading to stronger immune activation and increased sensitivity to anti-PD-1 therapy. These results suggest that targeting LAPTM4A may provide a novel strategy to improve glioma treatment by modulating TAM polarization and enhancing immune responses. This research lays the groundwork for future therapies aimed at reprogramming the tumor microenvironment to combat glioblastoma.

Imatinib treatment is approved for several indications, including chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). Although adverse events are common, hypersensitivity reactions are not. Because there is a clear clinical benefit of imatinib treatment, re-introduction of imatinib after a hypersensitivity reaction should be considered.

A series of aminated quinolinequinones linked to piperazine analogs (QQ1-7) were synthesized and screened against the full panel of National Cancer Institute (NCI) cancer cell lines for their potential as cytotoxic agents. The Developmental Therapeutics Program of the NCI analyzed the NCI-60 screening results and revealed that seven QQs were potent inhibitors of cancer cell growth across several cell lines, advancing them to the five-dose assay. Encouraged by the NCI five-dose assay results, the cytotoxicity of the selected QQs (QQ1 and QQ4) was further studied in three cancer cell lines-HCT-116 (colon cancer), ACHN (renal cancer), MCF7, and T-47D (breast cancer)-as well as in a normal cell line (HUVEC) for a deeper understanding. QQ1 was the hit compound for ACHN cells with an IC50 value of 1.55 μM. QQ1 could inhibit ACHN cell proliferation, induce oxidative stress, and cause cell cycle arrest in ACHN cells. QQ1 did not affect the apoptotic value in ACHN cells. Oral bioavailability was poor for both QQ1 and QQ4 in vivo in rats due to faster intrinsic hepatic clearance in comparison with humans, as evidenced by in vitro metabolic studies with rat and human liver microsomes. Molecular docking simulation with putative target CDC25A revealed the interaction of QQ1 and QQ4 with active site residues responsible for substrate recognition.

Acute myeloid leukemia (AML) is marked by uncontrolled growth of malignant cells in the bone marrow, presenting a major challenge in hematology despite treatment advances. Curcumin, a polyphenol from turmeric, shows promise as an anticancer agent with multiple mechanisms targeting pathways like NF-κB, STAT3, PI3K/AKT, and MAPK. This review highlights curcumin's antileukemic effects, including apoptosis induction, cell proliferation inhibition, and angiogenesis modulation. Although low bioavailability limits its clinical use, nanoformulations such as liposomes and micelles have improved curcumin's stability and uptake. Combining curcumin with standard chemotherapies has shown synergistic effects, enhancing anticancer efficacy. Preclinical studies consistently demonstrate curcumin's antileukemic impact in AML cell lines and animal models, showing reduced tumor load and prolonged survival. Ongoing clinical trials are assessing curcumin's safety and efficacy in AML patients, with early results indicating potential. However, larger randomized trials are needed for confirmation. In conclusion, curcumin's anticancer properties and safety profile make it a valuable candidate for AML treatment. Further research is necessary to refine delivery methods, optimize combination therapies, and substantiate its role through clinical trials.

Tumorigenesis and metastasis of solid tumors are coupled to profound biophysical changes that alter cancer cells' mechanobiology, critically impacting metastatic progression. In particular, cell stiffness determines the ability of cancer cells to invade surrounding tissues, withstand shear fluid stress and evade immune surveillance. Here, we summarize the biological factors, pathological factors, and therapeutic modalities that affect the mechanobiology of cancer cells. We focus on clinically utilized chemotherapeutics and targeted therapies that show direct and indirect modulation of cancer cells' stiffness and discuss how these treatments can be used in combination with other treatment modalities to improve patient outcomes. Finally, we list the outstanding challenges in the field and provide a perspective on expanding the clinical utilization of experimental therapeutics that can act as "mechanotherapeutics" by regulating mechanobiology of cancer cells.

Besides targeting tumor cells via canonical synthetic lethality, poly(ADP-ribose) polymerase inhibitors (PARPis) can remodel tumor immune microenvironment (TIME), which then affects PARPis' anti-tumor capabilities. However, exact function of PARPis on TIME remains insufficiently explored. Here, by leveraging paired samples during neoadjuvant PARPi Niraparib treatment derived from a prospective clinical trial, we discovered that the expression of immune checkpoint ligand B7-H3 was induced by PARPis in cancer-associated fibroblasts (CAFs) of ovarian cancer. Depletion of B7-H3 in CAFs by using host cd276 (coding B7-H3) knockout mice or B7-H3 deficient fibroblast cells both boosted T cell functions and enhanced the anti-tumor capacities of PARPis in immunocompetent mouse models. Besides, increased B7-H3 on CAFs also attenuated the anti-tumor potentials of T cells in co-culture system. Mechanistically, PARPis blocked autophagic flux by inhibiting PIP4K2A expression, a critical regulator of autophagosome and lysosome fusion, and therefore dampening the lysosomal degradation of B7-H3. Importantly, neutralizing B7-H3 antibodies had synergistic effects with PARPis and achieved superior therapeutic efficacy than PARPis plus PD-1 blockade in a syngeneic mouse ovarian cancer model. Collectively, this study revealed an autophagy-mediated pathway by which PARPis contribute to immune evasion via enhanced B7-H3 accumulation on CAFs, highlighting the complexity of the regulation of PARPis on TIME and the potential application of combining PARPis with B7-H3 blockade in the treatment of ovarian cancer.

Thymic epithelial tumors (TETs), categorized predominantly as thymoma (T) or thymic carcinoma (TC), face a challenging prognosis and limited treatment options. Although chemotherapy remains the established treatment for advanced TETs, its responses tend to be short-lived. The emergence of immunotherapy, particularly programmed cell death-1 (PD-1) and programmed death ligand-1 inhibitors (PD-L1), is increasingly being regarded as a promising new treatment option for various malignancies.

As a member of the chaperonin-containing tailless complex polypeptide 1 (TCP1) complex, which plays a pivotal role in ensuring the accurate folding of numerous proteins, chaperonin-containing TCP1 subunit 6A (CCT6A) participates in various physiological and pathological processes. However, its effects on cell death and cancer therapy and the underlying mechanisms need further exploration in colorectal cancer (CRC) cells.

This research extracted and purified polysaccharides from Corydalis yanhusuo residue. The structure of purified polysaccharides of Corydalis yanhusuo (CYP-1) was characterized by methods such as infrared spectroscopy, nuclear magnetic resonance, and monosaccharide composition analysis. In addition, the purified polysaccharides were subjected to preliminary studies in vitro for antioxidant and antitumor activities. The average molecular weight of CYP-1 was 1.427 × 10³ kDa. FT-IR analysis revealed that CYP-1 displayed characteristic absorption bands typical of polysaccharides. Furthermore, NMR spectroscopy suggested that the sugar residue units of CYP-1 consisted of →1)-α-D-Glcp-(4→, →6)-α-D-Galp-(1→, and α-D-Arap-(1→. In vitro bioactivity experiments revealed that CYP-1 exhibits antioxidant activity and effectively inhibits HepG2 cell proliferation with an IC50 value of 1.381 mg/mL, suggesting its potential as a natural antioxidant and antitumor agent.

The Wnt/β-catenin signaling pathway is a highly conserved signaling pathway closely linked to cancer development through various biological processes, including oncogenic transformation, genomic instability, cancer cell proliferation, stemness, metabolism, cell death, immune regulation, and metastasis. Notably, its activation plays a crucial role in drug resistance to chemotherapy, targeted therapy and immunotherapy. Recent advances in drug development have identified several targeted inhibitors acting at key nodal points of this pathway, with some demonstrating synergistic efficacy when combined with immunotherapeutic agents. This review provides a comprehensive analysis of current understanding regarding the Wnt/β-catenin pathway in malignancy, emphasizing its multifaceted roles in tumor initiation, therapeutic resistance, and immune regulation. Additionally, we summarized the clinical performance of combination therapies targeting the Wnt/β-catenin pathway in conjunction with chemotherapy, targeted therapy, and immunotherapy. Although clinical development remains at a relatively early stage, pharmacological modulation of Wnt/β-catenin signaling offers considerable potential as a novel therapeutic paradigm in precision oncology.