Up to half of hepatocellular carcinoma(HCC) cases are diagnosed at an advanced stage,for which effective treatment options are lacking,resulting in a poor prognosis. In recent years,the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has demonstrated high efficacy in treating advanced HCC,significantly extending patients' survival,and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy,patients can obtain long-term survival benefits. In order to improve the long-term survival rate of the overall population with liver cancer and achieve the goal of a 15% increase in the overall 5-year survival rate outlined in the "Healthy China 2030" blueprint,the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association,Chinese Society of Liver Cancer,and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts in the field. These discussions focus on the latest progress since the release of Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma(2021 Edition) and have reached new consensus on the modifications and supplements to related key points. This consensus aims to further guide clinical practice,standardize medical behavior,and promote the development of the discipline.

Microspheres are a novel drug delivery system, which provides a new approach for cancer therapy. Anti-cancer agents loaded in microspheres can be released in a controlled and sustained pattern, thereby enhancing the therapeutic efficacy and reducing the side effects and toxicity. The preparation methods for drug delivery microspheres include solvent evaporation, phase separation, spray drying, and microfluidic technology, each of these have advantages and limitations. Based on the preparation materials, drug delivery microspheres can be categorized into natural polymer microspheres, synthetic polymer microspheres and bioceramic microspheres. Natural polymer micro-spheres have good biocompatibility and degradability; synthetic polymer microspheres exhibit superior mechanical properties; bioceramic microspheres have good biocompatibility and specific biological functions, which are widely used in bone tissue engineering. Drug delivery microspheres are used for cancer treatment in various modalities, including photothermal therapy, photodynamic therapy, radioembolization, and immunotherapy, as well as chemotherapy. This article reviews the recent progress of microspheres as nano drug delivery system in cancer treatment to provide a reference for further clinical and translation research.

Objective: To investigate the impact of exosomes and microRNA (miRNA) from placental mesenchymal stem cells on chemotherapy-damaged ovarian granulosa cells. Methods: Various public databases were searched for miRNA targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene. After miRNA transfection into human ovarian granulosa cells, cell growth and expressions of the target miRNA and PTEN were detected. Cisplatin was utilized to induce damage to human ovarian granulosa cells, which were subsequently co-cultured with human placental mesenchymal stem cells and exosomes generated from mesenchymal stem cells, then apoptosis and expressions of PTEN and the target miRNA were detected. Results: After analyzing several databases, miRNA 139-5p (miR-139-5p) was chosen as the target miRNA for this research. Transfection of miR-139-5p mimics into human ovarian granulosa cells elevated miR-139-5p expression level (9 882.080±1 049.130), reduced PTEN protein expression level (0.78±0.11), and increased cell proliferation absorbance (0.85±0.07). Cisplatin treatment severely damaged human ovarian granulosa cells and increased apoptosis, cisplatin-treated cells had a higher apoptosis ratio compared to untreated cells [ (41.9±1.0)% vs (5.0±0.3)%, P<0.001]. In damaged human ovarian granulosa cells, co-cultured with human placental mesenchymal stem cells and exosomes increased miR-139-5p expression levels (1.31±0.04 and 1.20±0.03, respectively) and decreased apoptosis ratios [(20.0±0.4)% and (22.3±1.1)%, respectively]. Conclusion: Placental mesenchymal stem cell-derived exosomes repair damages of cisplatin-induced ovarian granulosa cell and could target PTEN gene through miR-139-5p, which might be a potential option for the treatment of chemotherapy-induced ovarian dysfunction.

The study aims to evaluate the effect of Kaixin Powder(KXP) on the behavior and brain tissue of chemotherapy-treated mice to explore its mechanism in alleviating chemotherapy-induced cognitive impairment in tumor-bearing mice. Thirty female BALB/c mice were inoculated with 4T1 breast cancer cells to establish a tumor-bearing mouse model and randomly divided into the tumor group, a doxorubicin group, and a KXP group. Behavioral tests, including open field test, elevated plus maze test, forced swimming test, tail suspension test, Morris water maze test, and novel object recognition test, were conducted. Pathological examinations, including hematoxylin-eosin staining, Nissl staining, toluidine blue staining, Fluoro-Jade B staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay, immunofluorescence staining, and transmission electron microscopy, were performed. Network pharmacology and whole transcriptome sequencing methods were used to analyze the mechanism of chemotherapy-induced cognitive impairment and the targets of KXP. The results showed that KXP prevented chemotherapy-induced behavioral changes(P&lt;0.001), increased the total movement distance and central zone residence time in the open field test, increased exploration time in the open arm area in the elevated plus maze test, reduced immobility time in the forced swimming test and tail suspension test, reduced escape latency in the Morris water maze test and increased platform crossings, and improved cognitive index in the novel object recognition test. KXP also inhibited chemotherapy-induced neuroinflammation, apoptosis, and autophagy in the prefrontal cortex, and reshaped the RNA expression profile of the prefrontal cortex tissue during chemotherapy(P&lt;0.05). In conclusion, KXP may alleviate chemotherapy-induced cognitive impairment in tumor-bearing mice by reshaping the RNA expression profile of prefrontal cortex tissue, thereby reducing neuronal tissue damage.

The preparation processes of iron-based organic framework(FeMOF) MIL-100(Fe) and MIL-101(Fe) with two different ligands were optimized and screened, and the optimized FeMOF was loaded with piperlongumine(PL) to enhance the biocompatibility and antitumor efficacy of PL. The MIL-100(Fe) and MIL-101(Fe) were prepared by solvent thermal method using the optimized reaction solvent. With particle size, polymer dispersity index(PDI), and yield as indexes, the optimal preparation processes of the two were obtained by using the definitive screening design(DSD) experiment and establishing a mathematical model, combined with the Derringer expectation function. After characterization, the best FeMOF was selected to load PL by solvent diffusion method, and the process of loading PL was optimized by a single factor combined with an orthogonal experiment. The CCK-8 method was used to preliminarily evaluate the biological safety of blank FeMOF and the antitumor effect of the drug-loaded nano preparations. The experimental results showed that the optimal preparation process of MIL-100(Fe) was as follows: temperature at 127.8 ℃, reaction time of 14.796 h, total solvent volume of 11.157 mL, and feed ratio of 1.365. The particle size of obtained MIL-100(Fe) nanoparticles was(108.84±2.79)nm; PDI was 0.100±0.023, and yield was 36.93%±0.79%. The optimal preparation process of MIL-101(Fe) was as follows: temperature at 128.1 ℃, reaction time of 6 h, total solvent volume of 10.005 mL, and feed ratio of 0.500. The particle size of obtained MIL-101(Fe) nanoparticles was(254.04±22.03)nm; PDI was 0.289±0.052, and yield was 44.95%±0.45%. The optimal loading process of MIL-100(Fe) loaded with PL was as follows: the feed ratio of MIL-100(Fe) to PL was 1∶2; the concentration of PL solution was 7 mg·mL~(-1), and the ratio of DMF to water was 1∶5. The drug loading capacity of obtained MIL-100(Fe)/PL nanoparticles was 68.86%±1.82%; MIL-100(Fe) was nontoxic to HepG2 cells at a dose of 0-120 μg·mL~(-1), and the half-inhibitory concentration(IC_(50)) of free PL for 24 h treatment of HepG2 cells was 1.542 μg·mL~(-1). The IC_(50) value of MIL-100(Fe)/PL was 1.092 μg·mL~(-1)(measured by PL). In this study, the optimal synthesis process of MIL-100(Fe) and MIL-101(Fe) was optimized by innovatively using the DSD to construct a mathematical model combined with the Derringer expectation function. The optimized preparation process of MIL-100(Fe) nanoparticles and the PL loading process were stable and feasible. The size and shape of MIL-100(Fe) particles were uniform, and the crystal shape was good, with a high drug loading capacity, which could significantly enhance the antitumor effect of PL. This study provides a new method for the optimization of the nano preparation process and lays a foundation for the further development and research of antitumor nano preparations of PL.

This study aims to explore the effect and mechanism of a mitochondrion-targeted derivative of ergosterol peroxide(Mito-EP) on breast cancer. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of MDA-MB-231 cells treated with different concentrations(0, 0.075, 0.15, 0.3, 0.6, 1.2, and 2.4 μmol·L~(-1)) of Mito-EP. Cells were grouped for treatment with water(blank control), low, medium, and high concentrations(0.15, 0.3, and 0.6 μmol·L~(-1)) of Mito-EP, and ergosterol peroxide(EP)(0.6 μmol·L~(-1)). After the cells were treated for 48 h, flow cytometry was employed to examine the apoptosis rate, reactive oxygen species(ROS) level, mitochondrial membrane potential, and cell cycle distribution, and the apoptosis, ROS, and mitochondrial membrane potential were observed by laser confocal microscopy. A mouse model bearing subcutaneous xenograft tumor was established by injecting 4T1 cell suspension and used to study the inhibitory effect of Mito-EP on breast cancer. Western blot was employed to determine the protein levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), cleaved caspase-7, and cleaved caspase-9 in cells and the tumor tissue. The results showed that Mito-EP reduced the proliferation rate of MDA-MB-231 cells in a concentration-dependent manner. Compared with the blank control group, EP(0.6 μmol·L~(-1)) caused slight changes in the apoptosis rate, ROS level, and mitochondrial membrane potential. However, Mito-EP increased the apoptosis rate, elevated the ROS level, decreased mitochondrial membrane potential, up-regulated the protein levels of Bax, Cyt C, cleaved caspase-7, and cleaved caspase-9, and down-regulated the protein level of Bcl-2(all P&lt;0.05). Moreover, Mito-EP reduced the tumor volume and weight. In summary, Mito-EP may promote apoptosis in breast cancer cells by activating the mitochondrial apoptosis pathway.

In recent years, the treatment of malignant tumors has continually advanced, significantly extending the survival period of cancer patients. Tumors are increasingly present as chronic diseases over the long term, and the cardiovascular toxicity associated with cancer treatment has become increasingly prominent, severely affecting the effective treatment and survival of cancer patients. As a result, cardio-oncology has gained considerable attention as an emerging discipline. However, cardiovascular diseases in cancer patients often have an insidious onset, and early identification and treatment are frequently overlooked. Throughout the course of cancer treatment, it is crucial to reasonably apply cardiac biomarkers for risk stratification, early identification, and screening of cardiovascular diseases in patients, as well as to improve the early diagnosis and treatment levels of cardiovascular diseases in cancer patients. To this end, Cardio-Oncology Group, Chinese Society of Cardiology in conjunction with Cardiovascular Expert Committee, China Medical Doctor Association of Laboratory Medicine, organized experts in relevant fields to compile this consensus. It aims to provide a basis for clinicians to standardize the screening and management of cardiovascular toxicity related to cancer treatment through the reasonable application of cardiac biomarkers.

Neovascular retinal diseases pose a significant burden, often resulting in visual impairment. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs serves as the primary therapeutic approach. Nonetheless, certain patients necessitate continued anti-VEGF treatment post-vitrectomy or other ocular surgeries. Emerging evidence suggests that variations in surgical techniques and postoperative vitreous cavity management may induce distinct intraocular pharmacokinetics (PK) of anti-VEGF agents following vitrectomy, prompting potential adjustments in therapeutic strategies. This review offers a thorough examination of the pharmacokinetic determinants impacting anti-VEGF drugs and their intraocular dynamics post-vitrectomy.

To investigate the effect of dihydroartemisinin (DHA) for enhancing the inhibitory effect of cisplatin (DDP) on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism.

Objective To investigate the mechanism of the basement membrane proteoglycan lumican (LUM) in cisplatin resistance in ovarian cancer and to preliminarily explore its effect on type 1 T helper (Th1) cell differentiation. Methods Differentially expressed genes (DEGs) between cisplatin-resistant and cisplatin-sensitive ovarian cancer cell lines were screened using the public gene expression database (GEO). The expression levels of these genes were detected by RT-qPCR. LUM expression in human ovarian cancer cells was knocked down using small interfering RNA (siRNA), and the knockdown efficiency was verified by Western blotting. Flow cytometry was used to detect the effects of LUM knockdown on the cell cycle and apoptosis of cisplatin-treated ovarian cancer cell lines. Potential target proteins of LUM were screened through the PPI network, and their interactions were validated by molecular docking. The TIMER database was used to screen the effects of LUM on cytokine secretion in ovarian cancer cell lines, and the results were validated by ELISA and RT-qPCR. Flow cytometry was performed to analyze the regulatory effect of LUM on the differentiation of CD4+ T cells. Results GEO data showed that LUM was significantly upregulated in cisplatin-resistant cell lines, and its expression level was correlated with patient prognosis. LUM expression level was higher in that of cisplatin-resistant ovarian cancer cell lines, and cisplatin treatment promoted LUM expression. Knockdown of LUM increased cisplatin-induced apoptosis and cell cycle arrest in ovarian cancer cells, enhancing drug sensitivity. Target gene screening suggested that LUM might regulate cisplatin sensitivity in ovarian cancer cells through interaction with Src homology region phosphatase 2(SHP2). Additionally, TIMER database analysis suggested that high LUM expression inhibited Th1 cell differentiation. Knockdown of LUM in cisplatin-resistant cell lines promoted Th1 cell differentiation by regulating the secretion of interferon γ(IFN-γ) and interleukin 12(IL-12) cytokines, thereby influencing the tumoricidal activity of immune cells. Conclusion LUM is upregulated in cisplatin-resistant ovarian cancer cells and reduces cisplatin sensitivity in ovarian cancer cells by regulating the SHP2-related signaling pathway. LUM also promotes tumor resistance by inhibiting Th1 cell differentiation through the regulation of cytokine secretion by ovarian cancer cells, making it a potential target for ovarian cancer treatment.

Acute myeloid leukemia (AML), one of the most common types of leukemia, is characterized by its high malignancy and rapid progression with a 5-year survival rate of less than 30%. The incidence and mortality rates of AML are increasing with age. Over the past few decades, progress in AML treatment has been relatively slow. While traditional approaches such as chemotherapy and hematopoietic stem cell transplantation have significant limitations including treatment toxicity and chemotherapy resistance, recent advancements in the in-depth study of AML mechanisms have made targeted therapy a new option for AML treatment. Metabolic reprogramming is one of the key features of cancer, and mitochondrial dysfunction has been widely studied in various cancers. Mitochondrial dysfunction is prevalent in AML cells and closely associated with the development of AML. The AML cells exhibit significant differences from normal hematopoietic cells in energy metabolism, autophagy, apoptosis, and other aspects. Given that mitochondria are at the core of cellular energy metabolism, inhibiting pathways related to mitochondrial function holds significant potential for AML treatment. This review aims to explore recent advances on the role of mitochondrial dysfunction in AML cell survival, potential therapeutic targets in mitochondria, and related targeted drugs, aiming to provide ideas for the development of targeted therapies for AML.

With the rapid development of traditional Chinese medicine and the continuous discovery of various anticancer effects of salidroside (sal), it is known that sal inhibits tumor proliferation, invasion and migration by inducing apoptosis and autophagy, regulating the cell cycle, modulating the tumor microenvironment, and controlling cancer-related signaling pathways and molecules. The microRNA (miRNA)-mRNA signaling axis can regulate the expression of target mRNAs by altering miRNA expression, thereby affecting the growth cycle, proliferation, and metabolism of cancer cells. Studies have shown that sal can influence the occurrence and progression of various malignant tumors through the miRNA-mRNA signaling axis, inhibiting the progression of lung cancer, gastric cancer, and nasopharyngeal carcinoma, with a notable time and dose dependence in its antitumor effects. Summarizing the specific mechanism of sal regulating miRNA-mRNA signaling axis to inhibit tumors in recent years can provide a new theoretical basis, diagnosis, and therapeutic methods for the research on prevention and treatment of tumors.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia (AML) in recent years, chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients. Here, we demonstrated the antileukemia activity of a novel small molecular compound NL101, which is formed through the modification on bendamustine with a suberanilohydroxamic acid (SAHA) radical. NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells. It induces DNA damage and caspase 3-mediated apoptosis. A genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) library screen revealed that phosphatase and tensin homologous (PTEN) gene is critical for the regulation of cell survival upon NL101 treatment. The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome (MDS) cells, accompanied by the activation of protein kinase B (AKT) signaling pathway. The inhibition of mammalian target of rapamycin (mTOR) by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death. These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

Chronic myelogenous leukemia (CML) is a hematological malignancy originating from the pluripotent hematopoietic stem cells. Imatinib is the first generation of small molecule tyrosine kinase inhibitors (TKI) that revolutionized the treatment of CML. Flumatinib, as a novel oral TKI that independently developed in China, which can be used as a preferred treatment for CML. Basic researches suggested that the inhibitory effect of flumatinib on CML cell lines is stronger than imatinib. Flumatinib demonstrated that it has better efficacy than imatinib on CML in clinical trials and in real world studies. Flumatinib also showed a higher potency against CML with specific mutations, Ph(+) acute lymphoblastic leukemia and some solid tumors. The adverse events are manageable and tolerable.

With the extensive application of targeted drugs, the survival rate of cancer patients has been significantly improved. However, adverse reactions to the drugs have also become apparent, especially those affecting the ocular surface, which can severely impact patients' vision and quality of life. The article systematically analyzes a variety of targeted drugs, including epidermal growth factor receptor inhibitors, human epidermal growth factor receptor 2 inhibitors, fibroblast growth factor receptor inhibitors, selective estrogen receptor modulators, vascular endothelial growth factor receptor inhibitors, aromatase inhibitors, proteasome inhibitors, antibody-drug conjugates, Bruton's tyrosine kinase inhibitors, FMS-like tyrosine kinase 3 inhibitors, and cyclin-dependent kinase inhibitors, and discusses their adverse reactions on the ocular surface. The review emphasizes the role of clinicians in monitoring and managing patients' ocular surface health and the importance of early diagnosis and intervention to ensure that patients receive optimal visual protection while undergoing antitumor treatment.

In recent years, precision medicine has demonstrated wide applications in cancer therapy, and the focus of precision medicine lies in accurately predicting the responses of different patients to drug treatment. We propose a model for predicting cancer drug sensitivity based on genomic feature distribution alignment and drug structure information. This model initially aligns the genomic features from cell lines with those from patients and removes noise from gene expression data. Subsequently, it integrates drug structure features and employs multi-task learning to predict the drug sensitivity of patients. The experimental results on the genomics of drug sensitivity in cancer (GDSC) dataset indicates that this method achieved a reduced mean square error of 0.905 2, an increased correlation coefficient of 0.875 4, and an enhanced accuracy rate of 0.836 0 which significantly outperformed the recently published methods. On the cancer genome atlas (TCGA) dataset, this method demonstrates an improved average recall rate of 0.571 4 and an increased F1-score of 0.658 0 in predicting drug sensitivity, exhibiting excellent generalization performance. The result demonstrates the potential of this method to assist in the selection of clinical treatment plans in the future.

Renal pelvic carcinoma is a common upper urothelial cancer. The lack of an ideal in vitro model seriously hinders the research progress in the treatment for this disease. This study established a pipeline for the culture of renal pelvic carcinoma organoids based on the tumor tissue samples derived from the patients and tested the organoids to chemotherapeutic drugs. The results of immunohistochemistry and fluorescence experiments confirmed that the renal pelvic carcinoma organoids obtained from culture presented obvious nuclear heteromorphism, which was consistent with the tissue samples from renal pelvic carcinoma patients. The tumor marker molecule CD44 and the cell proliferation marker molecule Ki67 were positive in the organoids, indicating that the organoids were enriched with tumor stem cells and had strong proliferative ability. The renal pelvic carcinoma organoids were highly sensitive to pirarubicin, which had obvious killing effects. In brief, this study successfully established an in vitro model of renal pelvic cancer organoids and tested the sensitivity of the model to chemotherapeutic drugs. The results provide a new laboratory model for the individualized diagnosis and treatment of epithelial carcinomas represented by renal pelvic carcinoma.