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Abstract Cancer and cardiovascular diseases are leading causes of death worldwide. Among them, breast cancer is one of the most common malignancies in women, while atrial fibrillation is one of the most extensively studied arrhythmias, with significant public health implications. As the global population ages and advancements in cancer treatments continue, the survival rates of breast cancer patients have significantly improved, leading to an increasing coexistence of breast cancer and atrial fibrillation. However, the mechanisms underlying this coexistence remain insufficiently studied, and there is no consensus on the optimal treatment strategies for these patients. This review consolidates existing research to systematically explore the epidemiological characteristics, risk factors, and pathophysiological mechanisms of both breast cancer and atrial fibrillation. It focuses on the unique signaling pathways associated with different molecular subtypes of breast cancer and their potential impact on the mechanisms of atrial fibrillation. Additionally, the relationship between atrial fibrillation treatment medications and breast cancer is discussed. These insights not only provide essential evidence for the precise prevention and management of atrial fibrillation in breast cancer patients but also lay a solid theoretical foundation for interdisciplinary clinical management practices.

While drug therapy plays a crucial role in cancer treatment, many anticancer drugs, particularly cytotoxic and molecular-targeted drugs, cause severe side effects, which often limit the dosage of these drugs. Efforts have been made to alleviate these side effects by developing derivatives, analogues, and liposome formulations of existing anticancer drugs and by combining anticancer drugs with substances that reduce side effects. However, these approaches have not been sufficiently effective in reducing side effects. Molecular hydrogen (H2) has shown promise in this regard. It directly reduces reactive oxygen species, which have very strong oxidative capacity, and indirectly exerts antioxidant, anti-inflammatory, and anti-apoptotic effects by regulating gene expression. Its clinical application in various diseases has been expanded worldwide. Although H2 has been reported to reduce the side effects of anticancer drugs in animal studies and clinical trials, the underlying molecular mechanisms remain unclear. Our comprehensive literature review revealed that H2 protects against tissue injuries induced by cisplatin, oxaliplatin, doxorubicin, bleomycin, and gefitinib. The underlying mechanisms involve reductions in oxidative stress and inflammation. H2 itself exhibits anticancer activity. Therefore, the combination of H2 and anticancer drugs has the potential to reduce the side effects of anticancer drugs and enhance their anticancer activities. This is an exciting prospect for future cancer treatments. [ABSTRACT FROM AUTHOR]

Peptidergic systems show promise as targets for fighting tumors. While some peptides encourage the growth and spread of tumor cells and angiogenic mechanisms, others display antitumor properties. As such, peptide ligands and receptor antagonists could be used as antitumor agents alone or in conjunction with chemotherapy or radiotherapy. Peptide receptor antagonists can counteract the oncogenic effects of specific peptides by inducing apoptosis in various types of tumor cells, hindering cancer cell migration and inhibiting angiogenesis. Peptides and peptide receptor antagonists are not currently used in clinical practice as antitumor agents. Still, aprepitant, a neurokinin 1 receptor antagonist, is a promising candidate due to its ability to promote apoptosis in many cancer cells. However, to utilize aprepitant as an anticancer agent, the dosage must be increased and administered for a more extended period. Moving beyond current protocols for aprepitant’s use as an antiemetic is essential. Additionally, a common anticancer strategy with aprepitant is possible regardless of cancer cell type. Finally, combining aprepitant with chemotherapy or radiotherapy is encouraged.

Definition: Peptidergic systems show promise as targets for fighting tumors. While some peptides encourage the growth and spread of tumor cells and angiogenic mechanisms, others display antitumor properties. As such, peptide ligands and receptor antagonists could be used as antitumor agents alone or in conjunction with chemotherapy or radiotherapy. Peptide receptor antagonists can counteract the oncogenic effects of specific peptides by inducing apoptosis in various types of tumor cells, hindering cancer cell migration and inhibiting angiogenesis. Peptides and peptide receptor antagonists are not currently used in clinical practice as antitumor agents. Still, aprepitant, a neurokinin 1 receptor antagonist, is a promising candidate due to its ability to promote apoptosis in many cancer cells. However, to utilize aprepitant as an anticancer agent, the dosage must be increased and administered for a more extended period. Moving beyond current protocols for aprepitant's use as an antiemetic is essential. Additionally, a common anticancer strategy with aprepitant is possible regardless of cancer cell type. Finally, combining aprepitant with chemotherapy or radiotherapy is encouraged. [ABSTRACT FROM AUTHOR]

In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, 4b and 4c showed the most prominent inhibitory effects. The half maximal inhibitory concentration (IC50) values of 4b were 4.42 ± 0.24 μM (NCI-H1299), 3.94 ± 0.01 μM (A549) and 1.56 ± 0.06 μM (NCI-1437). The IC50 values of 4c were 4.60 ± 0.18 µM (NCI-H1299), 4.00 ± 0.08 μM (A549) and 3.51 ± 0.05 μM (NCI-H1437). Furthermore, our results showed that 4b and 4c could effectively inhibit proliferation, colony formation and cell migration in a concentration-dependent manner, as well as induce apoptosis in H1299 cells. In addition, 4b and 4c exerted its anti-tumor effects by inducing cell apoptosis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP and downregulating the protein levels of Bcl-2. Based on these results, it is suggested that 4b and 4c be developed as potential new drugs for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Cell cycle-dependent kinase 2 (CDK2) is located downstream of CDK4/6 in the cell cycle and regulates cell entry into S-phase by binding to Cyclin E and hyper-phosphorylating Rb. Proto-oncogene murine double minute 2 (MDM2) is a key negative regulator of p53, which is highly expressed in tumors and plays an important role in tumorigenesis and progression. In this study, we identified a dual inhibitor of CDK2 and MDM2, III-13, which had good selectivity for inhibiting CDK2 activity and significantly reduced MDM2 expression. In vitro results showed that III-13 inhibited proliferation of a wide range of tumor cells, regardless of whether Cyclin E1 (CCNE1) was overexpressed or not. The results of in vivo experiments showed that III-13 significantly inhibited proliferation of tumor cells and did not affect body weight of mice. The results of the druggability evaluation showed that III-13 was characterized by low bioavailability and poor membrane permeability when orally administered, suggesting the necessity of further structural modifications. Therefore, this study provided a lead compound for antitumor drugs, especially those against CCNE1-amplified tumor proliferation. [ABSTRACT FROM AUTHOR]

While drug therapy plays a crucial role in cancer treatment, many anticancer drugs, particularly cytotoxic and molecular-targeted drugs, cause severe side effects, which often limit the dosage of these drugs. Efforts have been made to alleviate these side effects by developing derivatives, analogues, and liposome formulations of existing anticancer drugs and by combining anticancer drugs with substances that reduce side effects. However, these approaches have not been sufficiently effective in reducing side effects. Molecular hydrogen (H2) has shown promise in this regard. It directly reduces reactive oxygen species, which have very strong oxidative capacity, and indirectly exerts antioxidant, anti-inflammatory, and anti-apoptotic effects by regulating gene expression. Its clinical application in various diseases has been expanded worldwide. Although H2 has been reported to reduce the side effects of anticancer drugs in animal studies and clinical trials, the underlying molecular mechanisms remain unclear. Our comprehensive literature review revealed that H2 protects against tissue injuries induced by cisplatin, oxaliplatin, doxorubicin, bleomycin, and gefitinib. The underlying mechanisms involve reductions in oxidative stress and inflammation. H2 itself exhibits anticancer activity. Therefore, the combination of H2 and anticancer drugs has the potential to reduce the side effects of anticancer drugs and enhance their anticancer activities. This is an exciting prospect for future cancer treatments.

Cabozantinib malate (CBZM), a new anticancer medication, has been studied for its solubility and thermodynamic properties in a variety of {dimethyl sulfoxide (DMSO) + water (H2O)} mixtures at 298.2–318.2 K and 101.1 kPa. Using the shake flask technique, the solubility of CBZM was assessed and the results were correlated to the van't Hoff, Apelblat, Buchowski–Ksiazczak λh, Yalkowsky–Roseman, Jouyban–Acree, and Jouyban–Acree-van't Hoff models. There was a significant correlation between the experimental CBZM solubility data and all computational models, as evidenced by the error values for all computational models being less than 5.0%. Temperature and DMSO mass percentage improved the CBZM mole fraction solubility in the cosolvent solutions of {DMSO + H2O}. At 318.2 K, pure DMSO had the highest mole fraction solubility of CBZM (4.38 × 10−2), whereas pure H2O had the lowest mole fraction solubility (2.24 × 10−7 at 298.2 K). The positive values of computed thermodynamic parameters indicated that the dissolution of CBZM was endothermic and entropy-driven in all of the {DMSO + H2O} solutions investigated. It was found that the CBZM solvation in {DMSO + H2O} solutions is governed by enthalpy. When compared to CBZM-H2O, CBZM-DMSO showed the highest molecular interactions. The findings of this investigation demonstrated that DMSO has a great deal of potential for CBZM solubilization in H2O. [ABSTRACT FROM AUTHOR]

The DNA origami method has revolutionized the field of DNA nanotechnology since its introduction. These nanostructures, with their customizable shape and size, addressability, nontoxicity, and capacity to carry bioactive molecules, are promising vehicles for therapeutic delivery. Different approaches have been developed for manipulating and folding DNA origami, resulting in compact lattice-based and wireframe designs. Platinum-based complexes, such as cisplatin and phenanthriplatin, have gained attention for their potential in cancer and antiviral treatments. Phenanthriplatin, in particular, has shown significant antitumor properties by binding to DNA at a single site and inhibiting transcription. The present work aims to study wireframe DNA origami nanostructures as possible carriers for platinum compounds in cancer therapy, employing both cisplatin and phenanthriplatin as model compounds. This research explores the assembly, platinum loading capacity, stability, and modulation of cytotoxicity in cancer cell lines. The findings indicate that nanomolar quantities of the ball-like origami nanostructure, obtained in the presence of phenanthriplatin and therefore loaded with that specific drug, reduced cell viability in MCF-7 (cisplatin-resistant breast adenocarcinoma cell line) to 33%, while being ineffective on the other tested cancer cell lines. The overall results provide valuable insights into using wireframe DNA origami as a highly stable possible carrier of Pt species for very long time-release purposes. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is an emerging type of regulated cell death and associated with antitumoral therapy, while some microRNAs have been shown to regulate the tumorigenesis and cancer progression. Meanwhile, polyphyllin I (PPI) has exhibited antitumoral effects by promoting cancer cell apoptosis and ferroptosis. However, it is unclear whether PPI induces cancer cell ferroptosis by regulating microRNAs. Methods: We used two gastric cancer cell lines (AGS and MKN-45) to set up a tumor model of the nude mice, which were then treated daily with PPI to measure the cancer growth in vitro and in vivo. Ferroptosis was measured using immunofluorescence staining and flow cytometric analysis according to levels of intracellular ROS, lipid ROS and ferrous ions. Moreover, NRF2 expression was measured by Western blotting. In some experiments, the mimics or inhibitors of miR-124-3p were used to further confirm its involvement in PPI-induced cancer cell ferroptosis. Results: Here we found that miR-124-3p mediated cancer ferroptosis and tumor repression induced by PPI since PPI increased miR-124-3p expression in gastric cancer cells and promoted their ferroptosis, whereas inhibition of miR-124-3p mostly abolished the effects of PPI on tumor growth, ferroptosis and NRF2 expression. Moreover, miR-124-3p mimics promoted cancer cell ferroptosis by downregulating NRF2 through directly targeting 3′-UTR region of NRF2, confirming a role for miR-124-3p in regulating PPI-induced ferroptosis. Conclusion: PPI exerts its antitumoral effects on the gastric cancer by promoting cell ferroptosis via regulating miR-124-3p. Our findings have clinical implications for cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Traditional chemotherapy drugs have definite antitumor mechanisms and good therapeutic efficacy; however, their poor water solubility, serious side effects and drug resistance limit their clinical application. To the best of our knowledge, the present study reported for the first time the in vivo and in vitro anticancer effects of procyanidin B1 (PCB1), a compound that is isolated from natural sources such as grape seeds, apples, peanut skin and cranberries. Cell Counting Kit-8 assay showed that PCB1 effectively decreased the number of viable HCT-116 cells compared with cells treated with the small molecule cytotoxic drug doxorubicin. Quantitative PCR and apoptosis analysis, Cell cycle analysis, and WB analysis) of the molecular mechanism showed that PCB1 induced cell apoptosis and cell cycle arrest in S phase by increasing expression of pro-apoptosis protein caspase-3 and BAX and decreasing expression of anti-apoptosis protein Bcl-2. The efficient antitumor activity of PCB1 was demonstrated through in vivo experiments on a xenograft mouse model, demonstrating that PCB1 significantly suppressed tumor growth. The present study suggested that PCB1 represents a novel class of plant-based compounds isolated from natural sources that can be applied as an anticancer drug. [ABSTRACT FROM AUTHOR]

Context Lung cancer, the most common type of cancer, has a high mortality rate. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae plants, has antitumor effects. Objective We investigated the role of CuB on lung cancer and its potential mechanisms. Materials and methods A549 cells were treated with 0.1, 0.3, 0.6, and 0.9 μM CuB for 12, 24, and 48 h or untreated. Gene and protein levels were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Enzyme-linked immunosorbent assay (ELISA) detected inflammatory factors levels (TNF-α and IL-10). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and colony formation assays measured cell viability, apoptosis, and proliferation. The interaction between miR-let-7c and long non-coding RNA X inactive-specific transcript (XIST) or interleukin-6 (IL-6) was verified by dual-luciferase reporter assays. Results CuB treatment inhibited the proliferation of lung cancer cells and promoted cell apoptosis, and increased the expression of Bax and cleaved caspase3, decreased cyclin B1 and Bcl-2 expression. CuB suppressed XIST and IL-6 expression, and enhanced miR-let-7c expression. XIST silencing enhanced the inhibitory effect of CuB on cell proliferation and the promotion effect on apoptosis via upregulating miR-let-7c. Moreover, XIST targeted miR-let-7c to activate the IL-6/STAT axis. MiR-let-7c overexpression enhanced the regulatory effect of CuB on proliferation and apoptosis via suppressing the IL-6/STAT3 pathway. Discussion and conclusion CuB regulated cell proliferation and apoptosis by inhibiting the XIST/miR-let-7c/IL-6/STAT3 axis in lung cancer. These findings indicate CuB may have the possibility of clinical application in lung cancer treatment.

Metal-organic frameworks (MOFs) are mixed porous materials which are composed of metal clusters or ions and organic pillars. Given their channel tunability, high porosity, large specific surface area, and good biocompatibility, MOFs can be combined with various biological macromolecules. In recent years, they have been widely studied in the field of biomedicine, especially in the loading of anti-tumor drugs, showing great application prospects. Multifunctional anti-tumor MOF combined with different therapeutic methods provides a new idea and method for tumor treatment. On the basis of the structure of MOF, this paper introduces the advantages of using MOF to load anti-tumor drugs and reviews the application of MOF in tumor therapy.

Abnormal angiogenesis plays a key role in cancer progression. In recent years, anti-angiogenic therapy has attracted increasing attention. Berberine (BBR), the main component extracted from Coptis (Ranunculaceae) rhizome, has an anti-angiogenic effect. However, the underlying mechanisms remain to be elucidated. Endothelial cell proliferation is a pivotal process in angiogenesis. In our research, we observed that BBR specifically downregulated the expression of the extracellular signal-regulated kinase 1/2 (ERK1/2) protein in human umbilical vein endothelial cells (HUVECs). The role of BBR in HUVEC proliferation was then assessed using methylthiazolyldiphenyl-tetrazolium bromide and cell counting Kit-8 (CCK-8) assays. The effect of BBR on the ERK1/2 signaling pathway was evaluated using Western blotting. BBR decreased HUVEC proliferation in a dose-dependent manner and inhibited the expression of phospho-ERK1/2 in HUVECs. PD98059, a specific inhibitor of ERK1/2 signaling, attenuated the BBR-induced decrease in the proliferation of HUVECs. Phorbol 12-myristate 13-acetate, a natural activator of ERK1/2 signaling, did not alter BBR-induced proliferation. In conclusion, BBR inhibited endothelial cell proliferation by suppressing ERK1/2 signaling. These findings may provide a potential therapeutic strategy for suppressing tumor growth. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP) is a potent antitumor drug used in first-line chemotherapy against several solid tumors, including breast cancer. However, toxicities and drug resistance limit its clinical application. Thermosensitive liposome (TSL) functionalized with hyaluronic acid (HA) containing cisplatin (TSL-CDDP-HA) was developed by our research group aiming to promote the release of CDDP in the tumor region under hyperthermia conditions, as well as to decrease toxicity. Thus, this study aimed to evaluate this new formulation (HA-coated TSL-CDDP) concerning in vitro behavior and in vivo toxicity compared to non-coated TSL-CDDP and free CDDP. Cytotoxicity assays and nuclear morphology were carried out against triple-negative breast cancer cells (MDA-MB-231), while an in vivo toxicity study was performed using healthy Swiss mice. The results showed an increase (around 3-fold) in cytotoxicity of the cationic formulation (non-coated TSL-CDDP) compared to free CDDP. On the other hand, TSL-CDDP treatment induced the appearance of 2.5-fold more senescent cells with alteration of nuclear morphology than the free drug after hyperthermia condition. Furthermore, the association of liposomal formulations treatment with hyperthermia increased the percentage of apoptotic cells compared to those without heating. The percentage of apoptotic cells was 1.7-fold higher for TSL-CDDP-HA than for TSL-CDDP. For the in vivo toxicity data, the TSL-CDDP treatment was also toxic to healthy cells, inducing nephrotoxicity with a significant increase in urea levels compared to the saline control group (73.1 ± 2.4 vs. 49.2 ± 2.8 mg/mL). On the other hand, the HA-coated TSL-CDDP eliminated the damages related to the use of CDDP since the animals did not show changes in hematological and biochemical examinations and histological analyses. Thus, data suggest that this new formulation is a potential candidate for the intravenous therapy of solid tumors. [ABSTRACT FROM AUTHOR]

Although the clinical application of nanoparticles is still limited by biological barriers and distribution, with the deepening of our understanding of nanoparticles over the past decades, people are gradually breaking through the previous limitations in the diagnosis and treatment of tumors, providing novel strategies for clinical decision makers. The transition of nanoparticles from passive targeting to active tumor-targeting by abundant surface-modified nanoparticles is also a development process of precision cancer treatment. Different particles can be used as targeted delivery tools of antitumor drugs. The mechanism of gold nanoparticles inducing apoptosis and cycle arrest of tumor cells has been discovered. Moreover, the unique photothermal effect of gold nanoparticles may be widely used in tumor therapy in the future, with less side effects on surrounding tissues. Lipid-based nanoparticles are expected to overcome the blood–brain barrier due to their special characteristics, while polymer-based nanoparticles show better biocompatibility and lower toxicity. In this paper, we discuss the development of nanoparticles in tumor therapy and the challenges that need to be addressed. [ABSTRACT FROM AUTHOR]

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Ferroptosis is a form of non-apoptotic and iron-dependent cell death originally identified in cancer cells. Recently, emerging evidence showed that ferroptosis-targeting therapy could be a novel promising anti-tumour treatment. However, systematic analyses of ferroptosis-related genes for the prognosis of non-small cell lung cancer (NSCLC) and the development of antitumor drugs exploiting the ferroptosis process remain rare. This study aimed to identify genes related to ferroptosis and NSCLC and to initially screen lead compounds that induce ferroptosis in tumor cells. We downloaded mRNA expression profiles and NSCLC clinical data from The Cancer Genome Atlas database to explore the prognostic role of ferroptosis-related genes. Four prognosis-associated ferroptosis-related genes were screened using univariate Cox regression analysis and the lasso Cox regression analysis, which could divide patients with NSCLC into high- and low-risk groups. Then, based on differentially expressed risk- and ferroptosis-related genes, the negatively correlated lead compound flufenamic acid (FFA) was screened through the Connective Map database. This project confirmed that FFA induced ferroptosis in A549 cells and inhibited growth and migration in a dose-dependent manner through CCK-8, scratch, and immunofluorescence assays. In conclusion, targeting ferroptosis might be a therapeutic alternative for NSCLC.

Abstract Background CD47 is a widely expressed transmembrane protein located on the surface of somatic cells. It mediates a variety of cellular processes including apoptosis, proliferation, adhesion, and migration. An important role for CD47 is the transmission of a “Don't eat me” signal by interacting with SIRPα on the macrophage surface membrane, thereby preventing the phagocytosis of normal cells. However, cancer cells can take advantage of this autogenous signal to protect themselves from phagocytosis, thus enabling immune escape. Blocking the interaction between CD47 and SIRPα has proven to be effective in removing cancer cells. The treatment of various cancers with CD47 monoclonal antibodies has also been validated. Methods We designed and synthesized a peptide (RS17), which can specifically bind to CD47 and block CD47‐SIRPα signaling. The affinity of RS17 for CD47‐expressing tumor cells was determined, while the inhibition of CD47‐SIRPα signaling was evaluated in vitro and in vivo. Results The results indicated that RS17 significantly promotes the phagocytosis of tumor cells by macrophages and had a similar therapeutic effect compared with a positive control (CD47 monoclonal antibodies). In addition, a cancer xenograft mouse model was established using CD47‐expressing HepG2 cells to evaluate the effect of RS17 on tumor growth in vivo. Using ex vivo and in vivo mouse models, RS17 demonstrated a high inhibitory effect on tumor growth. Conclusions Based on our results, RS17 may represent a novel therapeutic peptide for cancer therapy.

Imatinib mesilate is a well-known antitumor target inhibitor of protein tyrosine kinase, which is effective in different cancer types expressing Bcr / Abl and, in particular, in hemoblastosis. A higher interest to imatinib during the COVID-19 epidemic is explained by the fact that cancer patients are one of the COVID-19 risk groups. Moreover, imatinib target mechanism of action, which is effective in cancer, can have a high potential against the most severe COVID-19 complication such as the disease associated pulmonary fibrosis. COVID-19 associated interstitial pulmonary fibrosis develops as an autoimmune process caused by systemic inflammation with atypical (idiopathic) pneumonia resulting from acute respiratory distress syndrome with the tyrosine kinase mechanism of signaling pathway activation and cellular response. Experi-mental and clinical results showing antifibrotic and dose-related antithrombotic imatinib effect demonstrate perspective use of this antitumor agent to correct COVID-19 associated pneumonia causing a high death rate of patients with COVID-19.The review presents literature data of 2001–2020 discussing pathologic genetic and clinical characteristics of the fibrosis which exacerbates COVID-19 pneumonia in adults. The sequence of the disease processes demonstrates that disease progression with the decreasing oxygen saturation in the peripheral blood intensifies local thrombosis in the lungs. As a result, hypoxia is developing, which is difficult to control and can cause lethal outcome in severe cases. Yet, the conventional antifibrotic and thrombolytic agents can only partially control the process of pneumofibrosis including that of cancer patients. The approximate antifibrotic dose of imatinib 400 mg / day is therapeutic for oncopatho-logy. The antitumor drug registered in many countries and well described side effects and contraindications needs no long-term registration studies for a new indication, therefore, it may be easily prepared for clinical testing.

Background: Genetic instability leads to genome mutations, changes in nucleotide sequences, rearrangements, and gains or losses of part of the chromosomes. This instability can initiate and develop cancer. This study evaluated genomic stability in methotrexate and anthocyanin-treated mammary adenocarcinoma model. Seventy albino mice were divided into seven groups: negative control, anthocyanin, methotrexate, Ehrlich's solid tumor; Ehrlich's solid tumor and methotrexate; Ehrlich's solid tumor and anthocyanin; and Ehrlich's solid tumor, methotrexate, and anthocyanin groups. Results: Tumor weight and size were evaluated. Serum arylesterase activity was low in all the induced tumors and those treated with anthocyanin, methotrexate, or both. Poly[adenosine diphosphate (ADP)-ribose] polymerase activity was high, and glutathione S-transferase activity was low in the tumors treated with anthocyanin, methotrexate, or both, compared with that of the untreated tumor. There was an increase in DNA damage in the mice with solid tumors and those injected with methotrexate or methotrexate and anthocyanin, compared with that in the untreated mice. Conclusions: There was a decrease in genetic instability and DNA damage in the tumor-bearing mice treated with anthocyanin, with a concomitant increase in nuclear poly[adenosine diphosphate (ADP)-ribose] polymerase activity, compared with those of the untreated group. Anthocyanin exerted positive effects in the treatment of mammary adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: During the past decades, increasing attention has been given to elucidating the molecular details of interactions between the pharmacological agents and nucleic acids since the drug–DNA complexation may lead to impairment of DNA replication, strand breaking and mutations. A variety of techniques have been developed to characterize the drug-nucleic acid binding, among which the fluorescence dye displacement assay is one of the most informative approaches. Recently, it was demonstrated that cyanine dyes can be successfully employed for the high throughput screening of the interactions between nucleic acids and drugs. To the best of our knowledge, so far, the potential application of cyanine dyes for the drug-displacement studies remains insufficiently evaluated. Objectives: The aim of the present study was to investigate the ability of a novel cyanine dye to serve as a competitor for the potential antitumor compounds, lanthanide complexes bearing europium (III) tris-β-diketonate (EC) for the DNA and RNA binding sites. Materials and methods: Calf thymus DNA, yeast RNA, trimethine cyanine dye and lanthanide complexes bearing europium (III) tris-β-diketonate were used for sample preparation. The fluorescence data were acquired using Perkin-Elmer LS-55 spectrofluorimeter. Results: Using the fluorescence spectroscopy technique we conducted the displacement reaction trimethine cyanine dye/europium coordination complexes in the presence of double stranded DNA and single-stranded RNA. An increase of the EC concentration in the systems AK3-5/DNA or AK3-5/RNA was followed by a gradual reduction in the AK3-5 fluorescence intensity, indicating that europium (III) tris-β-diketonate compounds can serve as competitors for the trimethine cyanine dye on the nucleic acids. Both the drug chemical structure and the type of nucleic acid proved to control the extent of EC-induced decrease of AK3-5 fluorescence in the presence of the DNA or RNA. Conclusion: By recruiting the potential antitumor agents europium chelate complexes as the competitive ligands for the cyanine dye for the DNA and RNA binding sites, we found that a novel trimethine compound can be effectively used in the fluorescence drug displacement assays.

In recent years, with the development of nanomaterials, the research of drug delivery systems has become a new field of cancer therapy. Compared with conventional antitumor drugs, drug delivery systems such as drug nanoparticles (NPs) are expected to have more advantages in antineoplastic effects, including easy preparation, high efficiency, low toxicity, especially active tumor-targeting ability. Drug delivery systems are usually composed of delivery carriers, antitumor drugs, and even target molecules. At present, there are few comprehensive reports on a summary of drug delivery systems applied for tumor therapy. This review introduces the preparation, characteristics, and applications of several common delivery carriers and expounds the antitumor mechanism of different antitumor drugs in delivery carriers in detail which provides a more theoretical basis for clinical application of personalized cancer nanomedicine in the future.

In recent years, with the development of nanomaterials, the research of drug delivery systems has become a new field of cancer therapy. Compared with conventional antitumor drugs, drug delivery systems such as drug nanoparticles (NPs) are expected to have more advantages in antineoplastic effects, including easy preparation, high efficiency, low toxicity, especially active tumor-targeting ability. Drug delivery systems are usually composed of delivery carriers, antitumor drugs, and even target molecules. At present, there are few comprehensive reports on a summary of drug delivery systems applied for tumor therapy. This review introduces the preparation, characteristics, and applications of several common delivery carriers and expounds the antitumor mechanism of different antitumor drugs in delivery carriers in detail which provides a more theoretical basis for clinical application of personalized cancer nanomedicine in the future. [ABSTRACT FROM AUTHOR]

The aim was to assess the possibility of optimizing the costs of drugs for cancer patients in a subject of the Russian Federation considering the expiration of patent protection period.Materials and methods. The possibility of optimizing the costs of antitumor drugs was studied using a model of a hypothetical region with a population of 2 million. A gradual replacement of the reference drugs with expiring patent protection by generics or biosimilars over 5 years was simulated. Two replacement scenarios were analyzed: 1) maintaining the drug consumption at a stable level; 2) increasing the drug consumption to the level identified in a previous retrospective analysis of the pharmaceutical market. The baseline scenario implied that the drug purchases remained unchanged (in physical and monetary terms) at the level of 2018. We calculated the difference between the drug costs in the baseline scenario and the costs of the same drugs replaced with generics or biosimilars for a 5 year period.Results. By gradually replacing the reference drugs with generics or biosimilars in a region with a population of 2 million and keeping the costs of drugs for solid tumors at the 352.2 million rubles for 5 years (baseline scenario), 69.4 million rubles can be saved. That amount represents 19.7% of the base level if the drug consumption remains at the 2018 level. With an increase in the INN consumption after the release of generics/ biosimilars, no saving is expected; on the contrary, expenses will increase by 14.1% to 400 million rubles, although, an 8.45-fold increase in consumption is projected.Conclusion. With the appearance of generics / biosimilars for the treatment of solid malignant tumors, the possibility of fund saving depends on the increase in drug consumption.

مقدمه: سامانه‌های دارورسانی حاوی داروهای ضد سرطان، مزایای بسیاری در رهایش دارو نسبت به داروهای خوراکی یا تزریقی در درمان سرطان دارند. بنابراین، ساخت سامانه‌هایی برای تحویل کنترل شده‌ی داروهای ضد سرطان در سال‌های اخیر، توجه زیادی را به خود جلب کرده است. روش‌ها: در این تحقیق، نانوذرات کیتوزان (Chitosan-based nanoparticles یا CsNPs) به روش ژل شدن یونی تهیه شد و به عنوان حامل داروی دوکسوروبیسین (Doxorubicin یا DOX) مورد استفاده قرار گرفت. نانوذرات کیتوزان، قبل و بعد از بارگذاری دارو با استفاده از روش‌های میکروسکوپ الکترونی روبشی (Scanning electron microscope یا SEM)، پراکندگي نور پويا (Dynamic light scattering یا DLS) و پتانسیل زتا مورد ارزیابی قرار گرفتند. یافته‌ها: نتایج آزمون‌های برون‌تن (In vitro) انجام شده بر روی این سیستم از نظر میزان رهایش دارو نشان داد نمونه‌ی ساخته شده گزینه‌ی بسیار مناسبی به عنوان حامل داروی ضد سرطان DOX است؛ چرا که با رهایش کنترل شده‌ی دارو در بازه‌ی زمانی (از 120-0 ساعت) به صورت رهایش آهسته و پیوسته، می‌تواند در مقابله با سلول‌های سرطانی مؤثرتر عمل کند. نتیجه‌گیری: بر اساس یافته‌های این مطالعه، استفاده از سامانه‌ی دارورسانی CsNPs/DOX می‌تواند جایگزین ممتازی به جای استفاده از دزهای متعدد تزریق دوکسوروبیسین برای درمان سرطان سینه باشد و محدودیت‌های مربوط به استفاده از این دارو به شیوه‌ی شیمی‌درمانی را مرتفع نماید.

The present study was undertaken to assess the applicability of the novel trimethine cyanine dye AK3-5 as a competitive ligand for the antitumor agents, Eu(III) coordination complexes (EC), in the DNA-containing systems, using the displacement assay as an analytical instrument. The analysis of fluorescence spectra revealed a strong association of AK3-5 with nucleic acids, with the strength of interaction being higher for the double stranded DNA, compared to the single-stranded RNA. The binding parameters of the cyanine dye have been determined in terms of the McGhee & von Hippel neighbouring site-exclusion model and a classical Langmuir model. The AK3-5 association constant in the presence of DNA was found to be equal to 5.1×104 M-1, which is consistent to those of the well-known DNA intercalators. In turn, the binding of the cyanine to the RNA was characterized by a significantly lower association constant ( ~ 3.4×103 M-1) indicating either the external or “partially intercalated” binding mode. The addition of the europium complexes to the AK3-5-DNA system was followed by the fluorescence intensity decrease, with a magnitude of this effect being dependent on the EC structure. The observed fluorescence decrease of AK3-5 in the presence of europium complexes V7 and V9 points to the competition between the cyanine dye and antitumor drugs for the DNA binding sites. The dependencies of the AK3-5-DNA fluorescence intensity decrease vs. europium complex concentration were analyzed in terms of the Langmuir adsorption model, giving the values of the drug association constant equal to 5.4×104 M-1and 3.9×105 M-1 for the europium complexes V7 and V9, respectively. A more pronounced decrease of the AK3-5 fluorescence in the presence of V5 and V10 was interpreted in terms of the drug-induced quenching of the dye fluorescence, accompanying the competition between AK3-5 and Eu(III) complexes for the DNA binding sites. Cumulatively, the results presented here strongly suggest that AK3-5 can be effectively used in the nucleic acid studies and in the dye-drug displacement assays.

Abstract Background Recombinant human calcineurin B subunit (rhCNB) has been shown to be an immune‐stimulatory protein promoting cytokine production and inducing phenotypic maturation of Dendritic cells (DCs). In vivo, it has good antitumor efficacy, and has potential as an antitumor drug. Exogenous rhCNB was found to be internalized into tumor cells via the Toll‐like receptor 4 (TLR4) complex, but it was not known whether its immuno‐modulatory and antitumor functions involved entry by this same route. Methods The production and secretion of the cytokines and chemokines in innate immune cells induced by rhCNB were determined by ELISA, and the expression of CD40, CD80, CD86, and MHCII was analyzed by FACs. Experimental Lewis lung cancer (LLC) model was prepared in C57 BL/6 wild‐type (WT) mice, TLR4−/− mice or their littermates by the inoculation of LLCs in their right armpit, and then administrated daily intraperitoneal injections (0.2 mL) of normal saline, rhCNB 20 mg/kg, and rhCNB 40 mg/kg, respectively. Results Recombinant human calcineurin B subunit promoted the production of antitumor cytokines by innate immune cells, and culture supernatants of rhCNB‐stimulated immune cells induced apoptosis of LLCs. In addition, rhCNB up‐regulated CD40, CD80, CD86, and MHCII expression in macrophages and DCs in TLR4+ cells but failed to do so in TLR4 deficient cells. rhCNB also induced the formation of CD4+ and CD8+T cells in splenocytes from WT mice, but not from TLR4‐deficient littermates. Intraperitoneal administration of WT C57BL/6 mice with rhCNB resulted in a 50% reduction in LLC tumor growth, but failed to inhibit tumor growth in TLR4−/− littermates. Conclusions The in vivo antitumor and immunomodulatory effects of rhCNB are mediated by the TLR4. This conclusion is important for the further understanding and development of rhCNB as an antitumor drug.

Chemotherapy is one of the important means of tumor therapy. However, most of the anti-tumor drugs that currently used in clinic are hydrophobic non-specific drugs, which seriously affect the efficacy of drugs. With the development of nanotechnology, drug efficacy can be improved by selecting appropriate biodegradable nanocarriers for achieving the controlled release, targeting and higher bioavailability of drugs. This paper reviewed the research progress of anti-tumor drug nanoparticle carriers, which mainly summarized the materials used for anti-tumor drug nanoparticle carriers and their effects in anti-tumor drugs, as well as the targeted drug delivery methods of anti-tumor drugs based on nanocarriers.

Chemotherapy is one of the important means of tumor therapy. However, most of the anti-tumor drugs that currently used in clinic are hydrophobic non-specific drugs, which seriously affect the efficacy of drugs. With the development of nanotechnology, drug efficacy can be improved by selecting appropriate biodegradable nanocarriers for achieving the controlled release, targeting and higher bioavailability of drugs. This paper reviewed the research progress of anti-tumor drug nanoparticle carriers, which mainly summarized the materials used for anti-tumor drug nanoparticle carriers and their effects in anti-tumor drugs, as well as the targeted drug delivery methods of anti-tumor drugs based on nanocarriers. [ABSTRACT FROM AUTHOR]

Tissue‐clearing technology is an emerging imaging technique currently utilized not only in neuroscience research but also in cancer research. In our previous reports, tissue‐clearing methods were used for the detection of metastatic tumors. Here, we showed that the cell cycles of primary and metastatic tumors were visualized by tissue‐clearing methods using a reporter system. First, we established cancer cell lines stably expressing fluorescent ubiquitination‐based cell cycle indicator (Fucci) reporter with widely used cancer cell lines A549 and 4T1. Fluorescence patterns of the Fucci reporter were investigated in various tumor inoculation models in mice. Interestingly, fluorescence patterns of the Fucci reporter of tumor colonies were different between various organs, and even among colonies in the same organs. The effects of antitumor drugs were also evaluated using these Fucci reporter cells. Of the three antitumor drugs studied, 5‐fluorouracil treatment on 4T1‐Fucci cells resulted in characteristic fluorescent patterns by the induction of G2/M arrest both in vitro and in vivo. Thus, the combination of a tissue‐clearing method with the Fucci reporter is useful for analyzing the mechanisms of cancer metastasis and drug resistance. [ABSTRACT FROM AUTHOR]

Background: CD47 is a widely expressed transmembrane protein located on the surface of somatic cells. It mediates a variety of cellular processes including apoptosis, proliferation, adhesion, and migration. An important role for CD47 is the transmission of a "Don't eat me" signal by interacting with SIRPα on the macrophage surface membrane, thereby preventing the phagocytosis of normal cells. However, cancer cells can take advantage of this autogenous signal to protect themselves from phagocytosis, thus enabling immune escape. Blocking the interaction between CD47 and SIRPα has proven to be effective in removing cancer cells. The treatment of various cancers with CD47 monoclonal antibodies has also been validated. Methods: We designed and synthesized a peptide (RS17), which can specifically bind to CD47 and block CD47‐SIRPα signaling. The affinity of RS17 for CD47‐expressing tumor cells was determined, while the inhibition of CD47‐SIRPα signaling was evaluated in vitro and in vivo. Results: The results indicated that RS17 significantly promotes the phagocytosis of tumor cells by macrophages and had a similar therapeutic effect compared with a positive control (CD47 monoclonal antibodies). In addition, a cancer xenograft mouse model was established using CD47‐expressing HepG2 cells to evaluate the effect of RS17 on tumor growth in vivo. Using ex vivo and in vivo mouse models, RS17 demonstrated a high inhibitory effect on tumor growth. Conclusions: Based on our results, RS17 may represent a novel therapeutic peptide for cancer therapy. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a highly invasive kind of malignant bone tumor. Exosomes are a type of extracellular vesicles that play an important role in intercellular communication in the microenvironment. Tumor cell progression is promoted through the interaction between exosomes and cells in the microenvironment (including immune cells, mesenchymal cells, and endothelial cells) during tumor development. Neoplastic exosomes can carry a variety of biological information molecules, such as proteins, lipids, and nucleic acids. These molecules play an important clinical role, not only being able domesticate the recipient cells but also being recognized as tumor specific markers. At the same time, exosomes secreted by osteosarcoma can also cooperate with antigen-presenting cells to activate the body's immune response and then to exert anti-tumor effects. Studies on exosomes may be a breakthrough in the search for a new osteosarcoma treatment. In this study, we review the role of neoplastic exosomes in the osteosarcoma microenvironment, summarize their potential as tumor markers, and investigate their clinical application prospects. [ABSTRACT FROM AUTHOR]

• The nanoparticle (CCSP) could increase water solubility of doxorubicin (DOX). • CCSP retained the nature cavity of β-CD and increase the drugs loading content. • DOX@CCSP showed rapid release and high toxicity in tumorous environment. • DOX@CCSP exhibited low drug leakage and negligible toxicity in normal environment. A novel glutathione-responsive (GSH-responsive) star-like amphiphilic polymer (C 12 H 25) 14 -β-CD-(S-S-mPEG) 7 (denoted as CCSP) was designed for efficient antitumor drug delivery. The amphiphilic β-cyclodextrin (β-CD) self-polymerize in water to form a sphere with a diameter of 40–50 nm. The secondary hydroxyl groups of β-CD were modified by dodecyl to form a hydrophobic core and the primary hydroxyl groups of β-CD were decorated with PEG through disulfide bond to form a hydrophilic shell. Since the hydrophobic cavity of β-CD was maintained, the hydrophobic core formed by dodecyl as well as cavity of β-CD provided CCSP with a loading content as high as 39.6 wt%. Importantly, DOX@CCSP exhibited low drug leakage and negligible cytotoxicity in non-reductive physiological environment, while it showed rapid release and high cytotoxicity in reductive tumorous environment via the breakage of disulfide bond. In view of the above-mentioned advantages of DOX@CCSP nanocarriers such as high loading content, proper size, favorable stimulus-response release performance and low leakage, it is believed that CCSP may offer great potential to be used as an intelligent nanocarrier for anticancer drug delivery. [ABSTRACT FROM AUTHOR]

Background: Recombinant human calcineurin B subunit (rhCNB) has been shown to be an immune‐stimulatory protein promoting cytokine production and inducing phenotypic maturation of Dendritic cells (DCs). In vivo, it has good antitumor efficacy, and has potential as an antitumor drug. Exogenous rhCNB was found to be internalized into tumor cells via the Toll‐like receptor 4 (TLR4) complex, but it was not known whether its immuno‐modulatory and antitumor functions involved entry by this same route. Methods: The production and secretion of the cytokines and chemokines in innate immune cells induced by rhCNB were determined by ELISA, and the expression of CD40, CD80, CD86, and MHCII was analyzed by FACs. Experimental Lewis lung cancer (LLC) model was prepared in C57 BL/6 wild‐type (WT) mice, TLR4−/− mice or their littermates by the inoculation of LLCs in their right armpit, and then administrated daily intraperitoneal injections (0.2 mL) of normal saline, rhCNB 20 mg/kg, and rhCNB 40 mg/kg, respectively. Results: Recombinant human calcineurin B subunit promoted the production of antitumor cytokines by innate immune cells, and culture supernatants of rhCNB‐stimulated immune cells induced apoptosis of LLCs. In addition, rhCNB up‐regulated CD40, CD80, CD86, and MHCII expression in macrophages and DCs in TLR4+ cells but failed to do so in TLR4 deficient cells. rhCNB also induced the formation of CD4+ and CD8+T cells in splenocytes from WT mice, but not from TLR4‐deficient littermates. Intraperitoneal administration of WT C57BL/6 mice with rhCNB resulted in a 50% reduction in LLC tumor growth, but failed to inhibit tumor growth in TLR4−/− littermates. Conclusions: The in vivo antitumor and immunomodulatory effects of rhCNB are mediated by the TLR4. This conclusion is important for the further understanding and development of rhCNB as an antitumor drug. [ABSTRACT FROM AUTHOR]

Developing novel nanoscale carriers for drug delivery is of great significance for improving treatment efficiency and reducing side effects of antitumor drugs. In view of the good biocompatibility and special affinity of porphyrin (PP) molecule to cancer cells, it was used to construct a series of metal-doped M@PP (M = Ca ∼ Zn) materials for the delivery of anticancer drug 5-fluorouracil (5-Fu) in this work. Our results reveal that 5-Fu is tightly adsorbed on M@PP (M = Ca ∼ V, Mn ∼ Co, and Zn) by chemisorption, but is physically adsorbed by M@PP (M = Cr, Ni, and Cu). The calculated electronic properties show that all these 5-Fu@[M@PP] (M = Ca ∼ Zn) complexes have both high stability and solubility. Among these 5-Fu@[M@PP] complexes, the chemical bond formed between 5-Fu and Ti@PP has the strongest covalent characteristic, resulting in the largest adsorption energy of −19.93 kcal/mol for 5-Fu@[Ti@PP]. In particular, 5-Fu@[Ti@PP] has the proper recovery time under the near-infrared light at body temperature, which further suggests that Ti@PP is the best drug carrier for 5-Fu. This study not only reveals the interaction strength and nature between 5-Fu and M@PP, but also confirmed the intriguing potential of Ti@PP as nano-carrier for drug delivery. However, further experimental research should be conducted to verify the conclusion obtained in this work. [Display omitted] • Eleven metal-substituted metalloporphyrins M@PP (M = Ca ∼ Zn) was screened for the 5-Fu delivery. • Ti@PP is proved to be the best carrier for 5-Fu among these studied M@PP (M = Ca ∼ Zn) materials. • The interaction nature between 5-Fu and M@PP was revealed by analyzing different parameters obtained by the DFT calculations. • 5-Fu is strongly adsorbed to the Ti site of Ti@PP via forming strong polar covalent bond. • 5-Fu can be quickly released from Ti@PP under the near-infrared light at body temperature. [ABSTRACT FROM AUTHOR]

Anomalous changes of the cell mesenchymal−epithelial transition factor (c-Met) receptor tyrosine kinase signaling pathway play an important role in the occurrence and development of human cancers, including gastric cancer. In this study, we designed and synthesized a novel peptide (CM 7) targeting the tyrosine kinase receptor c-Met, that can inhibit c-Met-mediated signaling in MKN-45 and U87 cells. Its affinity to human c-Met protein or c-Met-positive cells was determined, which showed specific binding to c-Met with high affinity. Its biological activities against MKN-45 c-Met-positive cells were evaluated in vitro and in vivo. As a result, peptide CM 7 exhibited moderate regulation of c-Met-mediated cell proliferation, migration, invasion, and scattering. The inhibitory effect of peptide CM 7 on tumor growth in vivo was investigated by establishing a xenograft mouse model using MKN-45 cells, and the growth inhibition rate of tumor masses for peptide CM 7 was 62%. Based on our data, CM 7 could be a promising therapeutic peptide for c-Met-dependent cancer patients.

A lot of solid tumors are characterized by uncontrolled signal transduction triggered by receptors related to cellular growth. The targeting of these cell receptors with antitumor drugs is essential to improve chemotherapy efficacy. This can be achieved by conjugation of an active targeting agent to the polymer portion of a colloidal drug delivery system loaded with an antitumor drug. The goal of this minireview is to report and discuss some recent results in epidermal growth factor receptor targeting by the GE11 peptide combined with colloidal drug delivery systems as smart carriers for antitumor drugs. The minireview chapters will focus on explaining and discussing: (i) Epidermal growth factor receptor (EGFR) structures and functions; (ii) GE11 structure and biologic activity; (iii) examples of GE11 conjugation and GE11-conjugated drug delivery systems. The rationale is to contribute in gathering information on the topic of active targeting to tumors. A case study is introduced, involving research on tumor cell targeting by the GE11 peptide combined with polymer nanoparticles. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles, with diameters around 12 nm, were synthesized by coprecipitation method. The magnetic properties indicate a superparamagnetic behavior with a coercive field of 9.7 Oe and a blocking temperature of 118 K. Both aqueous and solid magnetoliposomes containing magnetite nanoparticles have sizes below 150 nm, suitable for biomedical applications. Interaction between both types of magnetoliposomes and models of biological membranes was proven. A new antitumor compound, a diarylurea derivative of thienopyridine, active against breast cancer, was incorporated in both aqueous and solid magnetoliposomes, being mainly located in the lipid membrane. A promising application of these magnetoliposomes in oncology is anticipated, allowing a combined therapeutic approach, using both chemotherapy and magnetic hyperthermia. [ABSTRACT FROM AUTHOR]

The mechanism of action of 2-hydroxyoleic acid (2OHOA), a potent antitumor drug, involves the rapid and specific activation of sphingomyelin synthase (SMS), leading to a 4-fold increase in SM mass in tumor cells. In the present study, we investigated the source of the ceramides required to sustain this dramatic increase in SM. Through radioactive and fluorescent labeling, we demonstrated that sphingolipid metabolism was altered by a 24 h exposure to 2OHOA, and we observed a consistent increase in the number of lysosomes and the presence of unidentified storage materials in treated cells. Mass spectroscopy revealed that different sphingolipid classes accumulated in human glioma U118 cells after exposure to 2OHOA, demonstrating a specific effect on C16-, C20-, and C22-containing sphingolipids. Based on these findings, we propose that the demand for ceramides required to sustain the SMS activation (ca. 200-fold higher than the basal level) profoundly modifies both sphingolipid and phospholipid metabolism. As the treatment is prolonged, tumor cells fail to adequately metabolize sphingolipids, leading to a situation resembling sphingolipidosis, whereby cell viability is compromised.