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Introduction. Chemotherapeutics are widely recognized for their adverse side-effects during anti-cancer regiments. One of the complementary approaches to circumvent this dilemma could be the exploitation of natural compounds, which could optimally counteract the cellular damages during chemotherapy. The present study ventures to evaluate the natural flavonoid, chrysin (5,7-dihydroxyflavone) for its therapeutic immunomodulatory properties along with the chemotherapeutic drug, cyclophosphamide (CP). Methods. Male Wistar albino rats were utilized for this study. Assays were conducted for acute toxicity, Hemolysis, Phagocytosis, Natural Killer (NK) cell cytotoxicity, and oxidative stress. RT-PCR, ELISA and Western Blot were performed to assess the expression of inflammatory markers. Results. Assay results such as Phagocytosis Index (0.009 ± 0.001), NK cell cytotoxicity (61.10 ± 4.99%), expression of Perforin (0.45 ± 0.05 fold) and Granzyme (0.86 ± 0.01 fold), hepatic antioxidative enzymes GSH (27.75 ± 1.54 μg/mg), SOD (7.10 ± 0.35 U/mg) and CAT (249.06 ± 31.30 μM/min/mg) and splenic hepatic antioxidative enzymes GSH (20.88 ± 0.74 μg/mg), SOD (7.10 ± 0.35 U/mg) and CAT (249.06 ± 31.30 μM/min/mg) among the CP-treated groups were compared with those for the CP+chrysin treated groups which were evaluated to be significantly increased with values of 0.016 ± 0.001, 82.73 ± 2.87%, 0.77 ± 0.08 fold, 1.11 ± 0.02 fold, 47.60 ± 3.02 μg/mg, 08.97 ± 0.42 U/mg, 467.19 ± 15.92 μM/Min/mg, 29.02 ± 1.59 μg/mg, 5.17 ± 0.94 U/mg, 310.29 ± 9.1330 μM/Min/mg, respectively. Histopathological examination indicated that CP+chrysin treated groups could recover from cellular damage triggered during the CP treatment. Conclusion. Results indicate the cytoprotective role of chrysin, which in turn, could be reliably administered as a complementary therapy along with CP during chemotherapy. [ABSTRACT FROM AUTHOR]

Cancer, as a complicated disease, is considered to be one of the major leading causes of death globally. Although various cancer therapeutic strategies have been established, however, some issues confine the efficacies of the treatments. In recent decades researchers for finding efficient therapeutic solutions have extensively focused on the abilities of stem cells in cancer inhibition. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can the most widely extracted from various sources such as the bone marrow (BM), placenta, umbilical cord (UC), menses blood, Wharton's jelly (WJ), adipose tissue and dental pulp (DP). These cells are capable of differentiating into the osteoblasts, chondrocytes, and adipocytes. Due to the unique characteristics of MSCs such as paracrine effects, immunomodulation, tumor-tropism, and migration, they are considered promising candidates for cancer therapeutics. Currently, MSCs are an excellent living carrier for delivery of therapeutic genes and chemical agents to target tumor sites. Also, exosomes, the most important extracellular vesicle released from MSCs, act as a strong cell-free tool for cancer therapeutics. MSCs can prevent cancer progression by inhibiting several signaling pathways, such as wnt/β-catenin and PI3K/AKT/mTOR. However, there are several challenges associated with the use of MSCs and their exosomes in the field of therapy that need to be considered. This review explores the significance of MSCs in cell-based therapy, focusing on their homing properties and immunomodulatory characteristics. It also examines the potential of using MSCs as carriers for delivery of anticancer agents and their role in modulating the signal transduction pathways of cancer cells. [ABSTRACT FROM AUTHOR]

In this study, we aimed to identify the chemotherapeutic potential of Bornetella nitida, a Dasycladacean that contains various phytochemicals. Phytochemical extraction was performed using gradient maceration with nhexane, chloroform, ethyl acetate, and methanol. Additionally, toxicity tests as well as antioxidant activity, cytotoxicity, phytochemical, and molecular docking analyses against three main cervical cancer proteins were performed. The B. nitida extracts showed moderate toxicity with LC50 ranging from 116.06 to 713.12 μg mL− 1 . The free-radical scavenging activity of 2,2-diphenyl-1-picrylhydrazyl varied with solvent polarity, exhibiting IC50 values of 22.20, 87.77, 401.55, and 752.08 μg mL− 1 when extracted using n-hexane, chloroform, ethyl acetate, and methanol, respectively. Meanwhile, the cytotoxicity against HeLa cells ranged from 281.09 to 1329.33 μg mL− 1 , with the highest activity shown by the ethyl acetate extract. Gas chromatography-mass spectrometry (GCMS) analysis revealed the presence of phytochemicals with various bioactivities in the extract, such as L-ascorbic acid 2,6-dihexadecanoate, octadec-9-enoic acid, hexadecatrienoic acid, 2,4-bis(1,1-dimethylethyl)phenol, 9,12- octadecadienoic acid (Z,Z), 1,2-benzenedicarboxylic acid, 2,6,10-trimethyl-14-ethylene-14-pentadecene, and phytol. Docking studies implied that the compounds commonly interact well with the binding site of the target protein. Overall, our results indicate that B. nitida extracts especially ethyl acetate extract can be developed as chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Chemokines are small, secreted cytokines crucial in the regulation of a variety of cell functions. The binding of chemokine C-X-C motif chemokine ligand 12 (CXCL12) (stromal cell-derived factor 1) to a G-protein-coupled receptor C-X-C chemokine receptor type 4 (CXCR4) triggers downstream signaling pathways with effects on cell survival, proliferation, chemotaxis, migration, and gene expression. Intensive and extensive investigations have provided evidence suggesting that the CXCL12-CXCR4 axis plays a pivotal role in tumor development, survival, angiogenesis, metastasis, as well as in creating tumor microenvironment, thus implying that this axis is a potential target for the development of cancer therapies. The structures of CXCL12 and CXCR4 have been resolved with experimental methods such as X-ray crystallography, NMR, or cryo-EM. Therefore, it is possible to apply structure-based computational approaches to discover, design, and modify therapeutic molecules for cancer treatments. Here, we summarize the current understanding of the roles played by the CXCL12-CXCR4 signaling axis in cellular functions linking to cancer progression and metastasis. This review also provides an introduction to protein structures of CXCL12 and CXCR4 and the application of computer simulation and analysis in understanding CXCR4 activation and antagonist binding. Furthermore, examples of strategies and current progress in CXCL12-CXCR4 axis-targeted development of therapeutic anticancer inhibitors are discussed. [ABSTRACT FROM AUTHOR]

This review article explores the mushrooming research on chalcone hybrid molecules as promising anticancer agents. Chalcones, featuring a unique chemical structure, exhibit diverse biological activities, including potent anticancer properties. Various synthetic chalcones and their derivatives have demonstrated remarkable efficacy against different cancer cell lines, offering advantages such as reduced mutagenicity. The article summarizes recent advancements in chalcone hybrid research, highlighting their potential in cancer treatment and paving the way for novel, safer, and more effective chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Abstract Background Resistance can develop during treatment of advanced endometrial cancer (EC), leading to unsatisfactory results. Fanconi anemia complementation group D2 (Fancd2) has been shown to be closely related to drug resistance in cancer cells. Therefore, this study was designed to explore the correlation of Fancd2 with EC resistance and the mechanism of Fancd2. Methods Real-time quantitative PCR (RT-qPCR) was used to detect the expression of Fancd2 in EC tissues and cells. EC cells (Ishikawa) and paclitaxel-resistant EC cells (Ishikawa/TAX) were transfected to knock down Fancd2. In addition, the ferroptosis inhibitor Ferrostatin-1 was adopted to treat Ishikawa/TAX cells. The sensitivity of cancer cells to chemotherapeutic agents was observed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and inhibitory concentration (IC)50 was calculated. Reactive oxygen species (ROS) levels were measured by flow cytometry, the activity of malondialdehyde (MDA) and the levels of glutathione (GSH) and Fe2+ in cells were detected by corresponding kits, and protein expression of solute farrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was obtained through western blot. Results Compared with the normal tissues and endometrial epithelial cells, Fancd2 expression was significantly increased in EC tissues and Ishikawa cells, respectively. After knock-down of Fancd2, Ishikawa cells showed significantly increased sensitivity to chemotherapeutic agents. Besides, compared with Ishikawa cells, the levels of ROS, the activity of MDA, and the levels of GSH and Fe2+ were significantly decreased in Ishikawa/TAX cells, while the expression levels of SLC7A11 and GPX4 were significantly increased. Knock-down of Fancd2 significantly increased the ferroptosis levels in Ishikawa/TAX cells, but this effect could be reversed by Ferrostatin-1. Conclusion Fancd2 increases drug resistance in EC cells by inhibiting the cellular ferroptosis pathway.

Background: Resistance can develop during treatment of advanced endometrial cancer (EC), leading to unsatisfactory results. Fanconi anemia complementation group D2 (Fancd2) has been shown to be closely related to drug resistance in cancer cells. Therefore, this study was designed to explore the correlation of Fancd2 with EC resistance and the mechanism of Fancd2. Methods: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of Fancd2 in EC tissues and cells. EC cells (Ishikawa) and paclitaxel-resistant EC cells (Ishikawa/TAX) were transfected to knock down Fancd2. In addition, the ferroptosis inhibitor Ferrostatin-1 was adopted to treat Ishikawa/TAX cells. The sensitivity of cancer cells to chemotherapeutic agents was observed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and inhibitory concentration (IC)50 was calculated. Reactive oxygen species (ROS) levels were measured by flow cytometry, the activity of malondialdehyde (MDA) and the levels of glutathione (GSH) and Fe2+ in cells were detected by corresponding kits, and protein expression of solute farrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was obtained through western blot. Results: Compared with the normal tissues and endometrial epithelial cells, Fancd2 expression was significantly increased in EC tissues and Ishikawa cells, respectively. After knock-down of Fancd2, Ishikawa cells showed significantly increased sensitivity to chemotherapeutic agents. Besides, compared with Ishikawa cells, the levels of ROS, the activity of MDA, and the levels of GSH and Fe2+ were significantly decreased in Ishikawa/TAX cells, while the expression levels of SLC7A11 and GPX4 were significantly increased. Knock-down of Fancd2 significantly increased the ferroptosis levels in Ishikawa/TAX cells, but this effect could be reversed by Ferrostatin-1. Conclusion: Fancd2 increases drug resistance in EC cells by inhibiting the cellular ferroptosis pathway. [ABSTRACT FROM AUTHOR]

The overall survival of patients with the advanced and recurrent gastric cancer (GC) remains unfavorable. In particular, this is due to cancer spreading and resistance to chemotherapy associated with the epithelial-mesenchymal transition (EMT) of tumor cells. EMT can be identified by the transcriptome profiling of GC for EMT markers. Indeed, analysis of the TCGA and GTEx databases (n = 408) and a cohort of GC patients (n = 43) revealed that expression of the CDH2 gene was significantly decreased in the tumors vs. non-tumor tissues and correlated with the overall survival of GC patients. Expression of the EMT-promoting transcription factors SNAIL and ZEB1 was significantly increased in GC. These data suggest that targeting the EMT might be an attractive therapeutic approach for patients with GC. Previously, we demonstrated a potent anti-cancer activity of the olive leaf extract (OLE). However, its effect on the EMT regulation in GC remained unknown. Here, we showed that OLE efficiently potentiated the inhibitory effect of the chemotherapeutic agents 5-fluorouracil (5-FU) and cisplatin (Cis) on the EMT and their pro-apoptotic activity, as was demonstrated by changes in the expression of the EMT markers (E- and N-cadherins, vimentin, claudin-1) in GC cells treated with the aforementioned chemotherapeutic agents in the presence of OLE. Thus, culturing GC cells with 5-FU + OLE or Cis + OLE attenuated the invasive properties of cancer cells. Importantly, upregulation of expression of the apoptotic markers (PARP cleaved form) and increase in the number of cells undergoing apoptosis (annexin V-positive) were observed for GC cells treated with a combination of OLE and 5-FU or Cis. Collectively, our data illustrate that OLE efficiently interferes with the EMT in GC cells and potentiates the pro-apoptotic activity of certain chemotherapeutic agents used for GC therapy. [ABSTRACT FROM AUTHOR]

Background Chemotherapy-induced nausea and vomiting are commonly experienced side effects in breast cancer (BCa) patients. Antiemetic drugs used in BCa treatment are either inhibitors or inducers of cytochrome P450 (CYP) enzymes, while anticancer drugs are metabolized by CYPs. Objectives The purpose of the present work was to evaluate in silico drug-drug interaction (DDI) potential between BCa chemotherapeutic drugs and antiemetic agents. Methods The Drug-Drug Interaction™ module of GastroPlus™ was employed to assess CYP-related interactions between antiemetic and anticancer therapy combinations. The CYP inhibitory or inducing parameters (IC50, Ki, EC50) used in simulations were obtained from the literature. Results Analyses of twenty-three BCa drugs indicated that 22% of the chemotherapeutic drugs do not need an antiemetic agent due to their low emetogenicity, whereas 30% of the anticancer drugs are not metabolized by CYPs. The remaining eleven anticancer drugs metabolized by CYPs generated ninety-nine combinations with nine antiemetics. Simulation of DDIs suggest that about half of the pairs did not demonstrate any potential for DDI, whereas 30%, 10%, and 9% of the pairs showed weak, moderate, and strong interaction potential, respectively. In the present study, netupitant was the only antiemetic that showed strong inhibitory interactions (predicted AUC ratio > 5) with CYP3A4-metabolzied anticancer therapies (e.g., docetaxel, ribociclib, olaparib). Moderate to no interactions were observed with ondansetron, aprepitant, rolapitant, and dexamethasone in combination with anticancer agents. Conclusion It is critical to recognize that these interactions can get amplified in cancer patients because of the severity of the disease and chemotherapy toxicities. Clinicians need to be aware of the DDI likelihood of the drug combinations used in BCa treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Chemotherapeutic agents are used to control tumor proliferation. However, their influence in the pre-metastatic niche of target organs has not been well studied. Oxaliplatin (OXA) is a drug applied in standard treatments of colorectal cancer (CRC), while the direct effect of which on the pre-metastatic microenvironment of the liver remains unclear. Methods Models of liver metastases were established with luciferase expressing CT26 cells in BALB/c and BALB/c-nude mice. Single-cell RNA Sequencing was performed to examine the immune microenvironment in the liver elicited by OXA. Immunofluorescence and flowcytometry were utilized to confirm the changes in the number of immune cells. LDH, CellTrace CFSE Cell Proliferation and apoptosis assays were conducted to explore the impact of OXA on T cells ex vivo. The correlation between chemotherapy-related lymphopenia and metastases was assessed by meta-analysis. Results Herein we discovered that administration of OXA prior to the occurrence of liver metastasis actually accelerated tumor development and colonization in the liver. Single-cell RNA sequencing revealed that the landscape of the liver immune microenvironment had been changed to immunosuppressive phenotype. Macrophages after the treatment of OXA exhibited a high ability to inhibit the activation of T cells. Further investigation revealed a significant decrease in the number of T cells in the liver, particularly CD8+ T cells with reduced capacity of proliferation, activation, and killing. When mice were treated with T cell supplementation, the OXA-induced metastasis was notably abolished, indicating that the OXA-primed liver microenvironment could be reversed by the infusion of T cells. Consistent with our findings in mice, a meta-analysis was performed to verify that chemotherapy-related lymphopenia was associated with an inferior prognosis related with high incidence of metastasis, suggesting the pivotal role of chemotherapy in pre-metastatic niche formation. Furthermore, a notable reduction in the count of both macrophages and T cells was observed in the liver of colorectal cancer (CRC) patient undergoing OXA-based chemotherapy. Conclusions Our findings proposed that immunosuppressive microenvironment in liver induced by OXA enhanced liver metastasis of colorectal cancer, which highlighted a new consideration to balance the pro metastases and anti-cancer possibility of OXA treatment.

Background: Chemotherapeutic agents are used to control tumor proliferation. However, their influence in the pre-metastatic niche of target organs has not been well studied. Oxaliplatin (OXA) is a drug applied in standard treatments of colorectal cancer (CRC), while the direct effect of which on the pre-metastatic microenvironment of the liver remains unclear. Methods: Models of liver metastases were established with luciferase expressing CT26 cells in BALB/c and BALB/c-nude mice. Single-cell RNA Sequencing was performed to examine the immune microenvironment in the liver elicited by OXA. Immunofluorescence and flowcytometry were utilized to confirm the changes in the number of immune cells. LDH, CellTrace CFSE Cell Proliferation and apoptosis assays were conducted to explore the impact of OXA on T cells ex vivo. The correlation between chemotherapy-related lymphopenia and metastases was assessed by meta-analysis. Results: Herein we discovered that administration of OXA prior to the occurrence of liver metastasis actually accelerated tumor development and colonization in the liver. Single-cell RNA sequencing revealed that the landscape of the liver immune microenvironment had been changed to immunosuppressive phenotype. Macrophages after the treatment of OXA exhibited a high ability to inhibit the activation of T cells. Further investigation revealed a significant decrease in the number of T cells in the liver, particularly CD8+ T cells with reduced capacity of proliferation, activation, and killing. When mice were treated with T cell supplementation, the OXA-induced metastasis was notably abolished, indicating that the OXA-primed liver microenvironment could be reversed by the infusion of T cells. Consistent with our findings in mice, a meta-analysis was performed to verify that chemotherapy-related lymphopenia was associated with an inferior prognosis related with high incidence of metastasis, suggesting the pivotal role of chemotherapy in pre-metastatic niche formation. Furthermore, a notable reduction in the count of both macrophages and T cells was observed in the liver of colorectal cancer (CRC) patient undergoing OXA-based chemotherapy. Conclusions: Our findings proposed that immunosuppressive microenvironment in liver induced by OXA enhanced liver metastasis of colorectal cancer, which highlighted a new consideration to balance the pro metastases and anti-cancer possibility of OXA treatment. [ABSTRACT FROM AUTHOR]

The discovery of alpha-tocopheryl succinate (alpha-TS) as a cancer therapeutic agent markedly stimulated research with or without tumor therapeutic agents on cancer cells and normal cells. Results showed that alpha-TS treatment induced apoptosis in cancer cells and enhanced the apoptotic effects of tumor therapeutic agents on tumor cells in a synergistic manner without affecting the growth of normal cells. Liposomal alpha-TS was more effective than alpha-TS. Some tumors are difficult to treat with chemotherapeutic agents while some become resistant of such treatment. Using a nanotechnology technique, it was demonstrated that alpha-TS conjugated with a chemotherapeutic agent enhanced the levels of apoptosis and restored the sensitivity of tumor cells to that chemotherapeutic agent. The mechanisms of action of alpha-TS alone or in combination with therapeutic agents include the following: (a) inhibition of the expression of oncogenes C-myc and H-ras; (b) alterations in the levels of expression of numerous genes; (c) activation of caspases; (d) inhibition of angiogenesis; (e) destabilization of mitochondria and lysosomes; (f) inhibition of production of production of prostaglandin E2 (PGE2) and PGE2-mediated pro-inflammatory responses; (g) reduction of survivin signaling pathway; and (h) reduction of CD47 expression on the tumor cell surface causing enhancement of phagocytic activity of macrophages leading to engulfment of tumor cells. Despite impressive results in cell culture and in animal models, no studies with alpha-TS alone or in combination with cancer therapeutic agents in human cancer resistant to these therapies have been performed. Alpha-TS inhibited the growth of cancer cells without affecting normal cells. Alpha-TS enhanced the effects of therapeutic agents on tumor cells but not on normal cells. Liposomal alpha-TS was more effective than alpha-TS. Using a nanotechnology technique, alpha-TS conjugated with a chemotherapeutic agent produced synergistic growth inhibition in cancer cells but not in normal cells. [ABSTRACT FROM AUTHOR]

Multiple programmed cell death pathways (pyroptosis, apoptosis, and necroptosis) are closely related to the progression of hepatocellular carcinoma (HCC). Furthermore, molecular interactions among pyroptotic, apoptotic, and necroptotic components may be new targets for cancer therapy. However, the signature of the genes involved in the interaction between pyroptosis, apoptosis, and necroptosis (PANRGs), and their prognostic value, is still unclear in HCC. In this study, we used HCC clinical and expression data from TCGA and GEO to explore the relationship between PANRGs and HCC. First, we determined the copy number variation incidence of 41 PANRGs genes and explored the prognostic correlation of these genes in HCC. Based on PANRGs, two molecular subgroups of HCC associated with prognosis were identified. We also found significant differences in the overall survival time and the immune infiltration of HCC patients between the two subgroups. Finally, based on the nine PANRGs (CDC25B, EZH2, HMOX1, PLK1, SQSTM1, WEE1, TREM2, MYCN, and FLT3), we constructed a prognostic model using LASSO-Cox regression analysis. The prognostic model could predict OS of HCC patients in TCGA and GEO cohorts with high accuracy. Significant correlations were found between prognosis-related PANRGs and the tumor immune microenvironment (TIME), tumor mutational burden (TMB), and drug sensitivity. In conclusion, we explored the role of PANRGs in HCC and the association of these genes with TIME, TMB, and drug sensitivity. [ABSTRACT FROM AUTHOR]

Simple Summary: Improving experimental conditions in preclinical animal studies is essential. Automated digital ventilated cages offer the advantage of continuous monitoring of animal locomotor activity in their home cage over a long period, improving animal welfare through the reduction in animal handling. The potential utility of this technology remains understudied and deserves investigation in the field of oncology. Here, we determined the utility of continuous assessment of locomotor activity using the DVC® technology on the SCID (severe combined immunodeficiency) mouse model treated with reference oncology compounds. Our results showed that the use of the DVC® locomotion index is able to identify significant deleterious effects on animal activity, while suggesting perturbations of animal behaviors that would not have been detected by staff clinical assessment over a limited daytime observation. The use of this technology also helped to detect the anticipated effects of the drugs tested, highlighting the potential of this digital biomarker to differentiate treatment adverse effects in preclinical oncology studies. Background: Improving experimental conditions in preclinical animal research is a major challenge, both scientifically and ethically. Automated digital ventilated cages (DVC®) offer the advantage of continuous monitoring of animal activity in their home-cage. The potential utility of this technology remains understudied and deserves investigation in the field of oncology. Methods: Using the DVC® platform, we sought to determine if the continuous assessment of locomotor activity of mice in their home cages can serve as useful digital readout in the monitoring of animals treated with the reference oncology compounds cisplatin and cyclophosphamide. SCID mice of 14 weeks of age were housed in DVC® cages in groups of four and followed with standard and digital examination before and after treatment over a 17-day total period. Results: DVC® detected statistically significant effects of cisplatin on the activity of mice in the short and long term, as well as trends for cyclophosphamide. The activity differences between the vehicle- and chemotherapy-treated groups were especially marked during the nighttime, a period when animals are most active and staff are generally not available for regular checks. Standard clinical parameters, such as body weight change and clinical assessment during the day, provided additional and complementary information. Conclusion: The DVC® technology enabled the home cage monitoring of mice and non-invasive detection of animal activity disturbances. It can easily be integrated into a multimodal monitoring approach to better capture the different effects of oncology drugs on anti-tumor efficacy, toxicity, and safety and improve translation to clinical studies. [ABSTRACT FROM AUTHOR]

Twenty different infectious disorders induced by bacteria, viruses, and parasites are categorized as neglected tropical diseases (NTDs) by WHO. The severity of chagas disease remains a major concern in endemic areas and an emerging public health hazard in nonendemic countries. Trypanosoma cruzi, the etiological agent of this NTD, is mostly transmitted by triatomine vectors and comprises a range of epidemiologically significant variants. Current chemotherapeutics are obsolete, and one of the primary reasons for treatment cessation is their poor safety and effectiveness. Due to the aforementioned challenges, researchers are now focusing on discovering alternative novel safe, and economically reachable therapies for the treatment of trypanosomiasis. Certain target‐based drugs that target specific biochemical processes of the causative parasites have been described as potential antichagasic agents that possesses various types of heterocyclic scaffolds. These flexible molecules have a wide range of biological actions, and various synthesized compounds with strong activity have been documented. This review aims to discuss the available literature on synthetic anti‐T. cruzi drugs that will give a food for thought to medicinal chemists thriving to design and develop such drugs. Furthermore, some of the studies discussed herein are concerned with the potential of novel drugs to block new viable sites in T. cruzi. [ABSTRACT FROM AUTHOR]

The ketone bodies, sodium and lithium salts of acetoacetate (AcAc) and sodium 3-hydroxybutyrate (3-HB; commonly called beta-hydroxybutyrate) have been found to inhibit the proliferation of cancer cells. Previous studies have suggested that lithium itself may be an inhibiting agent but may be additive or synergistic with the effect of AcAc. We previously found that sodium acetoacetate (NaAcAc) inhibits the growth of human colon cancer cell line SW480. We report here similar results for several other cancer cell lines including ovarian, cervical and breast cancers. We found that NaAcAc does not kill cancer cells but rather blocks their proliferation. Similar inhibition of growth was seen in the effect of lithium ion alone (as LiCl). The effect of LiAcAc appears to be due to the combined effects of acetoacetate and the lithium ion. The ketone bodies, when given together with chemotherapeutic agents, rapamycin, methotrexate and the new peptide anti-cancer agent, PNC-27, substantially lowers their IC50 values for cancer cell, killing suggesting that ketone bodies and ketogenic diets may be powerful adjunct agents in treating human cancers. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is a common childhood sarcoma, and its treatment is hindered by adverse effects, chemoresistance, and recurrence. Interleukin (IL)-6 production by tumors plays a significant role in inflammation, carcinogenesis, and metastasis. This study aimed to investigate the antiproliferative potential of luteolin derivatives in OS and to evaluate interleukin production. MG-63, Saos-2, HOS, and 143B human OS cell lines were incubated with luteolin and eight derivatives containing hydroxy, chlorine, or alkyl substitutions. The cell viability and growth were evaluated in the presence of these compounds. Apoptosis was also examined through the analysis of the Bax expression and caspase-3 activity. Finally, the gossypetin effects were measured regarding the production of proinflammatory cytokines interleukin (IL)-6, IL-1β, and IL-12p70. Our findings show that gossypetin was the most potent compound, with proliferation-suppressing activities that induced a series of critical events, including the inhibition of the cell viability and growth. Apoptosis was associated with enhanced caspase-3 activity and increased Bax expression, indicating the involvement of the intrinsic pathway of apoptosis. Moreover, pre-/co-treatment with gossypetin significantly reduced the autocrine production of proinflammatory cytokines. Further investigation is required; nevertheless, considering the link between inflammation, carcinogenesis, and metastasis in OS, our findings suggest that gossypetin exhibits anti-proliferative and anti-inflammatory properties that are potentially relevant in the clinical context. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) plays a pivotal role in cancer development and progression. In this line, revealing the precise mechanisms of the TME and associated signaling pathways of tumor resistance could pave the road for cancer prevention and efficient treatment. The use of nanomedicine could be a step forward in overcoming the barriers in tumor-targeted therapy. Novel delivery systems benefit from enhanced permeability and retention effect, decreasing tumor resistance, reducing tumor hypoxia, and targeting tumor-associated factors, including immune cells, endothelial cells, and fibroblasts. Emerging evidence also indicates the engagement of multiple dysregulated mediators in the TME, such as matrix metalloproteinase, vascular endothelial growth factor, cytokines/chemokines, Wnt/β-catenin, Notch, Hedgehog, and related inflammatory and apoptotic pathways. Hence, investigating novel multitargeted agents using a novel delivery system could be a promising strategy for regulating TME and drug resistance. In recent years, small molecules from natural sources have shown favorable anticancer responses by targeting TME components. Nanoformulations of natural compounds are promising therapeutic agents in simultaneously targeting multiple dysregulated factors and mediators of TME, reducing tumor resistance mechanisms, overcoming interstitial fluid pressure and pericyte coverage, and involvement of basement membrane. The novel nanoformulations employ a vascular normalization strategy, stromal/matrix normalization, and stress alleviation mechanisms to exert higher efficacy and lower side effects. Accordingly, the nanoformulations of anticancer monoclonal antibodies and conventional chemotherapeutic agents also improved their efficacy and lessened the pharmacokinetic limitations. Additionally, the coadministration of nanoformulations of natural compounds along with conventional chemotherapeutic agents, monoclonal antibodies, and nanomedicine-based radiotherapy exhibits encouraging results. This critical review evaluates the current body of knowledge in targeting TME components by nanoformulation-based delivery systems of natural small molecules, monoclonal antibodies, conventional chemotherapeutic agents, and combination therapies in both preclinical and clinical settings. Current challenges, pitfalls, limitations, and future perspectives are also discussed. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are the cells in a primary tumor that have the opportunity to self-renew as well as differentiate into certain cell types, thus forming a mixed tumor. CSCs have been shown to be involved in every aspect of cancer development, including tumor initiation, proliferation, and metastatic activity; they are also involved in chemotherapeutic drug resistance and the recurrence of certain cancers. Based on these capabilities, CSCs have been explored as the next target for the treatment and management of cancer. Salinomycin (SAL), a polyether ionophore antibiotic being used in the poultry industry, was identified as a powerful anti-cancer compound that possesses broad-spectrum activities, especially against CSCs. Here we point out the noteworthy work reported on SAL’s mechanism of action, anticancer activities, toxicity, and clinic applications. In addition, SAL derivatives synthesized by different research groups and their biological activity will also be highlighted.

Background: Long-term childhood cancer survivors (CCS) are at high risk of having dyslipidemia including low high density lipoprotein cholesterol (HDL-C). However, little is known about the prevalence of low HDL-C and the impact of therapy exposure on HDL composition early after treatment is terminated. Methods: This associative study included 50 children and adolescents who had completed their cancer treatments (< 4 years). Clinical characteristics (demographic, diagnosis, treatment, anthropometric parameters), fasting plasma lipids, apoliporoteins (Apo) A-I and composition of HDL fractions (HDL2 and HDL3) were assessed. Data were stratified according to the presence of dyslipidemia and median doses of therapeutic agents and compared using Fisher exact or Mann–Whitney tests. Univariate binary logistic regression analyses were carried out to evaluate the associations between the clinical and biochemical characteristics and having low HDL-C. Composition of HDL2 and HDL3 particles was assessed in a sub-group of 15 patients and compared to 15 age- and sex-matched healthy controls using Wilcoxon paired test. Results: Of the 50 pediatric cancer patients included in this study (mean age: 11.30 ± 0.72 y; mean time since end of treatment: 1.47 ± 0.12 y; male: 38%), 8 had low HDL-C (16%), all of which were adolescent at diagnosis. Higher doses of doxorubicin were associated with lower HDL-C and Apo A-I levels. In hypertriglyceridemic patients and compared to normolipidemics, triglycerides (TG) content was greater in HDL2 and HDL3 fractions whereas esterified cholesterol (EC) content was lower in HDL2. Enrich TG content of HDL3 and lower EC of HDL2 was found in patients exposed to ≥ 90 mg/m2 doxorubicin. Factors positively associated with the risk of having low HDL-C were age, being overweight or obese and exposure to doxorubicin ≥ 90 mg/m2. Compared to healthy controls, a sub-group of 15 patients showed higher TG and free cholesterol (FC) content of HDL2 and HDL3 and lower EC content in HDL3. Conclusions: Overall, we found abnormalities in HDL-C and Apo A-I levels and in HDL composition early after pediatric cancer treatment that are influenced by age, overweight or obesity status and exposure to doxorubicin. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are the cells in a primary tumor that have the opportunity to self-renew as well as differentiate into certain cell types, thus forming a mixed tumor. CSCs have been shown to be involved in every aspect of cancer development, including tumor initiation, proliferation, and metastatic activity; they are also involved in chemotherapeutic drug resistance and the recurrence of certain cancers. Based on these capabilities, CSCs have been explored as the next target for the treatment and management of cancer. Salinomycin (SAL), a polyether ionophore antibiotic being used in the poultry industry, was identified as a powerful anti-cancer compound that possesses broad-spectrum activities, especially against CSCs. Here we point out the noteworthy work reported on SAL's mechanism of action, anticancer activities, toxicity, and clinic applications. In addition, SAL derivatives synthesized by different research groups and their biological activity will also be highlighted. [ABSTRACT FROM AUTHOR]

Cancer is a complex genetic disorder due to uncontrolled growth of abnormal cells in the body, causes damage to the immune system, and may lead to life-threatening situations. Common approaches to cancer treatment includes chemotherapy, hormone therapy, immunotherapy, radiation therapy etc. Development of novel and natural chemotherapeutic agents is highly demanded because of the side effects of synthetic drugs. Essential oils from aromatic plants exhibited antioxidant, antimutagenic, antiproliferative and immunomodulating activities. Mechanism of multidrug resistance and synergistic action of these volatile constituents are responsible for their chemopreventive properties. These oils primarily comprising of terpenoid constituents and are characterized by volatility, aroma, low molecular weight etc. The chemical composition of these oils varies depending on the environmental condition, species, plant part and geographical region. Literature analysis revealed that plant essential oils play an important role in cancer prevention and treatment. Cancer patients exposed to essential oils via inhaler devices were found to have less anxiety, stress, and nausea and insomnia. Nowadays, there is an increasing demand for investigating the biological properties of aromatic plants due to their availability, chemical diversity, and low toxicity. In aromatherapy, Citrus essential oils repress cancer related pain and enhance immune system. Current review summarizes existing variability of the chemical composition of Citrus essential oils and its molecular level anticancer mechanism against various human cancer cell lines. Citrus essential oils enhance cytotoxicity, antiproliferative and apoptotic behavior of cancer cell lines. Since essential oils exhibiting significant anticancer potential is worthy of further investigation for cancer chemoprevention. The findings of various research activities can be exploited by cancer researchers world wide for the development of anticancer drugs which can relieve cancer symptoms. [ABSTRACT FROM AUTHOR]

Quercetin has a wide range of potential health benefits, working as a direct or indirect agent or an adjuvant following different principles. It may be used as a generally useful or exclusive supplement, but also specifically used to treat an acute or chronic condition. Quercetin may work as a cancer chemopreventive and chemotherapeutic agent, because this versatile substance, which owns antioxidant and anti‐inflammatory properties, may also kill cancer cells and also holds senolytic properties. While both the specific chemo‐preventive or chemotherapeutic uses as a drug need clinical trials, it may be used without any contraindication as a general chemo‐preventive supplement. [ABSTRACT FROM AUTHOR]

Phospholipids have managed to overcome several challenges, which hampered the therapeutic potential of conventional drug delivery systems. As formulation excipients, phospholipids have become progressively essential. This review intends to summarize the basic characteristics and usefulness of phospholipids in oral delivery systems (viz. nanocochleates and drug-phospholipid complex) to overcome problems relating to the solubility and permeability of anti-cancer agents. The first segment of the review will give insight into nanocochleates, which are cylindrical cigar-like structures that have the ability to deliver hydrophobic as well as hydrophilic drugs. In the second section, we have provided an overview of the phospholipid complex formed because of the interaction between drugs and phospholipids. In a nutshell, our review offers two strategies for boosting the use of phospholipids in the oral delivery of anti-cancer agents, which can help overcome the existing problems and open up new avenues and advances in developing oral drug delivery systems. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a frequent chemotherapeutic drug used to treat various malignant tumors. One of the key factors that diminish its therapeutic importance is DOX-induced nephrotoxicity. The first-line oral antidiabetic drug is metformin (Met), which also has antioxidant properties. The purpose of our study was to investigate the underlying molecular mechanisms for the potential protective effects of Met on DOX-triggered nephrotoxicity. Four animal groups were assigned as follows; animals received vehicle (control group), 200 mg/kg Met (Met group), DOX 15 mg/kg DOX (DOX group), and a combination of DOX and Met (DOX/Met group). Our results demonstrated that DOX administration caused marked histological alterations of widespread inflammation and tubular degeneration. Notably, the DOX-induced dramatic up-regulation of the nuclear factor-kappa B/P65 (NF-κB/P65), microtubule-associated protein light chain 3B (LC3B), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-1beta (IL-1β), 8-hydroxy-2′ -deoxyguanosine (8-OHdG), and Beclin-1 in renal tissue. A marked increase in the malondialdehyde (MDA) tissue level and a decrease in the total antioxidant capacity (TAC) were also recorded in DOX-exposed animals. Interestingly, Met could minimize all histopathological changes as well as the disruptions caused by DOX in the aforementioned measures. Thus, Met provided a workable method for suppressing the nephrotoxicity that occurred during the DOX regimen via the deactivation of the Beclin-1/LC3B pathway. [ABSTRACT FROM AUTHOR]

Abstract Research on cancer treatment is always of great importance because of the extensive and difficult treatment options and side effects of chemotherapeutic agents. Due to this, novel techniques for cancer treatment are the need of the day. Nowadays, nanotechnology is of great interest for its applications as diagnostic tools, theragnostic, contrasting agents, and vehicles for delivering drugs. Nanoparticles (NPs) are made up of biocompatible and biodegradable polymers that improve the pharmacokinetic and pharmacodynamic properties of drugs, reduce side effects, improve stability, prolong the release of drug, and reduce the dosing frequency. Poly (lactic-co-glycolic acid) (PLGA) is FDA-approved synthetic polymer which can be used to formulate NPs that can be targeted to a specific site for the safe and effective delivery of drugs. PLGA-based NPs can be used for a variety of cancer therapies including tumor-targeted drug delivery, gene therapy, hyperthermia, and photodynamic therapy. This article discusses the method of preparation, characterization, encapsulation of chemotherapeutic drugs, effect of physicochemical properties of PLGA- based NPs, and how we can exploit these aspects through various methods of preparation for drug loading, biodistribution, target specificity, and their use in cancer treatment. Along with these targeting strategies, gene therapy, cancer immunotherapy, and various applications have also been discussed. This article also aims to discuss the incorporation of diagnostic tools and therapeutic moiety in one versatile formulation of PLGA-NPs and the difficulties faced in translating this promising tool to clinical use.

Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy. [ABSTRACT FROM AUTHOR]

Chemotherapeutic agents such as methotrexate (MTX), raltitrexed (RTX), 5-fluorouracil (5-FU), hydroxyurea (HU), and retinoic acid (RA), and valproic acid (VPA), an antiepileptic drug, all can cause malformations in the developing central nervous system (CNS), such as neural tube defects (NTDs). However, the common pathogenic mechanisms remain unclear. This study aimed to explore the mechanisms of NTDs caused by MTX, RTX, 5-FU, HU, RA, and VPA (MRFHRV), based on network pharmacology and molecular biology experiments. The MRFHRV targets were integrated with disease targets, to find the potential molecules related to MRFHRV-induced NTDs. Protein–protein interaction analysis and molecular docking were performed to analyze these common targets. Utilizing the kyoto encyclopedia of genes and genomes (KEGG) signaling pathways, we analyzed and searched the possible causative pathogenic mechanisms by crucial targets and the signaling pathway. Results showed that MRFHRV induced NTDs through several key targets (including TP53, MAPK1, HSP90AA1, ESR1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN) and multiple signaling pathways such as PI3K/Akt pathway, suggesting that abnormal proliferation and differentiation could be critical pathogenic contributors in NTDs induced by MRFHRV. These results were further validated by CCK8 assay in mouse embryonic stem cells and GFAP staining in embryonic brain tissue. This study indicated that chemotherapeutic and antiepileptic agents induced NTDs might through predicted targets TP53, MAPK1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN and multiple signaling pathways. More caution was required for the clinical administration for women with childbearing potential and pregnant. [ABSTRACT FROM AUTHOR]

Chemotherapy is the main method for controlling pancreatic cancer metastasis but the prevalent chemotherapy resistance limits its utilization. The response of oxidation and inflammation often promotes pancreatic cancer progression and chemo‐resistance. It is critical to explore the potential natural products with few side effects to control inflammatory responses and understand the related mechanisms. Quercetin is a flavonoid widely found in numerous vegetables, fruits, and foods and is thought to have antioxidant and anti‐inflammatory properties, which may be associated with improvement of chemotherapy sensitivity during pancreatic cancer treatment. Quercetin may sensitize pancreatic cancer cells to the chemotherapeutic agents, including bromodomain and extraterminal domain inhibitors (BETI), daunorubicin, gemcitabine, sulforaphane, doxorubicin, and tumor necrosis factor‐related signaling apoptosis‐inducing ligand (TRAIL). Meanwhile, during the chemo‐resistance therapy, many signaling molecules are involved with toll‐like receptor 4 (TLR4)‐mediated oxidative and inflammatory pathway. The effects of quercetin on other oxidative and inflammatory pathways were also explored. Quercetin may exert antitumor activity during the prevention of pancreatic cancer progression by regulating oxidative and inflammatory networks, which can promote immune escape of cancer cells by inducing immunosuppressive cytokines. Studying these patterns will help us to better understand the functional role of quercetin in the improvement of pancreatic cancer chemo‐sensitivity. Practical applications: Chemotherapy is the major way for treating pancreatic cancer metastasis but the prevalent chemotherapy resistance caused by oxidative and inflammatory responses limits its utilization. It is necessary to explore the potential natural products with few side effects to prevent the oxidative and inflammatory responses. Quercetin is a flavonoid widely found in numerous vegetables, fruits, and foods and is thought to have antioxidant and anti‐inflammatory properties, which may be associated with improvement of chemotherapy sensitivity of pancreatic cancer treatment by sensitizing pancreatic cancer cells to various chemotherapeutic agents via the regulation of oxidative and inflammatory networks. Studying these patterns will help us to better understand the functional role of quercetin in the improvement of pancreatic cancer chemo‐sensitivity. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is a common childhood sarcoma, and its treatment is hindered by adverse effects, chemoresistance, and recurrence. Interleukin (IL)-6 production by tumors plays a significant role in inflammation, carcinogenesis, and metastasis. This study aimed to investigate the antiproliferative potential of luteolin derivatives in OS and to evaluate interleukin production. MG-63, Saos-2, HOS, and 143B human OS cell lines were incubated with luteolin and eight derivatives containing hydroxy, chlorine, or alkyl substitutions. The cell viability and growth were evaluated in the presence of these compounds. Apoptosis was also examined through the analysis of the Bax expression and caspase-3 activity. Finally, the gossypetin effects were measured regarding the production of proinflammatory cytokines interleukin (IL)-6, IL-1β, and IL-12p70. Our findings show that gossypetin was the most potent compound, with proliferation-suppressing activities that induced a series of critical events, including the inhibition of the cell viability and growth. Apoptosis was associated with enhanced caspase-3 activity and increased Bax expression, indicating the involvement of the intrinsic pathway of apoptosis. Moreover, pre-/co-treatment with gossypetin significantly reduced the autocrine production of proinflammatory cytokines. Further investigation is required; nevertheless, considering the link between inflammation, carcinogenesis, and metastasis in OS, our findings suggest that gossypetin exhibits anti-proliferative and anti-inflammatory properties that are potentially relevant in the clinical context.

The ketone bodies, sodium and lithium salts of acetoacetate (AcAc) and sodium 3-hydroxybutyrate (3-HB; commonly called beta-hydroxybutyrate) have been found to inhibit the proliferation of cancer cells. Previous studies have suggested that lithium itself may be an inhibiting agent but may be additive or synergistic with the effect of AcAc. We previously found that sodium acetoacetate (NaAcAc) inhibits the growth of human colon cancer cell line SW480. We report here similar results for several other cancer cell lines including ovarian, cervical and breast cancers. We found that NaAcAc does not kill cancer cells but rather blocks their proliferation. Similar inhibition of growth was seen in the effect of lithium ion alone (as LiCl). The effect of LiAcAc appears to be due to the combined effects of acetoacetate and the lithium ion. The ketone bodies, when given together with chemotherapeutic agents, rapamycin, methotrexate and the new peptide anti-cancer agent, PNC-27, substantially lowers their IC50 values for cancer cell, killing suggesting that ketone bodies and ketogenic diets may be powerful adjunct agents in treating human cancers.

Patients on Cancer chemotherapeutic agents often develop nail changes most of which are only cosmetic concern and disappear on drug withdrawal. But some nail changes can be painful and disabling thereby affecting quality of life substantially. Different components of the nail unit include the nail matrix, nail bed, nail plate, the hyponychium, lunula, the proximal and lateral nail folds. In this article we review the nail changes induced by chemotherapeutics and targeted anticancer drugs, preventive measures and treatment options available.

Autophagy is a catabolic process in which an organism responds to its nutrient or metabolic emergencies. It involves the degradation of cytoplasmic proteins and organelles by forming double-membrane vesicles called "autophagosomes." They sequester cargoes, leading them to degradation in the lysosomes. Although autophagy acts as a protective mechanism for maintaining homeostasis through cellular recycling, it is ostensibly a cause of certain cancers, but a cure for others. In other words, insufficient autophagy, due to genetic or cellular dysfunctions, can lead to tumorigenesis. However, many autophagy modulators are developed for cancer therapy. Diverse nanoparticles have been documented to induce autophagy. Also, the highly stable nanoparticles show blockage to autophagic flux. In this review, we revealed a general mechanism by which autophagy can be induced or blocked via nanoparticles as well as several studies recently performed to prove the stated fact. In addition, we have also elucidated the paradoxical roles of autophagy in cancer and how their differential role at different stages of various cancers can affect its treatment outcomes. And finally, we summarize the breakthroughs in cancer disease treatments by using metallic, polymeric, and liposomal nanoparticles as potent autophagy modulators. [ABSTRACT FROM AUTHOR]

Harnessing the broad immunostimulatory capabilities of chemotherapy in combination with immune checkpoint inhibitors has improved immunotherapy outcomes in patients with cancer. Certain chemotherapeutic agents can extensively modify the tumor microenvironment (TME), resulting in the reprogramming of local immune responses. Although chemotherapeutic agents with an enhanced generation of potent anti-tumor immune responses have been tested in preclinical animal models and clinical trials, this strategy has not yet shown substantial therapeutic efficacy in selected difficult-to-treat cancer types. In addition, the efficacy of chemotherapeutic agent-based monotherapy in eliciting a long-term antitumor immune response is restricted by the immunosuppressive TME. To enhance the immunomodulatory effect of chemotherapy, researchers have made many attempts, mainly focusing on improving the targeted distribution of chemotherapeutic agents and designing combination therapies. Here, we focused on the mechanisms of the anti-tumor immune response to chemotherapeutic agents and enumerated the attempts to advance the use of chemo-immunotherapy. Furthermore, we have listed the important considerations in designing combinations of these drugs to maximize efficacy and improve treatment response rates in patients with cancer. [ABSTRACT FROM AUTHOR]

Death receptor 5 (DR5) is a membrane protein that mediates exogenous apoptosis. Based on its function, it is considered to be a target for the treatment of cancers including prostate cancer. It is encouraging to note that a number of drugs targeting DR5 are now progressing to different stages of clinical trial studies. We collected 38 active compounds that could produce anti-prostate-cancer effects by modulating DR5, 28 of which were natural compounds and 10 of which were synthetic compounds. In addition, 6 clinically used chemotherapeutic agents have also been shown to promote DR5 expression and thus exert apoptosis-inducing effects in prostate cancer cells. These compounds promote the expression of DR5, thereby enhancing its function in inducing apoptosis. When these compounds were used in combination with the natural ligand of DR5, the number of apoptotic cells was significantly increased. These compounds are all promising for development as anti-prostate-cancer drugs, while most of these compounds are currently being evaluated for their anti-prostate-cancer effects at the cellular level and in animal studies. A great deal of more in-depth research is needed to evaluate whether they can be developed as drugs. We collected literature reports on small molecules against prostate cancer through modulation of DR5 to understand the current dynamics in this field and to evaluate the prospects of small molecules against prostate cancer through modulation of DR5. [ABSTRACT FROM AUTHOR]

Research on cancer treatment is always of great importance because of the extensive and difficult treatment options and side effects of chemotherapeutic agents. Due to this, novel techniques for cancer treatment are the need of the day. Nowadays, nanotechnology is of great interest for its applications as diagnostic tools, theragnostic, contrasting agents, and vehicles for delivering drugs. Nanoparticles (NPs) are made up of biocompatible and biodegradable polymers that improve the pharmacokinetic and pharmacodynamic properties of drugs, reduce side effects, improve stability, prolong the release of drug, and reduce the dosing frequency. Poly (lactic-co-glycolic acid) (PLGA) is FDA-approved synthetic polymer which can be used to formulate NPs that can be targeted to a specific site for the safe and effective delivery of drugs. PLGA-based NPs can be used for a variety of cancer therapies including tumor-targeted drug delivery, gene therapy, hyperthermia, and photodynamic therapy. This article discusses the method of preparation, characterization, encapsulation of chemotherapeutic drugs, effect of physicochemical properties of PLGA- based NPs, and how we can exploit these aspects through various methods of preparation for drug loading, biodistribution, target specificity, and their use in cancer treatment. Along with these targeting strategies, gene therapy, cancer immunotherapy, and various applications have also been discussed. This article also aims to discuss the incorporation of diagnostic tools and therapeutic moiety in one versatile formulation of PLGA-NPs and the difficulties faced in translating this promising tool to clinical use. [ABSTRACT FROM AUTHOR]