Types Of Anticancer Drugs Research Articles

Accuracy of gravity based automatic infusion system applied to chemoport for intravenous infusion.

191 Background: When a vesicant drug is administered to the peripheral vein, a gravity drip method rather than an peristaltic infusion pump is recommended. In addition, it is reported that the gravity based pump has less particle generation than the peristaltic pump that injects fluid through constant peristaltic movement. However, it is pointed out that the disadvantage of gravity based pump is that the rate of administration can easily change according to the change in the location of the injection site. We evaluate the accuracy of new gravity based pump (pressure-sensitive speed control fluid injection device, Accudrip made by Hanvit MD ) at various injection rates and hanging heights common to hospital settings. Methods: The accuracy and safety of the intravenous (IV) flow controller were evaluated for patients receiving IV chemotherapy in the oncology department. It was verified whether the accurate injection rate could be maintained even in various fluid heights, fluid amounts, and types of anticancer drugs that could affect the injection rate. Various anticancer drugs, including immune checkpoint inhibitor, were mixed with 250 ml/500 ml of normal saline and administered for 30 min/60 min, and glucose 500 ml/1000 ml was administered for 60 min/120 min to measure accuracy, each progressed 25 times. Medical staff were surveyed on the ease and limitations of medical practice for each peristaltic infusion pump and new gravity based pump. In addition, side effects occurring in patients during fluid administration were recorded. Results: The mean degree of error in the estimated end time of gravity based automatic infusion system was 3.09% (2.09 ~ 4.10). The error of the gravity based automatic infusion system was statistically significant depending on the patient age (p=.001) and the infusion time (p=.016), but the degree of error according to the type of fluids (p=.302) and fluid concentration (p=.844) was not statistically significant. Among the subjects of the study, nurses' satisfaction with the application of gravity based pump was 4.10 (±0.62) out of 5, and among the general characteristics of nurses, age ( p<.078), and working department (p<.91) did not show a statistically significant difference, but work experience ( p <.021) showed a statistically significant difference. Conclusions: The accuracy of Gravity based automatic infusion system was determined because the degree of error in the expected end time of infusion was not significant according to the infusion variable. In a survey of nurses who have used gravity based pump directly, it was found that the ease of use and satisfaction were similar to those of the conventional peristaltic pump. These findings will contribute greatly to the precise drug administration (over or under-administration) and minimization of adverse events in real-world hospital settings.

Potential of Organometallic Complex Compounds as Anticancer Drugs: A Review

Cancer is one of the deadliest diseases in the world. Currently, there are various types of anticancer drugs that are used to treat cancer, but they still have various side effects that can interfere with the quality of life of patients. Organometallic complexes (OCOs) are chemical compounds consisting of metal atoms bonded to carbon atoms. OCOs have various potential to be used as anticancer drugs, including their ability to specifically target cancer cells, inhibit cancer cell growth, and reduce the side effects of other anticancer drugs. The mechanism of action of OCOs involves interactions with nucleophilic molecules within the cell, including DNA, RNA, and proteins, as well as the formation of additional platinum products. In this review, we will discuss organometallic compounds that can function as anticancer drugs, such as platinum, ruthenium, iron, carboplatin, and oxaliplatin, which have been shown to be effective in fighting cancer. We will also discuss the mechanism of action of these compounds in cancer cells and the types of cancer cells that can be treated with organometallic compounds.

Efficient delivery of anticancer drugs using functionalized-Ag-decorated Fe3O4@SiO2 nanocarrier with folic acid and β-cyclodextrin

Nanocarrier surface functionalization has been widely regarded as a promising approach for achieving precise and targeted drug delivery systems. In this work, the fabrication of functionalized-Ag-decorated Fe3O4@SiO2 (Fe3O4@SiO2-Ag) nanocarriers with folic acid (FA) and β-cyclodextrin (BCD) exhibit a remarkable capacity for delivering two types of anticancer drugs, i.e., doxorubicin (DOX) and epirubicin (EPI), into cancer cells. The effective functionalization of Fe3O4@SiO2-Ag nanoparticles has been achieved through the use of cysteine (Cys) as an anchor for attaching FA and BCD via EDC-NHS coupling and Steglich esterification methods, respectively. The findings indicate that surface functionalization had no significant impact on the physicochemical characteristics of the nanoparticles. However, it notably affected DOX and EPI loading and release efficiency. The electrostatic conjugation of DOX/EPI onto the surface of Fe3O4@SiO2-Ag/Cys/FA and Fe3O4@SiO2-Ag/Cys/BCD exhibited maximum loading efficiency of 50–60% at concentration ratio of DOX/EPI to nanoparticles of 1:14. These nanocarriers also achieved an 40–47% DOX/EPI release over 36 days. Furthermore, the drug-loaded functionalized-nanocarrier showed cytotoxic effects on SK-MEL-2 cells, as demonstrated by an in vitro MTT assay. This suggests that the as-prepared functionalized-nanoparticles have promise as a carrier for the efficient anticancer drugs.

#1187 Acute kidney injury and tubulointerstitial nephritis following prescription of anticancer drugs: VigiBase analysis

Abstract Background and Aims Anticancer drugs can have varying effects on the kidneys, depending on their characteristics. Various anticancer drugs may be nephrotoxic and can potentially cause renal impairment. We aimed to analyze the risk of renal adverse reactions according to different types of anticancer drugs using a global reporting system. Method We conducted an analysis on VigiBase, the World Health Organization pharmacovigilance database from Dec 1967 to Jul 2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) compares observed and expected values to find the associations of each category of anticancer drugs with acute kidney injury (AKI) and tubulointerstitial nephritis (TIN). Results We observed 32,722 AKI and 2,056 TIN reports which were reported as anticancer drug-related renal adverse reactions. Noteworthy trends emerged in AKI reports following anticancer drugs: cytotoxic therapies consistently dominated with 13,925 cases, while AKI cases related to targeted therapies and immunotherapies surged to 14,236 and 3,816 cases over three decades, respectively. Notably, TIN exhibited a significant increase, particularly after the popular usage of immunotherapy between 2015 and 2020, surpassing other categories of anticancer drugs. The highest disproportionality signal for AKI was associated with immunotherapies (ROR, 8.92; confidence interval [CI], 8.63–9.21, followed by cytotoxic therapies (ROR, 7.14; 95% CI, 7.01–7.26), targeted therapies (ROR, 5.83; 95% CI, 5.73–5.93), and hormone therapies (ROR, 2.59; 95% CI, 2.41–2.79). In the case of TIN, a significantly higher disproportionality signal was found for immunotherapies (ROR, 21.74; 95% CI, 20.39–23.18), followed by cytotoxic therapies (ROR, 2.60; 95% CI, 2.40–2.82), and targeted therapies (ROR, 1.54; 95% CI, 1.40–1.69). Hormone therapies did not exhibit a significant disproportionality signal. Separate analyses were also conducted for the ROR of AKI and TIN for each individual anticancer drug. Conclusion AKI and TIN were substantially observed following the administration of anticancer drugs. Noticeably, renal adverse reactions following immunotherapy, which have been experiencing an increase in utilization, were more prominent than other types of anticancer drugs. Clinicians should consider the increased risk of renal adverse reactions after specific anticancer drugs.

Vitamin D-metabolizing enzyme CYP24A1 affects oncogenic behaviors of oral squamous cell carcinoma and its prognostic implication.

Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.

Green synthesis of anti-cancer drug-loaded gold nanoparticles for low-intensity pulsed ultrasound targeted drug release.

In the present work, we have designed a one-pot green protocol in which anti-cancer drugs (curcumin and doxorubicin) can be directly loaded on the surface of gold nanoparticles during their formation. We have further demonstrated that low-intensity pulsed ultrasound (LIPUS) can be used to effectively induce the release of anti-cancer drugs from the surface of gold nanoparticles in an ex vivo tissue model. With this protocol, gold nanoparticles can be easily loaded with different types of anticancer drugs, irrespective of their affinity towards water, and even hydrophobic molecules, like curcumin, can be attached onto the gold nanoparticles in an aqueous medium. The method is very simple and straightforward and does not require stirring or mechanical shaking. The drug molecules interact with the gold seeds formed during the reduction and growth process and modulate the final morphology into a spherical shape. A black-colored colloidal solution of gold nanowire networks is formed in the absence of these anti-cancer drug molecules in the reaction mixture. We used hyperspectral-enhanced dark field microscopy to examine the uptake of gold nanoparticles by breast cancer cells. Upon exposure to LIPUS, the release of the anti-cancer drug from the particle surface can be quantified by fluorescence measurements. This release of drug molecules along with trisodium citrate from the surface of gold nanoparticles by ultrasound resulted in their destabilization and subsequent aggregation, which could be visually observed through the change in the color of colloidal sol. Cancer cell viability was studied by MTT assay to examine the efficacy of this nanoparticle-based drug delivery system. Ultraviolet-visible spectroscopy, dynamic light scattering (DLS), and transmission electron microscope (TEM) analysis were used to characterize the nanoparticles and quantify anti-cancer drug release.

Pharmacological class effects of anticancer drugs: opportunities for decreasing healthcare spending

In the field of general medicine, class effects, or therapeutic interchangeability, have been declared for several families of drugs including statins, calcium channel blockers and ACE inhibitors. The existence of...

Machine Learning-Assisted Automatically Electrochemical Addressable Cytosensing Arrays for Anticancer Drug Screening.

The high-throughput and accurate screening of anticancer drugs is crucial to the preclinical assessment of candidate drugs and remains challenging. Herein, an automatically electrochemical addressable cytosensor (AEAC) for the efficient screening of anticancer drugs is reported. This sensor consists of sectionalized laser-induced graphene arrays decorated by the rhombohedral TiO2 and spherical Pt nanoparticles (LIG-TiO2-Pt) with high electrocatalytic activity for H2O2 and a homemade Ag/Pt electrode couple fixed onto the robot arm. The immobilization of laminin on the surface of LIG-TiO2-Pt can promote its biocompatibility for the growth and proliferation of various tumor cells, which empowers the in situ monitoring of H2O2 directly released from these live cells for drug screening. A machine learning (ML) algorithm is employed to eliminate the possible random or systematic errors of AEAC, realizing rapid, high-throughput, and accurate prediction of different types of anticancer drugs. This ML-assisted AEAC provides a powerful approach to accelerate the evolution of sensing-served tumor therapy.

Bioinspired Nanocomplexes Comprising Phenolic Acid Derivative and Human Serum Albumin for Cancer Therapy.

Inspired by the natural phenomenon of phenolic-protein interactions, we translate this "naturally evolved interaction" to a "phenolic acid derivative based albumin bound" technology, through the synthesis of phenolic acid derivatives comprising a therapeutic cargo linked to a phenolic motif. Phenolic acid derivatives can bind to albumin and form nanocomplexes after microfluidic mixing. This strategy has been successfully applied to different types of anticancer drugs, including taxanes, anthraquinones, etoposides, and terpenoids. Paclitaxel was selected as a model drug for an in-depth study. Three novel paclitaxel-phenolic acid conjugates have been synthesized. Molecular dynamics simulations provide insights into the self-assembled mechanisms of phenolic-protein nanocomplexes. The nanocomplexes show improved pharmacokinetics, elevated tolerability, decreased neurotoxicity, and enhanced anticancer efficacies in multiple murine xenograft models of breast cancer, in comparison with two clinically approved formulations, Taxol (polyoxyethylated castor oil-formulated paclitaxel) and Abraxane (nab-paclitaxel). Such a robust system provides a broadly applicable platform for the development of albumin-based nanomedicines and has great potential for clinical translation.

PH-sensitive and targeted core-shell and yolk-shell microcarriers for in vitro drug delivery

Recently, biocompatible and high-performance drug carriers have revolutionized drug delivery systems. This study aims to design and develop a slow, targeted delivery system of curcumin (C) and gemcitabine (G) as two types of anticancer drugs. Three-layer shells containing two types of biodegradable polymers i.e. chitosan (CHI) and poly (methacrylic acid-coethyleneglycol dimethacrylate) (ME) were coated on Fe3O4 (MG) and/or MG@SiO2 cores. Silica removal in the next stage produced core-shell and yolk-shell structures, as confirmed via transmission electron microscopy (TEM). The loading and releasing of drugs in phosphate buffer saline (PBS) with pH = 5.5 and pH = 7.4 were examined via UV–Vis spectroscopy. In both types of microparticles, acceptable loading (LE%) and encapsulation (EE%) efficiencies were obtained. Nevertheless, the LE% values of yolk-shell microparticles (H-MG@CHI.ME.CHI) were significantly higher than those of the core-shell microparticles (MG@CHI.ME.CHI). This higher loading capacity arises from the presence of cavities in the yolk-shell structure. Both microcapsules showed a release rate of over 80% for both drugs at acidic pH, while the release of drugs was relatively lower in the neutral environment. Further, the cytotoxic effect of microparticles, determined through the MTT method, was consistent with the results of drug release.

Implications of glutathione-S transferase P1 in MAPK signaling as a CRAF chaperone: In memory of Dr. Irving Listowsky.

Glutathione-S transferase P1 (GSTP1) is one of the glutathione-S transferase isozymes that belong to a family of phase II metabolic isozymes. The unique feature of GSTP1 compared with other GST isozymes is its relatively high expression in malignant tissues. Thus, clinically, GSTP1 serves as a tumor marker and as a refractory factor against certain types of anticancer drugs through its primary function as a detoxifying enzyme. Additionally, recent studies have identified a chaperone activity of GSTP1 involved in the regulation the function of various intracellular proteins, including factors of the growth signaling pathway. In this review, we will first describe the function of GSTP1 and then extend the details onto its role in the mitogen-activated protein kinase signal pathway, referring to the results of our recent study that proposed a novel autocrine signal loop formed by the CRAF/GSTP1 complex in mutated KRAS and BRAF cancers. Finally, the possibilities of new therapeutic approaches for these cancers by targeting this complex will be discussed.

Reduced neighborhood degree-based topological indices on anti-cancer drugs with QSPR analysis

Human body is concocted with trillions of cells which normally grows over the life time and gets divided as needed and they die when the cells got old or become abnormal. But as the cells keep producing the new cells, if the old or abnormal cells don’t die, the cancer starts. These cancer cells grow uncontrollably and they crowd the normal cells and hence the body does not function the way it is supposed to. Several types of anti-cancer drugs have been developed which attack the cancer cells and causing less damage to the normal cells. The chemical based studies show the connection between characteristics of alkanes and anti-cancer drugs namely, enthalpy, molar volume, boiling point and so on with their molecular structures. In this paper, we have defined various reduced neighborhood topological indices and calculated the physio-chemical properties of some anti-cancer drugs. Also, the QSPR analysis for these newly introduced indices are studied and we exhibit the good correlation with characteristics on these drugs.

A new method for determining drug half-life and evaluating stability

In the measurement system of 4-5 different types of anticancer drugs and commonly used drugs and corresponding solvents, the microcalorimetry was the main research method to determine the dissolving enthalpy of the drug in the corresponding solvent to study the dissolution behaviour of drugs in solvents. According to the established mathematical model of thermodynamics, the dissolution half-life of drugs in the corresponding solvents is calculated, the kinetic equation, kinetic parameters and thermodynamic parameters in the dissolution process are established, and the database of thermodynamic and kinetic parameters of the anticancer drugs and commonly used drugs is established, which provides a theoretical basis for the stability evaluation and clinical application of drugs..

A One-Two-Three Multifunctional System for Enhanced Imaging and Detection of Intracellular MicroRNA and Chemogene Therapy.

Simultaneous imaging, diagnosis, and therapy can offer an effective strategy for cancer treatment. However, the complex probe design, poor drug release efficiency, and multidrug resistance remain tremendous challenges to cancer treatment. Here, a novel one-two-three system is built for enhanced imaging and detection of miRNA-21 (miR-21) overexpressed in cancer cell and chemogene therapy. The system consists of dual-mode DNA robot nanoprobes assembled by two types of hairpin DNAs and three-way branch DNAs modified on gold nanoparticles, with intercalating anticancer drugs (doxorubicin), into DNA duplex GC base pairs. In the system, via intracellular ATP-accelerated cyclic reaction triggered by miR-21, fluorescence and SERS signals were alternated with DNA structure switch, and the precise SERS detection of miRNA and fluorescence imaging oriented "on-demand" release of two types of anticancer drugs (anti-miR-21 and Dox) are achieved. Thus, "one-two-three" means one kind of miR-21-triggered endogenous substance accelerated cyclic reaction, two modes of signal switch, and three functions including enhanced imaging, detection, and comprehensive treatment. The one-two-three system has some notable merits. First, ATP as an endogenous substance promotes DNA structure switching and accelerates the cyclic reaction. Second, the treatment with a dual-mode signal switch is more reliable and accurate and can provide more abundant information than a single-mode treatment platform. Thus, the imaging and detection of intracellular miRNA and effective comprehensive therapy are realized. In vivo results indicate that the system can provide new insights and strategies for diagnosis and therapy.

β-Thujaplicin Enhances TRAIL-Induced Apoptosis via the Dual Effects of XIAP Inhibition and Degradation in NCI-H460 Human Lung Cancer Cells.

Background: β-thujaplicin, a natural tropolone derivative, has anticancer effects on various cancer cells via apoptosis. However, the apoptosis regulatory proteins involved in this process have yet to be revealed. Methods: Trypan blue staining, a WST-8 assay, and a caspase-3/7 activity assay were used to investigate whether β-thujaplicin sensitizes cancer cells to TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Additionally, western blotting was performed to clarify the effects of β-thujaplicin on X-linked inhibitor of apoptosis protein (XIAP) in NCI-H460 cells and a fluorescence polarization binding assay was used to evaluate the binding-inhibitory activity of β-thujaplicin against XIAP-BIR3. Results: β- and γ-thujaplicins decreased the viability of NCI-H460 cells in a dose-dependent manner; they also sensitized the cells to TRAIL-induced cell growth inhibition and apoptosis. β-thujaplicin significantly potentiated the apoptosis induction effect of TRAIL on NCI-H460 cells, which was accompanied by enhanced caspase-3/7 activity. Interestingly, β-thujaplicin treatment in NCI-H460 cells decreased XIAP levels. Furthermore, β-thujaplicin was able to bind XIAP-BIR3 at the Smac binding site. Conclusions: These findings indicate that β-thujaplicin could enhance TRAIL-induced apoptosis in NCI-H460 cells via XIAP inhibition and degradation. Thus, the tropolone scaffold may be useful for designing novel nonpeptidic small-molecule inhibitors of XIAP and developing new types of anticancer drugs.

An Analysis of Mechanisms for Cellular Uptake of miRNAs to Enhance Drug Delivery and Efficacy in Cancer Chemoresistance.

Up until recently, it was believed that pharmaceutical drugs and their metabolites enter into the cell to gain access to their targets via simple diffusion across the hydrophobic lipid cellular membrane, at a rate which is based on their lipophilicity. An increasing amount of evidence indicates that the phospholipid bilayer-mediated drug diffusion is in fact negligible, and that drugs pass through cell membranes via proteinaceous membrane transporters or carriers which are normally used for the transportation of nutrients and intermediate metabolites. Drugs can be targeted to specific cells and tissues which express the relevant transporters, leading to the design of safe and efficacious treatments. Furthermore, transporter expression levels can be manipulated, systematically and in a high-throughput manner, allowing for considerable progress in determining which transporters are used by specific drugs. The ever-expanding field of miRNA therapeutics is not without its challenges, with the most notable one being the safe and effective delivery of the miRNA mimic/antagonist safely to the target cell cytoplasm for attaining the desired clinical outcome, particularly in miRNA-based cancer therapeutics, due to the poor efficiency of neo-vascular systems revolting around the tumour site, brought about by tumour-induced angiogenesis. This acquisition of resistance to several types of anticancer drugs can be as a result of an upregulation of efflux transporters expression, which eject drugs from cells, hence lowering drug efficacy, resulting in multidrug resistance. In this article, the latest available data on human microRNAs has been reviewed, together with the most recently described mechanisms for miRNA uptake in cells, for future therapeutic enhancements against cancer chemoresistance.

Overcoming immune resistance by sequential prodrug nanovesicles for promoting chemoimmunotherapy of cancer

Chemotherapy by certain types of anticancer drugs (e.g., doxorubicin (DOX) and oxaliplatin (OXA)) can elicit antitumor immune response by promoting immunogenic cell death (ICD) of the tumor cells. However, ICD-based chemoimmunotherapy is severely impaired by non-specific distribution of the chemotherapeutics and T lymphocyte-induced immune resistance. To address these challenges, we herein reported a sequential prodrug nanovesicle specifically designed for enhancing drug delivery to the tumor tissues and reducing the immunological resistance of the tumor cells. The prodrug nanovesicles were composed of fluorophore IR-1061, chemotherapeutic DOX, and a prodrug of bromodomain-containing protein 4 inhibitor (BRD4i) JQ1. Upon 1064 nm laser irradiation, IR-1061 induced mild hyperthermia for triggering NIR-Ⅱ fluorescence imaging-guided drug release at the tumor site. DOX promoted intratumoral infiltration of the cytotoxic T lymphocytes (CTLs) by inducing ICD of the tumor cells. Meanwhile, JQ1 blocked IFN-γ-induced upregulation of programmed death ligand 1 (PD-L1) to reduce the adaptive immune resistance. In combination with laser irradiation, the prodrug nanovesicles remarkably inhibited growth of both 4T1 breast and CT26 colorectal tumors, and suppressed lung metastasis of 4T1 breast tumor in the immunocompetent mouse model. The prodrug nanoplatform reported herein might provide a novel insight for promoting chemoimmunotherapy of cancers by overcoming PD-L1-dependent immune evasion through the IFN-γ-BRD4-PD-L1 axis.

Hyaluronic acid thiol modified injectable hydrogel: Synthesis, characterization, drug release, cellular drug uptake and anticancer activity

Dimethyl sulfoxide (DMSO) is an excellent solvent for various types of anticancer drugs. Here, beyond that, it can participate in a disulfide bond crosslink between sulfhydryl (-SH) modified hyaluronic acid (HA-SH) molecules to form the hydrogel. Thus, during the above crosslink process, the dissolved drug in DMSO could be effectively loaded inside the hydrogels' porous structures as an injectable peritumoral implant. The loaded drugs can be sustained released through hydrogel swelling and degradation around the tumor tissue to suppress tumor growth. In this paper, the above hydrogel was used as a peritumoral drug-loaded implant for chemotherapeutics, photosensitizer, and photothermal reagent, respectively, for chemotherapy, photodynamic therapy, and photothermal therapy in cancer treatment. Therefore, this DMSO involved HA-SS-HA (HA, hyaluronic acid; -SS-, disulfide bond) hydrogel fabrication method is simple and widely applicable for drug-loaded peritumoral implant preparation.

Cathepsin B-Responsive Liposomes for Controlled Anticancer Drug Delivery in Hep G2 Cells.

In recent decades, several types of anticancer drugs that inhibit cancer cell growth and cause cell death have been developed for chemotherapeutic application. However, these agents are usually associated with side effects resulting from nonspecific delivery, which may induce cytotoxicity in healthy cells. To reduce the nonspecific delivery issue, nanoparticles have been successfully used for the delivery of anticancer drugs to specific target sites. In this study, a functional polymeric lipid, PEG-GLFG-K(C16)2 (PEG-GLFG, polyethylene glycol-Gly-Leu-Phe-Gly-Lys(C16)2), was synthesized to enable controlled anticancer drug delivery using cathepsin B enzyme-responsive liposomes. The liposomes composed of PEG-GLFG/DOTAP (1,2-dioleoyl-3-trimethylammonium-propane (chloride salt))/DPPC (dipalmitoylphosphatidylcholine)/cholesterol were prepared and characterized at various ratios. The GLFG liposomes formed were stable liposomes and were degraded when acted upon by cathepsin B enzyme. Doxorubicin (Dox) loaded GLFG liposomes (GLFG/Dox) were observed to exert an effective anticancer effect on Hep G2 cells in vitro and inhibit cancer cell proliferation in a zebrafish model.

Pancreatic cancer drug-sensitivity predicted by synergy of p53-Activator Wnt Inhibitor-2 (PAWI-2) and protein biomarker expression

Today, pancreatic cancer (PC) is a major health problem in the United States. It remains a challenge to develop efficacious clinically useful PC therapies. New avenues, based on translational approaches and innovative validated biomarkers could be a preclinical option to evaluate PC drug candidates or drug combinations before clinical trials. Herein, we describe evaluation of combination therapies by incorporating a novel pathway modulator, p53-Activator Wnt Inhibitor-2 (PAWI-2) with other FDA-approved cancer drugs that have been used in PC clinical trials. PAWI-2 is a potent inhibitor of drug-resistant PC cells that has been shown to selectively ameliorate human pancreatic cancer stem cells (i.e., hPCSCs, FGβ3 cells). In the present study, we showed PAWI-2 produced therapeutic synergism with certain types of anti-cancer drugs. These drugs themselves oftentimes do not ameliorate PC cells (especially PCSCs) due to high levels of drug-resistance. PAWI-2 has the ability to rescue the potency of drugs (i.e., erlotinib, trametinib) and inhibit PC cell growth. Key molecular regulators of PAWI-2 could be used to predict synergistic/antagonistic effects between PAWI-2 and other anti-cancer drugs. Anti-cancer results showed potency could be quite accurately correlated to phosphorylation of optineurin (OPTN) in PC cells. Synergism/antagonism was also associated with inhibition of PCSC marker SOX2 that was observed in FGβ3 cells. Synergism broadens the potential use of PAWI-2 as an adjunct chemotherapy in patients with PC that have developed resistance to first-line targeted therapies or chemotherapies.