Search

Objectives: Colorectal cancer is one of the most common cancers worldwide. However, surgical intervention and chemotherapy provide only limited benefits for the recovery and survival of patients. The anticarcinogenic effect of genistein has attracted attention because epidemiological studies have shown that soybean consumption is associated with a decrease in the incidence of cancer. There are limited studies on the effects of genistein in colorectal carcinoma cells. We aimed to investigate the cytotoxic, genotoxic, and apoptotic effects of genistein in SW480 and SW620 colon adenocarcinoma cells treated with 5-fluorouracil, the basis of chemotherapy, and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) ligand, the mediator of apoptosis, both alone and in combination. Materials and Methods: Cytotoxicity and genotoxicity were determined by MTT and comet assays, respectively. The apoptotic effects were evaluated by reverse transcription-polymerase chain reaction assay, with the additional use of Annexin V FITC, mitochondrial membrane potential (MMP), caspase 3, 8, and 9 activity, and reactive oxygen species (ROS) assay kits. Results: According to our findings, genistein, 5-fluorouracil, and TRAIL had synergistic apoptotic effects because of DR5 upregulation, ROS production, and DNA damage, which were mediated by increased caspase-8, and -9 activity and decreased MMP. Conclusion: The applied combinations of these compounds may contribute to the resistance problem that may occur in treating colorectal cancer, with a decrease in DcR1 and XIAP genes. [ABSTRACT FROM AUTHOR]

New system compromising of chitosan nanoparticles encapsulated pre-synthesized selenium nanoparticles in the presence of 5-fluorouracil was successfully prepared and used for cancer antiproliferation. Selenium nanoparticles were synthesized using ascorbic acid as reducing agent under mild condition. Chitosan nanoparticles were prepared via ionic gelation technique using sodium tri-polyphosphate. Characterization of the prepared nanoparticles was carried out using FTIR, TEM, XRD, TGA and dynamic light scattering (DLS). The results displayed the formation of selenium nanoparticles with an average size 20 nm and chitosan nanoparticles with an average size 207 and 250 nm for neat nano-chitosan and chitosan incorporated 5-fluorouracil/selenium nanoparticles, respectively. The encapsulated nanocomposites were tested for treatment of cancer cell of human colorectal carcinoma (HCT-116), human liver carcinoma (HepG-2), and human breast adenocarcinoma MCF-7. The results indicated the potent cytotoxic activities of all nanocomposite toward the tested cells with enhanced anticancer activity rather than the single drug or neat selenium nanoparticle. All composites were tested against non-tumor fibroblast-derived cell line (BJ) and demonstrated very low cytotoxicity. [ABSTRACT FROM AUTHOR]

The reactivity of 5-fluoro-1H,3H-pyrimidine-2,4-dione (5-fluorouracil), which is widely used to treat cancer, toward superoxide radical anion (O2•−) and hydroperoxyl radical (HO2•) was investigated using density functional theory (DFT) calculations. 5-Fluorouracil is a pyrimidine analog with cytotoxic effects on cancer cells and potential ecotoxicology as a recalcitrant compound to the natural environment; therefore, clarifying its chemical degradation mechanism is difficult by way of in vivo and in vitro experiments but important for further usage. The DFT results clarified that the oxidation of 5-fluorouracil by O2•− or HO2• in water is feasible through a proton-coupled electron transfer (PCET) mechanism. In addition, a concerted PCET pathway between 5-fluorouracil and HO2• preformed via the protonation of O2•− is proposed. In this pathway, the amine group at the first position of 5-fluorouracil acts as a reaction site for the concerted PCET after forming a prereactive complex via a hydrogen bond. Considering that the actual oxidant along the PCET pathways is HO2• with a short lifetime, the biodegradability of 5-fluorouracil by O2•− (HO2•) is governed by the complex formation step and the concerted PCET. [ABSTRACT FROM AUTHOR]

Posterior capsular opacification (PCO) is the most common complication that occurs after intraocular lens (IOL) implantation in cataract therapy. In recent years, IOLs have been developed as drug delivery platforms, but concerns over the safety of uncontrolled proliferative drug release have arisen. Therefore, a controlled drug release strategy is needed for safer PCO prevention. In this study, a new monomer contained coumarin group was introduced in material preparation, and poly(ethylene gly co l phenyl ether methacrylate- co -2-(2-ethoxyethoxy) ethyl acrylate- co -7-(2-methacryloyloxyethoxy)-4-methylcoumarin) (PEEC) acrylic IOL materials were synthesized. The antiproliferative drug 5-fluorouracil (5-FU) could be chemically grafted to the PEEC IOL materials easily via a light induced [2 + 2] cycloaddition reaction with the coumarin group, getting drug-loaded IOL (PEEC@5-FU IOL). The PEEC@5-FU IOL exhibited excellent optical and mechanical properties and biocompatibility. More importantly, the loaded 5-FU could be easily controlled from release by light irradiation via photo-dissociation of the cyclobutane ring that was obtained by the [2 + 2] cycloaddition reaction of 5-FU and coumarin. The in vitro and in vivo experiments demonstrated that such photo-controllable drug release IOL could effectively prevent PCO after implantation in a safe way. [Display omitted] • The coumarin residue contained PEEC IOL materials were designed and synthesized. • The PEEC IOLs load 5-FU via light induced [2 + 2] cycloaddition reaction and release it in photo-controlled way. • The drug release profile can be tuned by the light irradiation parameters. • Photo-controllable drug releasing IOL are biocompatible and can inhibit HLEC proliferation after light irradiation. • Photo-controllable drug releasing IOL can inhibit PCO development on demand and have good in vivo safety. [ABSTRACT FROM AUTHOR]

Purpose: Hyperammonemia is a serious adverse effect of 5-fluorouracil (5FU) administration. Hemodialysis can be used for its management, but detailed data on the concentrations and removal rate of 5FU and its metabolites during hemodialysis remain unclear. Here, we present two cases of hemodialysis patients with end-stage renal disease who received concurrent 5FU infusion. Methods: Blood samples were collected from the hemodialysis circuit before and after the dialyzer during day 2 hemodialysis sessions, and from the internal shunt just before and after day 4 hemodialysis sessions. The serum levels of 5FU and its metabolites—α-fluoro-β-alanine (FBAL) and monofluoroacetate (FA)—were measured using liquid chromatography-tandem mass spectrometry. Results: Seven sets of blood samples were collected for case 1; the removal rates (mean ± standard deviation) of 5FU and FBAL by the dialyzer were 81.2 ± 23.2% and 96.1 ± 8.6%, respectively (p < 0.001). Three sets of blood samples were collected for case 2; the removal rates of 5FU and FBAL were 81.7 ± 3.9% and 94.8 ± 2.7%, respectively (p = 0.03). Twenty-seven sets of blood samples were collected for case 1; reductions in blood FBAL and FA levels were 49.3 ± 8.8% (p < 0.001) and 64.2 ± 30.3% (p = 0.04), respectively. Bayesian estimation yielded similar results. Three sets of blood samples were collected for case 2; reductions in the blood FBAL and FA levels were 49.9 ± 6.9% and 50.6 ± 33.0%, respectively. Conclusion: In this study, 5FU and its metabolite FBAL were directly removed from the blood by approximately 90% during hemodialysis, and the blood levels of FBAL and FA were reduced by approximately 50% with a single hemodialysis session. [ABSTRACT FROM AUTHOR]

The current study focuses on the preparation and optimization of lipid PLGA hybrid nanoparticles of 5-fluorouracil (5-FU-LPHNs) using a three-factor, three-level Box-Behnken design for sustained release and enhanced in-vitro anticancer efficacy. The morphology of the developed 5-FU-LPHNs was spherical and found in the range of 155.7–316.4 nm, entrapment efficiency (80%–92%), polydispersity index (0.11–0.19) and zeta potential (−19.7 mV to −29.4 mV) depicting nano-sized and stable nanoparticles. The XRD and DSC investigations showed the absence of characteristic peaks of 5-fluorouracil in the developed formulations indicating amorphization and successful encapsulation of 5-fluorouracil in the developed LPHNs. The in-vitro release showed a biphasic release pattern with an initial burst release pursued by sustained release up to 72 h. The in-vitro cytotoxicity studies of the developed 5-FU-LPHNs were found more cytotoxic than the free drug solution in HT-29 and HCT116 cancer cell lines. In both cell lines, the half maximal inhibitory concentration (IC50) values of 5-FU-LPHNs were approximately 2.06-fold and 1.83-fold, less than that of the 5-FU solution (p <.05). These results suggest that the developed LPHNs can be used as a potential drug delivery approach for the effective delivery of 5-fluorouracil with enhanced anticancer efficacy to colorectal tumors. [ABSTRACT FROM AUTHOR]

The study investigated the use of 5-fluorouracil-loaded ZnO nanocomposites (5-FU/Gd-ZnO NCs) as a potential treatment for cancer. 5-FU is a commonly used drug for cancer treatment but has undesirable side effects. The materials were characterized using various techniques, including PXRD, FTIR, FESEM, TEM, DLS, £-potential, and AFM. The data showed that the nanocomposites had a plate-like agglomeration with particle diameters ranging from 317.6 to 120.1 nm. The IC50 value of 5-FU-ZnO, which inhibits cell growth, was found to be 1.85 ppm. The effects of 5-FU-ZnO on inflammatory markers were also examined. While 5-FU increased the levels of TNF-a and IL-1b, the nanocomposites were able to reduce these levels. Additionally, the 5-FU/Gd-ZnO-NCs group showed an increase in thiol levels and a decrease in catalase and superoxide dismutase levels. Flow cytometry results showed that 5-FU, ZnO-NCs, and 5-FU/Gd-ZnO-NCs did not have any additive or synergistic effects on the suppression or eradication of cancer cells. In vivo, experiments showed that the 5-FU/Gd-ZnO NCs had similar necrotic characteristics and reduced fibrosis and collagen deposition compared to the free medication. The nanocomposites also exhibited higher antioxidative activity and lower inflammatory responses compared to the 5-FU group. It was shown that 5-FU/Gd-ZnO-NCs successfully inhibit cell proliferation. The in vivo results were comparable to those obtained with free 5-FU, suggesting the potential of these nanocomposites as therapeutic agents. [ABSTRACT FROM AUTHOR]

Mucositis is a high-incidence side effect in cancer patients undergoing chemotherapy. Next-generation probiotics are emerging as new therapeutic tools for managing various disorders. Studies have demonstrated the potential of Akkermansia muciniphila to increase the efficiency of anticancer treatment and to mitigate mucositis. Due to the beneficial effect of A. muciniphila on the host, we evaluated the dose–response, the microorganism viability, and the treatment protocol of A. muciniphila BAA-835 in a murine model of chemotherapy-induced mucositis. Female Balb/c mice were divided into groups that received either sterile 0.9% saline or A. muciniphila by gavage. Mucositis was induced using a single intraperitoneal injection of 5-fluorouracil. The animals were euthanized three days after the induction of mucositis, and tissue and blood were collected for analysis. Prevention of weight loss and small intestine shortening and reduction of neutrophil and eosinophil influx were observed when animals were pretreated with viable A. muciniphila at 1010 colony-forming units per mL (CFU/mL). The A. muciniphila improved mucosal damage by preserving tissue architecture and increasing villus height and goblet cell number. It also improved the integrity of the epithelial barrier, decreasing intestinal permeability and bacterial translocation. In addition, the treatment prevented the expansion of Enterobacteriaceae. The immunological parameters were also improved by decreasing the expression of pro-inflammatory cytokines (IL6, IL1β, and TNF) and increasing IL10. In conclusion, pretreatment with 1010 CFU/mL of viable A. muciniphila effectively controlled inflammation, protected the intestinal mucosa and the epithelial barrier, and prevented Enterobacteriaceae expansion in treated mice. [ABSTRACT FROM AUTHOR]

This original article presents the findings of a comprehensive case series, shedding light on the efficacy of diverse treatment modalities for managing precancerous and cancerous skin lesions and their remarkable rejuvenation effects on the skin. A particular focus is placed on the promising outcomes achieved through the application of a combination treatment involving 5-Fluorouracil (5-FU) and salicylic acid, which demonstrates enduring and noteworthy results. Furthermore, alternative therapeutic approaches, including 5-FU monotherapy, Methyl aminolevulinate–photodynamic therapy (MAL-PDT), and the combination of Imiquimod therapy with MAL-PDT, exhibit substantial potential for patients seeking non-surgical solutions. These treatments manifest as valuable tools in improving skin texture and mitigating the effects of photodamage. Nevertheless, the intricate interplay between the chosen treatment, the extent of photodamage, and individual patient characteristics, with a particular emphasis on age, necessitates long-term follow-up to gauge treatment outcomes and the likelihood of lesion recurrence. Notably, these treatments are associated with a significant degree of inflammation, igniting curiosity regarding enhanced skin cellular turnover and the potential for a more youthful skin appearance. Our findings accentuate the promise of topical fluorouracil (5-FU) and photodynamic therapy (PDT) in combating photoaging among patients with actinic keratoses. However, a need for further in-depth research is evident to unravel the nuanced relationships between these treatments, the severity of photodamage, and the influence of patient-specific factors. Such comprehensive investigations are instrumental in optimizing patient care and outcomes, offering a holistic approach to managing photodamage within the context of actinic keratoses. This work, when combined with existing literature, provides valuable insights and serves as a catalyst for future research to fully unlock the potential of these treatments, ultimately enhancing the quality of patient care. [ABSTRACT FROM AUTHOR]

Introduction: Seroma is a frequent complication that can affect the final result of reconstructive and cosmetic surgeries. Methodology: This study evaluated the effectiveness of 5-Fluorouracil and 75% hypertonic glucose in preventing seroma in a mastectomy rat model, as well as cellular and vascular events in adjacent tissues. A left mastectomy with lymphadenectomy was performed in 60 Wistar-Albino female rats. Animals randomly allocated to the control group (Group I; n = 20) were sutured right after mastectomy. The intervention groups received 1.0 mL of 75% hypertonic glucose (Group II; n = 20) or 1.0 mL of 5-Fluorouracil (Group III; n = 20) at the surgical site before suturing. The assessment of the presence of seroma was performed in all animals at 24, 48, and 72 h and on the 7th and 12th postoperative day. After the 12th day, a tissue sample was taken from the surgical site and sent for histological analysis. The occurrence of seroma was assessed using GEE. A significance level of 5% was adopted. Results: Differences in seroma formation over time were observed for both Control Group I (p=0.041) and Intervention Group II (p<0.001). In Intervention Group III, there was no difference in the percentage and volume of seroma across the assessment points (p=0.627). When both the Control and Intervention Group II were compared to Intervention Group III, we found a reduction in seroma formation in the last group. The reduction in the inflammatory process was more regular to Intervention Group III. Conclusion: In this animal model, 5-Fluorouracil was more effective in preventing seroma formation than 75% Hypertonic Glucose. No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Background: Capecitabine is an oral prodrug of the active metabolite 5-fluorouracil, which has been used effectively in human colorectal, head and neck, and mammary carcinomas. Capecitabine has several properties that make it an attractive treatment option for dogs: (i) it is relatively inexpensive, (ii) it has a short half-life in humans, allowing for rapid plasma concentration changes to be achieved with dosage adjustments, (iii) it is effective for treating carcinomas in humans, for which there are no widely-effective oral chemotherapy options in dogs, and (iv) it is thought to preferentially target cancer cells due to different expression of thymidine phosphorylase, thereby decreasing the risk of off-target side effects. However, capecitabine has not been widely explored as a chemotherapy agent for dogs. The goal of this study was to determine the plasma disposition of capecitabine in dogs following a single oral dose and to document any adverse events associated with capecitabine administration over the course of 5 weeks. Results: Capecitabine was well tolerated throughout the 5-week study period when administered to 5 dogs with naturally occurring carcinomas at 750 mg/m 2 by mouth once daily for 14 consecutive days in a 3-week cycle. No dogs withdrew from the study due to adverse events or other causes. The median AUC 0-last was 890 h · ng/ml (range 750-1100 h · ng/ml); however, the maximum blood concentration and time to reach that concentration of capecitabine was highly variable after a single dose. Conclusions: Capecitabine appears well-tolerated as an oral chemotherapy agent for dogs with carcinomas, although individualized dosing may be necessary, and further studies are warranted. [ABSTRACT FROM AUTHOR]

Bleomycin and 5-fluorouracil (5-FU) are widely used in various dermatological disorders. Both drugs are well-recognized as antineoplastic drugs and exert their effect by blocking the cell cycle. Topical and intralesional formulations are available and have been studied in both non-neoplastic and cancerous lesions. However, data comparing the effect of bleomycin and 5-FU in the dermatological disorders are limited. This review outlines the action mechanisms of both drugs and compares their clinical efficacies in a wide range of dermatologic diseases including hypertrophic scar, wart, skin cancer, vascular malformation, hemangioma, and vitiligo, and discusses the overall safety of the drugs. Intralesional bleomycin treatment is effective in hypertrophic scars and warts, but intralesional 5-FU may also be considered since it is cheaper and less painful. Moreover, intralesional 5-FU and bleomycin injection is a viable option for premalignant lesions (i.e., actinic keratosis) and inoperable skin cancers. Both bleomycin and 5-FU have been applied as treatment adjuncts for vitiligo, with 5-FU showing a slightly better outcome. Both agents have a good safety profile, and no serious side effects have been reported following their use in the field of dermatology. [ABSTRACT FROM AUTHOR]

Purpose: A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. Methods: Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and continuous infusion of 5‐fluorouracil (750 mg/m2 per day) on days 1–5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. Results: Twenty‐six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. Conclusion: Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution. [ABSTRACT FROM AUTHOR]

Hollow mesoporous silica nanoparticles (HMSNs) are promising drug carriers due to their large surface area, high porosity, and biocompatibility. In this study, a straightforward and adjustable synthesis strategy was developed for generating HMSNs with tunable hollow cavities and use them to deliver 5-fluorouracil, a common anticancer drug as model drug. This approach involves using solid SiO2 nanoparticles (sSiO2 NPs) and cetyltrimethylammonium bromide (CTAB) as templates. Remarkably, our study introduces the application of I-optimal design to optimize the size of sSiO2 NPs, subsequently impacting the internal cavity diameter and drug loading capacity of the resulting HMSNs. Dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Brunauer Emmett-Teller (BET) analysis, Fourier-transform infrared (FTIR) spectroscopy and in vitro drug release were conducted to characterize the synthesized particles. Moreover, the blood compatibility and cytotoxicity were performed to demonstrate the biocompatibility of as-synthesized HMSNs. Notably, the investigation unveils that both the internal cavity size and shell thickness have discernible effects on drug loading and release behavior. Furthermore, it was observed that HMSNs particle size played a significant role in their hemocompatibility, while confirming that all synthesized HMSNs exhibited appropriate biocompatibility. Overall, these findings highlight the facile control and manipulation of drug loading and release characteristics within HMSNs through tuning the hollow cores. Additionally, these results demonstrate the potential for regulating hemocompatibility, thereby expanding the range of applications for these nanoparticles. This research provides an innovative and versatile methodology for the synthesis of HMSNs, emphasizing their potential application in drug delivery systems. [ABSTRACT FROM AUTHOR]

Introduction: This case report demonstrates the possibility of successful eye and vision-sparing therapy for caruncular melanoma. Case Presentation: We present an atypical presentation of a caruncular melanoma. After excisional biopsy, residual flat conjunctival melanosis resolved using topical chemotherapy (5-fluorouracil), which was well tolerated. Relapse of the melanoma was treated with external beam radiotherapy, but the tumor grew despite treatment. Eighteen months after complete excision of the relapsed melanoma, the patient remains tumor-free while the eye and its function remain preserved. Conclusion: This case report suggests that aggressive eye-sparing therapy for caruncular melanoma combining surgery, adjuvant topical chemotherapy, and external beam radiotherapy, can be an alternative for primary orbital exenteration. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU) is one of the most broadly chemotherapeutic compounds employed in treating solid tumors. Quercetin (QU) as a flavonoid has diverse positive clinical applications including antioxidative, antiproliferative, and anti-inflammatory. The current study aims to assess the histopathological changes and anti-oxidative effects of QU loaded with chitosan nanoparticles (QU-NPs) on the testicular injury triggered by 5-FU in mice. Twenty male albino mice were randomly divided into 4 groups as follows: the control, 5-FU, 5-FU + QU (5 mg/kg), and 5-FU + QU-NPs (5 mg/kg) for 14 days. Oxidative marker [malondialdehyde (MDA)] and antioxidant markers [superoxide dismutase (SOD) and catalase (CAT)] were examined in serum. Testicular damage stemmed from a single dose injection of 5-FU intraperitoneally (i.p.). The control group received normal saline and the treatment groups received QU with i.p. injection for 14 days. Serum MDA level was lower in the QU and QU-NPs treated groups than in the 5-FU group. Moreover, serum CAT levels were remarkably increased in both the QU- and QU-NPs treated groups compared to the 5-FU group. In the case of SOD, the most considerable difference was found between the 5-FU group and the QU-NPs, but not the QU group. Further, both QU and QU-NPs, particularly the QU-NPs, ameliorated 5-FU-induced testicular tissue damage, as evidenced by a decrease in hyperemia, edema, and vacuolation, and an improvement in the area of seminiferous tubules, and spermatocyte and seminiferous tubule counts. Nanotechnology and fabrication of QU-NPs can ameliorate the testicular damage caused by 5-FU. [Display omitted] • 5-fluorouracil exposure could induce spermatogenesis disorder in mice. • 5-fluorouracil caused testicular and epididymal histopathological lesions in mice. • 5-fluorouracil decreased serum testosterone levels in mice. • Quercetin improves the oxidative damage induced by 5-FU. [ABSTRACT FROM AUTHOR]

Although astaxanthin (ASX) is one of the most studied antioxidant molecules, its curative effect against ovarian damage caused by 5-fluorouracil (5-FU) has not been demonstrated to date. It was therefore aimed to investigate whether ASX is therapeutic against 5-FU-induced ovotoxicity in this study. Rats were first exposed to 5-FU (100 mg/kg) and then treated ASX (250 µg/kg) for three days. Oxidative stress (OS), inflammation and apoptosis markers were determined using spectrophotometric methods. Ovarian tissues were also evaluated histologically. The levels of OS, inflammation and apoptosis biomarkers increased by 5-FU administration (p<0.05). Treatment with ASX significantly alleviated these markers (p<0.05). These findings reveal that ASX may exert an ovoprotective effect by reducing pro-inflammatory mediators and enhancing antioxidant status in ovarian tissue. [ABSTRACT FROM AUTHOR]

To fulfil the synergistic delivery and on-demand drug release of 5-fluorouracil (5-FU) and methotrexate (MTX) at tumor sites, we innovatively synthesized pH and redox responsive self-assembling nanoparticles based on ZIF-8 frameworks as the 5-FU vehicle decorated with hyaluronic acid-MTX bioconjugates linked with a redox-responsive disulfide bond. The constructed HA-SS-MTX/5-FU@ZIF-8 nanoplatform exhibited monodisperse and spherical shape with a mean hydrodynamic diameter of 161.0nm and loaded about 0.345 g of 5-FU and 0.0508 g of MTX per gram. The preliminary in vitro experiments showed that the as-prepared HA-SS-MTX/5-FU@ZIF-8 nanoparticles (NPs) displayed high inhibiting proliferation and promoting apoptosis performance towards the colon cancer cells. [ABSTRACT FROM AUTHOR]

In this study, the inclusion complexes of α-, β-cyclodextrins and derivatives hydroxypropyl-α-, hydroxypropyl-β-cyclodextrins with uracil and the anti-cancer agent 5- fluorouracil were demonstrated by UV-Vis spectroscopy and quantum chemical calculations. The complexes stability constants and the thermodynamic parameters for the 1:1 stoichiometry inclusion complexes were obtained and compared. The thermodynamic analysis of the studied complexes showed that the inclusion reaction is an exothermic spontaneous reaction and is an enthalpy driven process for the temperature domain of 298K to 313K. Theoretical calculations were performed on complexes to examine the energetic quantities involved in the stability of the complexes. The correlation of the energy parameters obtained from experimental and theoretical data suggests a high affinity between cyclodextrins and both uracil and 5-fluorouracil molecules. [ABSTRACT FROM AUTHOR]

5-Fluouracil (FU) is an anti-cancer drug, most commonly used to treat solid malignancies across the globe, and Naringenin (NG) is a natural flavonoid with antioxidant properties. The present study was conducted on rats, which were divided into four groups to estimate the ameliorative effect of NG (100 mg/kg BW/day for 28 days- Group-3) against 5-FU-induced pulmonary toxicity (20 mg/kg BW/day- Group-2 for first 5 days). Group-1 rats were treated with normal saline, whereas group-4 rats were treated with the combination of both NG + 5-FU with same above protocol. During the subsequent period, six rats were sacrificed from each group on the 14th and 28th day of the experiment. Lung tissues were collected for various analyses like antioxidants profile, cytokine profile, histopathology, immunohistochemical and ultrastructure pathology. 5-FU-induced toxicity was characterized by a significant (p<0.05) increase in TBARS in group 2, along with a significant (p<0.05) reduction in GSH and SOD concentration on the 14th and 28th day of the experiment. Whereas, the combination group showed a significant decrease in thiobarbituric acid reactive substrate (TBARS) and increased GSH and SOD levels. Further, a significant (p<0.05) increase in pro-inflammatory cytokines (TNF-α, IL-6, TGF-β and IL-1β) along with a considerable (p<0.05) lower level of IL-10 was observed in group 2 rats and significant improvement in all the parameters were observed in group-4 rats. In addition, on histopathological examination (HP), severe lung damage was observed along with oedema and mild fibrous tissue proliferation were noted which was further supported by scanning electron microscopy. Immunostaining of lung sections revealed strong positivity for NF-κB, COX-2 and TNF-α expressions. However, treatment with NG exhibited a moderate decrease in the intensity of tissue damage observed in group 4 rats compared to group 2 rats. Overall, the intensity of toxicity was more evident on 28th day than 14th day in group 2 rats and a notable improvement in NG treatment of group-4 rats. Based on results, we suggested that NG had protective effects in ameliorating 5-FU-induced pulmonary toxicity. [ABSTRACT FROM AUTHOR]

Patients with advanced liver cancer may benefit from 5‐fluorouracil (5‐FU) therapy. However, most of them eventually faced drug resistance, resulting in a poor prognosis. The present study aims to explore the potential mechanism of let‐7g/ABCC10 axis in the regulation of 5‐FU resistance in liver cancer cells. Huh‐7 cells were used to construct 5‐FU resistant Huh‐7/4X cells. CCK8, flow cytometry, and TUNEL staining were used to detect the characterization of Huh‐7 cells and Huh‐7/4X cells. Double luciferase report, PCR, and western blot analyses were used to detect the regulatory effects between let‐7g and ABCC10. The levels of biomarkers related to cell cycle progression and apoptosis were detected by western blot assays. The role of let‐7g in 5‐FU sensitivity of liver cancer cells was evaluated in nude mice. Compared with LX‐2 cells, the expression of let‐7g was decreased in Hep3B, HepG2, Huh‐7, and SK‐Hep1 cells, with the lowest expression in Huh‐7 cells. The sensitivity of Huh‐7 cell to 5‐FU was positively correlated with let‐7g expression. Transfection of let‐7g mimics inhibited the viability of Huh‐7/4X cells by prolonging the G1 phase, with the downregulation of ABCC10, PCNA, Cyclin D1, and CDK4. Meanwhile, let‐7g promoted apoptosis to increase 5‐FU sensitivity of Huh‐7/4X by downregulating ABCC10, Bcl‐XL as well as upregulating Bax, C‐caspase 3, and C‐PARP. Dual‐luciferase assay further confirmed that let‐7g inhibited ABCC10 expression by binding to the ABCC10 3'‐UTR region. Furthermore, let‐7g increased the sensitivity of Huh‐7/4X to 5‐FU in vitro and in vivo, which can be reversed by ABCC10 overexpression. In conclusion, let‐7g sensitized liver cancer cells to 5‐FU by downregulating ABCC10 expression. [ABSTRACT FROM AUTHOR]

This work presents the synthesis and characterization of a composite made of superparamagnetic iron oxide and hydroxyapatite nanoparticles (SPION/HAp) with a well-developed surface for loading anticancer drugs and for use in magnetic hyperthermia and local chemotherapy. The proposed material was obtained by an easy one-pot co-precipitation method with a controlled ratio of SPION to HAp. The morphology was studied by SEM and TEM, indicating rod-like structures for high HAp content in the composite and granule-like structures with increasing SPION. Its crystallinity, elemental composition, and functional groups were determined by X-ray diffraction, EDS, and FT-IR, respectively. The nanocomposite was then stabilized with citrates (CA), polyethylene glycol (PEG), and folic acid (FA) as agents to improve intracellular absorption, while turbidimetric studies confirmed that only citrates effectively stabilized the magnetic carriers to form a colloidal suspension. Subsequently, 5-fluorouracil (5-FU) was loaded into the magnetic carriers and tested in vitro using the L-929 cell line. The studies showed no cytotoxicity of the citrate-stabilized suspension against fibroblasts and some cytotoxicity after 5-FU release. In addition to in vitro studies, the composite was also tested on biomimetic membranes made of DOPC, DOPE, cholesterol, and DOPS lipids using Langmuir trough. The results show that the resulting suspension interacts with biomimetic membranes, while magnetic hyperthermia studies confirm effective heat generation to achieve therapeutic 42–46 °C and improve drug release from magnetic carriers. [ABSTRACT FROM AUTHOR]

Injury to the skin can cause abnormal wound healing and continuous inflammation that leads to the formation of hypertrophic scars and keloids. These lesions often cause significant negative impact on a patient's life due to aesthetic, physical, social, and psychological consequences. Numerous treatment modalities exist for these hypertrophic scars and keloids, which include silicone sheeting, pressure garments, intralesional injection/topical application of scar-modulating agents, laser therapy, and surgical excision. Due to increased efficacy, an evolving treatment paradigm encourages the use of multiple treatment modalities instead of one treatment modality. However, no gold standard treatment exists for these lesions, leaving many people with unsatisfactory results. Adding scar-modulating agents such as 5-Fluorouracil, bleomycin, or Botulinum Toxin A to triamcinolone monotherapy has emerged as a potential drug combination for treating hypertrophic scars and keloids. We sought to critically analyze the evidence that exists for the use of more than one scar-modulating agent. This was done by conducting a systematic review to determine the efficacy of these combined drug regimens. We found that many of these combinations show evidence of increased efficacy and fewer/similar adverse events to triamcinolone monotherapy. Triamcinolone and 5-Fluorouracil showed the strongest and most consistent evidence out of all combinations. With this review, we intend to encourage more research into unique drug combinations that may improve outcomes for patients with symptomatic hypertrophic scars or keloids. [ABSTRACT FROM AUTHOR]

This research aimed to investigate whether melatonin affected sensitivity to 5‐fluorouracil (5‐FU) in colorectal cancer (CRC) as well as to show the underlying molecular mechanism. Melatonin and 5‐FU were added to CRC cells at varying doses. The effect of melatonin on sensitivity to 5‐FU was investigated by measuring cell activity and apoptosis, and the potential underlying mechanism was further explored by detecting miR‐532‐3p expression and the associated pathway proteins. Melatonin could suppress cell malignancy in SW480 and HCT116 cells. Melatonin also significantly promoted sensitivity to 5‐FU in CRC cells. miR‐532‐3p expression was downregulated in CRC and was also markedly enhanced when treated with 1 mmol/L melatonin. The inhibitory ability of the co‐cultured melatonin, 5‐FU, and miR‐532‐3p inhibitor on SW480 and HCT116 cells was markedly diminished, and the IC50 value was significantly enhanced. Relative to the melatonin group, melatonin+miR‐532‐3p inhibitor markedly declined apoptosis rate. Bioinformatics analysis predicted the target of miR‐532‐3p. β‐catenin level presented obvious downregulation in the melatonin group, while it was notably upregulated in the co‐culture group in relative to with that in the melatonin group. Overall, melatonin promotes sensitivity to 5‐FU in CRC cells by regulating the miR‐532‐3p/β‐catenin pathway. [ABSTRACT FROM AUTHOR]

Copyright of Osmangazi Journal of Medicine / Osmangazi Tip Dergisi is the property of Eskisehir Osmangazi University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Sichuan University (Medical Science Edition) is the property of Editorial Board of Journal of Sichuan University (Medical Sciences) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Objectives: Urethral strictures are the most common complications after surgical treatments of benign prostatic hyperplasia (BPH). Despite various preventive measures, the search for medications with antiproliferative activity and the development of surgical procedures to prevent the development of urethral strictures are still relevant. We evaluated the preventive efficacy of 5-fluorouracil against urethral strictures in patients undergoing surgery for BPH. Materials and Methods: A non-randomized clinical trial including 246 male patients with an average age of 70.0 ± 8.0 years was conducted. The main study group included 124 patients who, in addition to the standard treatment, received lavage with a 5-fluorouracil solution (1000 mg/20 mL per 500 mL of 0.9% isotonic saline) using a modified three-way urethral catheter. The monitoring of clinical, laboratory, and instrumental parameters was carried out 10 days, 3 months, and 6 months after surgery. Results: The evaluation of severity for dysuria symptoms in patients using the IPSS scale throughout the entire follow-up period showed a statistically significant decrease in ischuria and stranguria, prolongation of the interval between urinations, a decrease in intermittent urination, urinary incontinence, and straining before urination in the main group in comparison with the control patients. The patients of both study groups noted an improvement in the quality of life. It was found statistically significant decrease in the maximum urinary flow rate in the main group (p < 0.001). In the control group, after three months, four cases of urethral strictures and stenosis were recorded; after six months, this rate reached nine cases (7.3%), while in the main group, only one patient with infravesical obstruction was found (0.8%) (χ2 = 3.855, p < 0.05). Conclusions: The results of our study could indicate the effectiveness of the antiproliferative drug 5-fluorouracil in combination with use of a modified catheter in relation to the development of postoperative urethral strictures. [ABSTRACT FROM AUTHOR]

The possible protective effect of sitagliptin (SIT) against nephrotoxicity induced by a single dose 5-fluorouracil (5-FU) (150 mg/kg, i.p.) was investigated in rats. SIT treatment (5 and 10 mg/kg/day, p.o.) was given for 7 days, starting 5 days before 5-FU administration. Both SIT doses caused significant reductions of serum creatinine and neutrophil gelatinase-associated lipocalin levels in rats received 5-FU. Both doses of SIT also significantly decreased malondialdehyde, tumor necrosis factor-α, interleukin-1β, nuclear factor-κB p65 (NF-κB p65), Bax/Bcl-2 ratio, and cleaved caspase-3 in kidneys of 5-FU-challenged rats. Additionally, SIT, at both doses, significantly increased renal total antioxidant capacity and nuclear factor erythroid 2related factor 2 (Nrf2) in rats received 5-FU. Besides, SIT markedly attenuated the 5-FU-induced histopathological kidney tissue injury in rats. It was concluded that SIT, at both doses, provided a significant nephroprotective effect in 5-FU-challenged rats, through its antioxidant, antiinflammatory, and antiapoptotic activities, and by modulating Nrf2 and NF-κB pathways. [ABSTRACT FROM AUTHOR]

Aim and background: In this research, we aimed to compare the nasal adhesion prevention after combined endoscopic partial inferior turbinectomy and submucous resection of the nasal septum between 5-fluorouracil and silastic. Patients and methods: 50 individuals with persistent nasal obstruction brought on by hypertrophy of the inferior turbinates and a deviated nasal septum who had not responded to medical therapy were the subject of this investigation. With a mean age of 25, they ranged in age from 16 to 56. 26 patients were men and 24 were women. 25 of these patients were placed in group A (the fluorouracil group), and 25 were placed in group B. (silastic group). Results: Regarding preoperative data, there was no statistically significant difference between the two groups. Conclusion: Our data and statistical analysis revealed that 5-FU application during endoscopic partial inferior turbinectomy combined with submucous resection of the nasal septum is an easy, effective, and safe method in reducing and preventing formation of adhesions as silastic sheet with a significantly lower postoperative pain, headache, and nasal obstruction than silastic in the first week postoperative. [ABSTRACT FROM AUTHOR]

Background: The tumor microenvironment clearly influences cancer progressing properties but less is known about how individual cancer microenvironments potentially moderate cancer treatment effects. By cultivating and treating cancer cell lines in patient-derived scaffolds (PDS), the impact of specific characteristics of individual cancer microenvironments can be incorporated in human-like growth modelling and cancer drug treatment testing. Methods: PDSs from 78 biobanked primary breast cancer samples with known patient outcomes, were prepared and repopulated with donor breast cancer cell lines, followed by treatment with 5-fluorouracil or doxorubicin after cellular adaption to the various microenvironments. Cancer cell responses to the treatments were monitored by RNA-analyses, highlighting changes in gene sets representative for crucial tumor biological processes such as proliferation, cancer stem cell features, differentiation and epithelial-to-mesenchymal transition. Results: The chemotherapy treatments induced distinct gene expression patterns in adapted cancer cells with clusters of similar treatment responses depending on the patient-derived cancer microenvironment used as growth substrate. The doxorubicin treatment displayed a favorable gene signature among surviving cancer cells with low proliferation (MKI67) and pluripotency features (NANOG, POU5F1), in comparison to 5-fluorouracil showing low proliferation but increased pluripotency. Specific gene changes monitored post-treatment were also significantly correlated with clinical data, including histological grade (NANOG), lymph node metastasis (SLUG) and disease-free patient survival (CD44). Conclusions: This laboratory-based treatment study using patient-derived scaffolds repopulated with cancer cell lines, clearly illustrates that the human cancer microenvironment influences chemotherapy responses. The differences in treatment responses defined by scaffold-cultures have potential prognostic and treatment predictive values. [ABSTRACT FROM AUTHOR]

Background: 5-FU has multiple applications in various cancers but has limitations owing to its shorter half-life and rapid metabolism. In this study, injectable intratumoral gels were developed to enhance 5-FU concentrations in tumor vicinity. Sterile tunable poly (N-isopropylacrylamide)-based pH/thermo dual-sensitive self-assembled and in situ crosslinkable injectable depot gels with low viscous grade of chitosan (LVCS) were developed via cold and free radical polymerization method for localized and sustained delivery. Results: Rheological analysis confirmed the gelation temperature, sol–gel transitions and viscoelastic behavior of in situ gels. Swelling–deswelling–reswelling cycles established the effect of temperature on structural changes. Swelling tests and in vitro drug release conducted in various dissolution media at variable temperatures confirmed pH/thermal dual response of formulations. Methyl thiazolyl tetrazolium assay confirmed that the hydrogels have good cytocompatibility with above 85% cells viability in Vero cells. In vitro cytotoxicity assay against MCF-7 cells displayed that 5-fluorouracil has good anticancer activity in loaded gel form as compared to free 5-FU. The cytotoxic studies showed that IPLVCS-2 and IPLVCS-6 have the highest inhibition (IC50 = 47 ± 1 µg/ml, 34 ± 17 µg/ml) as compared to free 5-FU (IC50 = 52 ± 3 µg/ml). Conclusion: Current findings conclude that taking the advantage of physiologic environment acidic pH and high temperature of cancer cells, poly(NIPAAm)-g-LVCS formulations can effectively be used as intratumoral controlled depot of 5-FU. [ABSTRACT FROM AUTHOR]

Molecularly imprinted polymers and non‐imprinted polymers based on attapulgite and graphene composite were synthesized by coating with copolymer of acrylamide and methyl methacrylate. The adsorption results showed that the molecularly imprinted polymers and non‐imprinted polymers could reach the maximum drug loading of 2.4 and 1.6 mg/g, respectively. The in vitro release studies demonstrated that molecularly imprinted polymers and non‐imprinted polymers can control the release of 5‐fluorouracil and reach maximum release at approximately 48 h. Cytotoxicity analysis showed that 100 μg/mL of molecularly imprinted polymers loaded with 5‐fluorouracil gradually increased the inhibition rate of HeLa with increasing time and approached the maximum inhibition rate of 20 % at 72 h. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death worldwide, accounting for about 10 million deaths a year, or nearly one in six deaths. The most common types of cancer are breast, colorectal, lung, and prostate cancers. Prolonged application of hormone drugs leads to the development of resistance. The development of agents with high activity against resistant cells is a challenge. It is important to create novel targeted compounds and search for active molecules among those previously developed. The study aimed to evaluate the sensitivity of 4-hydroxytamoxifen-resistant cells to 5-fluorouracil (5-FU) and analyse the signalling pathways that are regulated by 5-FU in breast cancer cells. Antiproliferative activity of compounds was assessed by the MTT assay, and immunoblotting was used to evaluate the expression of proteins in breast cancer cells. Activity of 5-FU was evaluated on parental MCF7 cells and a cell subline with resistance to 4-hydroxytamoxifen (HT), named MCF7/HT. The MCF7/HT cells showed high sensitivity to 5-FU. Expression of oestrogen receptor α (ERα, a key driver of breast cancer growth) in MCF7 and MCF7/HT cells was not sensitive to 5-FU treatment. In both parental and resistant cells, 5-FU induced changes in the activity of several signalling proteins. 5-FU activated AKT, extracellular signal-regulated kinase 1/2 (ERK 1/2) and upregulated cyclin D1 expression. The data suggest that 5-FU should be further investigated as a chemotherapeutic for hormone-resistant cancers; the combination of 5-FU with novel apoptosis inducer LCTA-3344 is considered effective to inhibit the growth of breast cancer cells, including those that are hormone-resistant. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the deadliest malignancy in the world. The first-line chemotherapy used for CRC is 5-fluorouracil (5-FU). 5-FU completely eradicates rapidly proliferating and terminally differentiated tumor cells but fails to target cancer stem cells (CSCs). As a result, the tumor may shrink temporarily, but remnant CSC multiplies and forms a tumor again more aggressively. The recurrence and resistance lead to metastasis. Methodology: CRC was induced in 12 Sprague–Dawley (RPCP/IAEC/2019-20/R2) rats by 1,2 dimethyl hydrazine. Later, animals were treated with 5-FU for 7 weeks at a 10 mg/kg dose by the subcutaneous route. At the end of treatment, half population was sacrificed (6), whereas the remaining half (6) was left without treatment of 5-FU for 5 weeks and then sacrificed. Parameters such as body weight, complete blood count (CBC), immune cell subset (CD4, CD8, and NK cells), colon length to weight index, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) level, occult blood in stool, tumor multiplicity, and liver metastasis were estimated. In addition, the dissected colon was fixed in formalin and sent to the histology lab for hematoxylin-eosin staining and immunohistochemistry at both intervals. Results: All blood and tissue-based markers have shown significant differences (p < 0.05) between the animals sacrificed at the end of the 27th week and the end of the 32nd week for 5-FU treatment. Conclusion: It can be concluded that 5-FU up-regulates inflammatory cytokines and cell surface markers of CSC that promote CRC stemness via the Wnt/β-catenin pathway. Also, involvement of Nf-κB, fibronectin, MMP-9, and RANKL leads to tumorigenesis, disease aggressiveness, metastasis, and resistance. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy doses are usually prescribed on the basis of body surface area but dose banding is emerging as an efficient alternative. Dose banding presents the possibility of in-advance preparation in a Centralized Intravenous Admixture Service. Aim of the study: To evaluate the long-term stability of 5-fluorouracil at banded doses (700 mg and 800 mg) in polyolefin bags. Materials and methods: Ten polyolefin bags were prepared under aseptic conditions and stored at 23 ± 2°C for 24 days. Five of them were composed of 14 mL 5-fluorocuracil (700 g) in 100 mL 0.9% sodium chloride solution and the five other of 16 mL 5-fluorouracil (800 mg) in 100 mL 0.9% sodium chloride solution. At defined times, physical stability parameters were assessed: optical densities, pH measurements, visual and microscopical inspections. Solutions concentrations were measured using high-performance liquid chromatography coupled with a photodiode array detector. Results: No change was observed on pH and optical density measurements during the study period. Visual and microscopical inspections remained free of colour change, precipitate, microagregate or crystal. The concentrations of 5-Fluorouracil in 800 mg bags remained stable for 24 days while the concentration in 700 mg bags showed a stability of at least 17 days. Conclusion: Five-fluorouracil at banded doses of 700 and 800 mg in polyolefin bags is physicochemically stable for at least 17 days at 23 ± 2°C. These results support the possibility of in advance centralised preparation. [ABSTRACT FROM AUTHOR]

The combination of imaging contrast media and treatment strategies in one nanosystem has received great attention for cancer detection and treatment. This study aimed to develop Au@MnO/PEG/5FU (AMP/5FU) nanoparticles (NPs) for dual-modal CT/MRI and 5-Fluorouracil (5FU) anticancer drug delivery. The NPs showed a high 5FU loading capacity (90%), pH-responsive release profile, considerable X-ray attenuation, and MRI r1 relaxivity of 4.36 mM−1s−1. They had a significant toxic impact against A549 cancer cells that was greater than that of free 5FU. AMP/5FU NPs can be considered as a high potential multifunctional nanosystem for dual-modal CT/MRI and pH-responsive 5FU delivery. [ABSTRACT FROM AUTHOR]

The interaction of a PEGylated and non-PEGylated Fe3O4 nanoparticle drug-delivery system, with 5-fluorouracil (5-FU) as the chemotherapy drug, is investigated via atomistic molecular dynamics (MD). The induced pore formation in a dipalmitoylphosphatidylcholine (DPPC) bilayer phospholipid (BLPL) is studied, and the resulting hourglass-shaped pores with hydrophilic lipid headgroups lining the pores are observed. Furthermore, we optimize the required number of ligands that are required to allow for the formed pores to spontaneously reseal. Additionally, the number of water molecules that transverse through the water bridge is investigated. These results may be useful to design nanocarrier systems that will maintain the cellular osmotic pressure and stability, while the 5-FU is converted to the required metabolites inside the cell to serve its purpose as a chemotherapeutic drug. [ABSTRACT FROM AUTHOR]

Today, the disease treatment aims to increase the patient's quality of life, reduce the dose of drugs used, extend the dosing interval, and purify the patient from the side and harmful effects. Controlled drug release systems are the systems that respond best in this respect. In this study, the evaluation of the in vitro release of 5-fluorouracil for the transdermal delivery system of NaAlg/HPMC/TiO2 biocompatible membranes was investigated. The nanocomposite membrane was prepared by adding TiO2 nanoparticles to a mixture of sodium alginate and hydroxypropyl methylcellulose polymers. Membranes were analyzed by Fourier Transform Infrared, Scanning Electron Microscopy, Differential Scanning Calorimetry, X-Ray Diffraction, and Thermogravimetric analyses. In addition, water contact angles and mechanical tests of the membranes were carried out. The degree of swelling of the prepared membranes was examined; the highest swelling degree was obtained as 304.9% in pH 5.0 buffer. The effects of crosslinking time, nanoparticle amount, and temperature were investigated in the release studies of 5-FU. The highest drug release was found to be 65.3% at the end of 24 h in membranes containing 5% TiO2 and crosslinked for 1 h. The release kinetics of 5-FU were evaluated according to four kinetic models, and the release from NaAlg/HPMC/TiO2 membranes showed conformity with the Korsmeyer–Pappes model. [ABSTRACT FROM AUTHOR]

Over the past 50 years, 5-fluorouracil (5-FU) has played a critical role in the systemic chemotherapy of cancer patients. Bolus intravenous (IV) 5-FU infusion has been used due to the limitation of its extremely short half-life (10–15 min). This study used ultrasound (US) mediating 5-FU-loaded microbubbles (MBs) cavitation as a tool to increase local intratumoral 5-FU levels with a reduced dose of 5-FU (a single IV injection of 2.5 mg/kg instead of a single intraperitoneal injection of 25–200 mg/kg as used in previous studies in mice). The 5-FU-MBs were prepared with a 132 mg/mL albumin solution and a 0.30 mg/mL 5-FU solution. The diameters of the MBs and 5-FU-MBs were 1.24 ± 0.85 and 2.00 ± 0.53 µm (mean ± SEM), respectively, and the maximum loading efficiency of 5-FU on MBs was 19.04 ± 0.25%. In the in vitro study, the cell viabilities of 5-FU and 5-FU-MBs did not differ significantly, but compared with the 5-FU-MBs treatment-alone group, cell toxicity increased to 31% in the 5-FU-MBs + US group (p < 0.001). The biodistribution results indicated that the 5-FU levels of the tumors in small animals were significant higher for the 5-FU-MBs + US treatment than for either the 5-FU-MBs or 5-FU treatment with low 5-FU systemic treatment doses (2.5 mg/kg 5-FU IV). In small-animal treatment, 2.5 mg/kg 5-FU therapeutic IV doses injected into mice caused a more-significant reduction in tumor growth in the 5-FU-MBs + US group (65.9%) than in the control group after 34 days of treatment. [ABSTRACT FROM AUTHOR]

Insensitivity and resistance to 5-fluorouracil (5FU) remain as major hurdles for effective and durable 5FU-based chemotherapy in colorectal cancer (CRC) patients. In this study, we identified prostaglandin E synthase (PTGES)/prostaglandin E2 (PGE2) axis as an important regulator for 5FU sensitivity in CRC cells. We found that PTGES expression and PGE2 production are elevated in CRC cells in comparison to normal colorectal epithelial cells. Depletion of PTGES significantly enhanced the inhibitory effect of 5FU on CRC cell viability that was fully reverted by exogenous supplement of PGE2. Inhibition of PTGES enzymatic function, by either inducing loss-of-function mutant or treatment with selective inhibitors, phenocopied the PTGES depletion in terms of 5FU sensitization. Mechanistically, PTGES/PGE2 axis modulates glycolysis in CRC cells, thereby regulating the 5FU sensitivity. Importantly, high PTGES expression is correlated with poor prognosis in 5FU-treated CRC patients. Thus, our study defines PTGES/PGE2 axis as a novel therapeutic target for enhancing the efficacy of 5FU-based chemotherapy in CRC. [ABSTRACT FROM AUTHOR]

Aim: The OPTIM1SE study observed long‐term real‐world outcomes of cetuximab‐based infusional 5‐fluorouracil (5‐FU) regimens for first‐line treatment of metastatic colorectal cancer (mCRC) across Asia‐Pacific and Middle East regions, aiming to characterize their use, effectiveness, and safety in routine practice. Methods: OPTIM1SE was a prospective, open‐label, observational study. Patients with untreated KRAS wild‐type mCRC and distant metastases were treated per locally approved labels and monitored for 3 years via electronic medical records. The primary endpoint was the overall response rate (ORR). Secondary endpoints included safety, progression‐free survival (PFS), and overall survival (OS). Results: From November 19, 2013, to June 30, 2016, 520 patients were enrolled in 51 sites. Patients were mostly male (61.2%), with a mean age of 58.5 (±12.0) years; 420 patients received leucovorin, 5‐FU, and irinotecan–based regimens and 94 received leucovorin, 5‐FU, and oxaliplatin. The most common primary tumor site was the rectum (38.8%), with liver metastases (65.0%). ORR was 45.4% (95% CI, 41.1%–49.7%), including 26 patients (5.0%) with a complete response. Median PFS was 9.9 months (95% CI, 8.2–11.0); median OS (mOS) was 30.8 months (95% CI, 27.9–33.6). Higher mOS was associated with tumors of left compared with right‐sided origin (hazard ratio, 0.69 [95% CI, 0.49–0.99]); higher ORR was also associated with liver metastases compared with all other metastases (55.4% vs. 40.2%). Adverse events were consistent with the known safety profile of cetuximab. Conclusion: Cetuximab‐based 5‐FU regimens were effective first‐line treatments for mCRC in routine practice, particularly in patients with left‐sided disease and liver metastases only. [ABSTRACT FROM AUTHOR]

Drug resistance is a considerable obstacle to gastric cancer (GC) treatment. The current work aimed to elucidate the functional mechanism of CD109 in 5‐fluorouracil (5‐FU) resistance in GC. In this study, we demonstrated that CD109 was extremely heightened in 5‐FU‐resistant GC cells. CD109 deficiency lessened the IC50 value, impaired cell viability and metastatic capability, and induced cell apoptosis after 5‐FU treatment in cells. In addition, we found that PAX5 bound p300 increased the enrichment of H3K27ac at the promoter region of the CD109 gene, which resulted in the upregulation of CD109 in GC. Moreover, we also revealed that CD109 triggered 5‐FU resistance via activating the JNK/MAPK signaling. Blockage of JNK/MAPK signaling using JNK inhibitor, SP600125, abolished CD109 upregulation‐induced changes of IC50 values, cell viability, metastasis and apoptosis in NCI‐N87/5‐FU and SNU‐1/5‐FU cells. Importantly, CD109 silencing enhanced the therapeutic efficacy of 5‐FU, leading to reduced tumor growth in vivo. In conclusion, our results unveiled that H3K27 acetylation activated‐CD109 enhanced 5‐FU resistance of GC cells via modulating the JNK/MAPK signaling pathway, which might provide an attractive therapeutic target for GC. [ABSTRACT FROM AUTHOR]

Summary: To date, the clinical appearance and histological features of multiple minute digitate hyperkeratosis have been well characterized. However, there is no consensus on its treatment. After a comprehensive search of the databases MEDLINE, EMBASE, Web of Science, and the Cochrane Library and Database of Systematic Reviews, we have summarized the available clinical evidence regarding the therapeutic approaches already reported for this entity since its first description in 1967. Additional publications were identified within the references of retrieved papers. Sixty‐five articles have been revised, resulting in a total of 73 compatible cases. The histopathological features and different classifications used through history have also been considered, updating and completing the available knowledge. Ultimately, we propose topical treatment with 5 % 5‐fluorouracil formulated with 10 % salicylic acid as a potential treatment that has been used successfully in a 51‐year‐old woman at our facility. Further research in form of prospective or comparative studies is encouraged for a better conceptualization of the therapeutics of this disease. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Implementing the Quality by Design (QbD) approach enables pharmaceutical researchers to effectively reduce the number of experimental tests conducted and the associated time required. This aids in identifying important factors that substantially influence the quality of the goods, including vital material characteristics, formulation factors, and crucial procedure factors. This study aims to integrate the advantageous characteristics of Lipid Nanoparticles (LNPs) and the QbD approach to create an innovative Drug Delivery System (DDS) for treating skin cancers and actinic keratosis. LNPs, known for their high efficacy in the topical treatment of skin diseases, were formulated to address the skin layer's intricate structure and facilitate enhanced absorption. The present investigation employed the QbD methodology to fabricate LNP formulations to enhance the dermal permeation of 5-Fluorouracil (5-FU), a commonly utilized agent for treating non-melanoma skin cancer. The Lipid Nanoparticles containing 5-Fluorouracil (5-FLLNP) were synthesized using the Double Emulsion - Solvent Evaporation (DE-SE) technique. The DE-SE involves a dual-stage procedure encompassing two distinct emulsification steps, thereby introducing a heightened level of complexity to the overall process. The stability of nanoparticles produced through a DE-SE method is uncertain due to the various formulations and process attributes involved. Using a DE-SE technique in producing 5- FLLNP is a viable method for DDS, offering a means to achieve a highquality product through implementing the QbD approach. Artificial Neural Networks (ANN) have successfully developed an optimal LNP formulation that ensures quality and falls within the designated Design Space (DS). 5- FLLNP formulation exhibited a greater cell viability of 73% compared to the pure 5-FU formulation, which had a cell viability of 68% for A431 cells. [ABSTRACT FROM AUTHOR]

Background: Single-target inhibitors have not been successful in cancer treatment due to the development of drug resistance. Nevertheless, therapeutic agents capable of simultaneously inhibiting multiple targets have revealed encouraging results in inducing apoptosis and overcoming drug resistance in cancerous cells. Here, we designed a composite liposomal nano-carrier co-loading 5-Fluorouracil (5-FU) with all-trans retinoic acid (ATRA) to assess anticancer efficacy of the combined drugs in colorectal cancer (CRC). Methods: A PEGylated liposomal nano-carrier with phospholipid/cholesterol/DSPE-PEG (2000) was synthesized by the thin film hydration technique for co-delivery of ATRA and 5-FU. After characterizing, the role of 5-FU and ATRA co-loaded liposomal nano-carrier in proliferation, epithelial-mesenchymal transition (EMT), apoptosis, and cancer stem cells (CSCs) were investigated by using colony forming and MTT assay, RT-qPCR and Annexin V/PI kit. Results: The average size of liposomes (LPs) was < 150 nm with uniform size distribution. Drug release analyses indicated that both ATRA and 5-FU could simultaneously release from LPs in a sustained release manner. The synergistic inhibitory effects of ATRA and 5-FU loaded in LPs were verified with a combination index of 0.43. Dual drug LPs showed the highest cytotoxicity, enhanced inhibition of cell proliferation, increased apoptotic potential, decreased CSCs, and attenuated EMT-associated biomarkers. Also, dual drug LPs decreased β-catenin gene expression more than other liposomal formulations. Conclusion: These findings suggest that using LPs to achieve a synergistic effect of ATRA and 5-FU is an effectual approach to increase the therapeutic effect of 5-FU toward CRC cells. [ABSTRACT FROM AUTHOR]

Background Cardiogenic shock is a rare adverse event of 5-fluorouracil (5-FU) administration. Because of its rare entity, little is known about epidemiologic and clinical features of 5-FU-induced cardiogenic shock, and recommendations about specific treatment are missing. Case summary We present a case of cardiogenic shock and ventricular arrhythmia due to 5-FU-induced toxic cardiomyopathy treated with vasopressor and inotropic drugs in combination with intra-aortic balloon pump. Because of persistent haemodynamic instability, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella were implanted as a bridge to recovery. Systolic function recovered completely and the patient was weaned successfully. Discussion This case demonstrates toxic cardiomyopathy as a rare and potentially lethal cardiac adverse event of 5-FU administration. This case emphasizes the importance of mechanical support as bridging therapy to recovery of cardiac function. [ABSTRACT FROM AUTHOR]

L-arginine can produce nitric oxide (NO) under the action of inducible nitric oxide synthase (iNOS), while 5-fluorouracil (5-FU) can induce the increase of iNOS expression. The present study was to investigate the mechanism of L-arginine combined with 5-FU regulating glucose metabolism of hepatocellular carcinoma (HCC) through iNOS/NO/AKT pathway. The combination of L-arginine and 5-FU resulted in decreased cell survival and exhibited synergistic cytotoxic effects in HepG2 and SMMC7721 cells. Meanwhile, L-arginine increased 5-FU inhibitory effect on HepG2 and SMMC7721 cells by increasing NO production. Co-treatment with L-arginine and 5-FU resulted in a significant decrease in both G6PDH and LDH enzymatic activities, as well as reduced levels of ATP and LD compared to treatment with L-arginine or 5-FU alone. Moreover, the combination of L-arginine and 5-FU resulted in a decrease in the expression of GLUT1, PKM2, LDHA, p-PI3K and p-AKT. Furthermore, the combination demonstrated a synergistic effect in downregulating the expression of HIF-1α and β-catenin, which were further diminished upon the addition of shikonin, a specific inhibitor of PKM2. LY294002 treatment further reduced the expression of GLUT1, PKM2, and LDHA proteins induced by combined L-arginine and 5-FU treatment compared to the combined group. However, the reduction in p-PI3K, p-AKT, and GLUT1 expression caused by L-arginine and 5-FU combination was also reversed in HepG2 and SMMC7721 cells with iNOS knockdown, respectively. Additionally, the combination of L-arginine and 5-FU led to a greater reduction in the enzymatic activity of ALT, AST, G6PDH and LDH, as well as a significant reduction in hepatic index, AFP, AFP-L3, ATP and LD levels in a rat model of HCC. Moreover, the simultaneous administration of L-arginine and 5-FU significantly improved the gross morphology of the liver, reduced nuclear atypia, inhibited the proliferation of cancer cells, and decreased the expression levels of p-PI3K, p-AKT, GLUT1, PKM2, and LDHA, while iNOS expression was increased in the combination group. Taking together, L-arginine and 5-FU combination resulted in the inhibition of enzymes in aerobic glycolysis via the iNOS/NO/AKT pathway, which led to the suppression of glucose metabolism and downregulation of nuclear transcription factors, thereby impeding the proliferation of hepatocellular carcinoma cells.

The release rate and time are very important for the drug carriers, silica aerogel filled hydroxypropyl cellulose/chitosan (SA/HPC/CS) composites were fabricated for the release of 5-fluorouracil (5-Fu), and the release rate and time were regulated with the content of SA, pH value and external coating material. Firstly, the 5-Fu loaded SA/HPC/CS composites and Eudragit L100 coated composites were prepared with cross-linking followed by freeze-drying, and characterized by SEM, FTIR, XRD, DSC, and TG. Then, the effect of SA content on the encapsulation efficiency of SA/HPC/CS@5-Fu was investigated, and 5-Fu release behavior under different pH values from these aerogel composites was evaluated with four kinetic models. In addition, to further solve the abrupt effect of the obtained composites, Eudragit L100 coated SA/HPC/CS@5-Fu was fabricated, the sustained release behavior revealed that the coating technique can effectively improve the release behavior and extend release time.