جستجوی مقالات مرتبط با کلیدواژه « 5-fluorouracil » در نشریات گروه « پزشکی »

Colorectal cancer (CRC) remains a major health concern worldwide due to its high incidence, mortality rate, and resistance to conventional treatments. The discovery of new targets for cancer therapy is essential to improve the survival of CRC patients. Here, this study aims to present a finding that identifies the STAT6 oncogene as a potent therapeutic target for CRC. HT-29 CRC cells were transfected with STAT6 siRNA and treated with 5-fluorouracil (5-FU) alone and combined. Then, to evaluate cellular proliferation and apoptosis percentage, MTT assay and annexin V/PI staining were carried out, respectively. Moreover, the migration ability of HT-29 cells was followed using a wound-healing assay, and a colony formation assay was performed to explore cell stemness features. Gene expression was quantified via qRT-PCR. Afterward, functional enrichment analysis was used to learn in-depth about the STAT6 co-expressed genes and the pathways to which they belong. Our study shows that silencing STAT6 with small interfering RNA (siRNA) enhances the chemosensitivity of CRC cells to 5-FU, a commonly used chemotherapy drug, by inducing apoptosis, reducing proliferation, and inhibiting metastasis. These results suggest that combining 5-FU with STAT6-siRNA could provide a promising strategy for CRC treatment. Our study sheds light on the potential of STAT6 as a druggable target for CRC cancers, the findings offer hope for more effective treatments for CRC patients, especially those with advanced stages that are resistant to conventional therapies.

CD44 plays a pivotal role through tumorigenesis by regulating cancer cell metastasis, stemness, and chemosensitivity and is considered a promising therapeutic target for human cancers, including colorectal cancer (CRC). Therefore, the present research aimed to examine the simultaneous therapeutic effect of CD44 silencing and 5-fluorouracil (5-FU) on in vitro tumorigenesis of CRC cells.

CD44 expression was initially evaluated in TCGA datasets and CRC tissues. Furthermore, functional analysis was performed on HT-29 CRC cells overexpressing CD44. The cells were transfected with CD44 siRNA and then treated with 5-FU. Consequently, to explore the combination therapy effect on cell viability, migration, apoptosis, and chromatin fragmentation, we performed MTT assay, scratch assay, Annexin V/PI staining and DAPI staining assays, respectively. The spheroid and colony formation assays were further employed to investigate stemness features. The gene expression at protein and mRNA levels were explored using western blotting and qPCR.

Our findings illustrated that CD44 was significantly overexpressed in CRC tissues compared to normal samples. The suppression of CD44 considerably promoted the chemosensitivity of HT-29 cells to 5-FU by apoptosis induction. Also, the combination therapy led to overexpression of apoptotic genes, including P53, caspase-3, and caspase-9, as well as downregulation of AKT1 expression. Furthermore, CD44 suppression, separately or combined with 5-FU, hindered stemness properties in HT-29 cells via downregulation of Sox2 and Nanog expression. Besides, the combination therapy remarkably downregulated MMPs and suppressed CRC cell migration.

Considering its involvement in chemosensitivity to 5-FU, CD44 could be suggested as a potential target for improving the efficiency of CRC chemotherapy.

Benign fibroproliferative scars that are larger than the initial lesion are called keloids. Keloids treatment in clinical practice is still difficult. Although there are various therapy choices, none is embraced by everyone or is relapse-free. Various treatment modalities such as intralesional corticosteroid injection with 5-fluorouracil (5-FU), fractional Er:YAG laser, pulsed dye laser (PDL), and others can be used either as monotherapies or combined therapies. Therefore, efforts should be made to select the treatment that will provide the best results.

A 6-year-old boy with keloids on the lower lips extending to the chin was successfully treated with a 2940-nm fractional Er:YAG laser alternated with a 595-nm long-PDL followed by the combined intralesional injection of corticosteroid and 5-FU. The patient was followed up for 1 year with no lesion recurrence.

Our case supports a combined therapy to successfully treat a patient with a keloid on the chin. Therapy using a combination of these four modalities seems safe and effective and may have a synergistic effect with minimal downtime.

Cancer treatment using drugs metabolized by the enzymes dihydropyrimidine dehydrogenase (DPYD) and UDP-glucuronosyltransferase 1A1 (UGT1A1) results in adverse effects for some patients. This is frequently reported in cancer patients undergoing therapy with 5-fluorouracil, capecitabine, and irinotecan who have polymorphisms in the genes coding for DPYD and UGT1A1. The present study assessed the DPYD*2A and UGT1A1*28 polymorphisms in cancer patients before starting chemotherapy to identify the individuals at risk of developing an adverse drug reaction.

Genomic DNA was isolated from patients and subjected to PCR amplification using specific primers to study DPYD*2A and UGT1A1*28 polymorphisms. The PCR products were assessed by Sanger sequencing for establishing the genotype.

Of 75 cancer patients requiring treatment with drugs metabolized by DPYD and UGT1A1, 2 (2.66%) and 12 (29.27%) were likely to have adverse reactions based on DPYD*2A and UGT1A1*28 genotyping, respectively.

Our findings indicate that carrying out genotyping for these two polymorphisms will help a large number of patients requiring treatment with 5-fluorouracil, irinotecan, and capecitabine.

Aberrant activation of the WNT/β-catenin signaling pathway is involved in various types of cancers, particularly colorectal cancer (CRC), which is a prevalent malignancy. Targeting the Wnt signaling pathway has gained a reputation as an attractive therapeutic strategy, mainly because of its potential for regulating cell proliferation, migration, differentiation, angiogenesis, and apoptosis.

The aim of the current research was to investigate the effects of 5-Fluorouracil (5-FU) and bovine alpha-lactalbumin made lethal to tumor cells (BAMLET), a complex of oleic acid with bovine α-lactalbumin protein, on colon cancer cells focusing on the Wnt signaling pathway.

For this purpose, HT-29 and HCT116 cells were treated with 5-FU and BAMLET, and the expression levels of Wnt signalingrelated proteins (β-catenin andE-cadherin) andVEGF as angiogenesis regulators were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR) and Western Blot analysis.

Bovine alpha-lactalbumin made lethal to tumor cells (BAMLET) treatment down-regulated the expression of β-catenin and up-regulated the expression of E-cadherin significantly compared to the 5-FU (P < 0.0001). The reduced mRNA levels of VEGF in treated cells revealed the effectiveness of 5-FU and BAMLET on angiogenesis.

Bovine alpha-lactalbumin made lethal to tumor cells (BAMLET) can be considered for targeting the Wnt signaling pathway and angiogenesis. It is amenable to further investigation in the development of CRC treatment.

Several pharmaceutical formulations were investigated to improve the solubility of 5-fluorouracil to enhance bioavailability and therapeutic efficacy. This study aimed to examine the potential use of cyclodextrin-based nanosponges for the incorporation of 5-fluorouracil and to investigate the use of different crosslinking agents on the properties of the resulting drug carrier. 5-Fluorouracil complexation with β-cyclodextrin was also studied to explain the unexpected results of weak 5-fluorouracil incorporation in nanosponge.

Nanosponges were synthesized by crosslinking β-cyclodextrin with two different crosslinkers; diphenyl carbonate and ethylenediaminetetraacetic dianhydride. The incorporation of 5- fluorouracil into β-cyclodextrin and the prepared nanosponges were assessed by NMR, FTIR, PXRD, DSC, and TGA. In addition, an in vitro release study was carried out to evaluate the potential use of β-cyclodextrinbased nanosponges as pharmaceutical formulations for 5-fluorouracil. Findings /

Physicochemical characterization of the dried formulations indicated the complexation of 5-fluorouracil with the β-cyclodextrin polymer. Despite that, no clear manifestation of 5-fluorouracil encapsulation in the prepared β-cyclodextrin-based nanosponge was detected. Furthermore, no significant differences were observed in the release profiles of 5-fluorouracil, β-cyclodextrin complex, and βcyclodextrin-based nanosponge, suggesting weak complexation and instability in aqueous solutions. EDTAcrosslinked β-cyclodextrin-based nanosponge showed a slight improvement in 5-fluorouracil solubility with a faster initial rate of 5-fluorouracil release.

This study suggested weak complexation between 5-fluorouracil and the βcyclodextrin polymer or nanosponges. Crosslinking of β-cyclodextrin with EDTA dianhydride crosslinker showed an enhancement in 5-fluorouracil saturation solubility combined with a faster initial rate of drug release.

Breast cancer (BC) cells’ ability to metastasize to other tissues increases mortality. The Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) facilitate cancer cell migration. 5-fluorouracil is a frequently applied chemotherapeutic agent in cancer treatment with destructive side effects on normal tissues. Hence, researchers have focused on finding a way to reduce the dose of chemotherapeutic drugs. Quercetin, a natural polyphenolic compound, has inhibitory effects on proliferation and migration of tumor cells. This study evaluated the effect of the combination of Quercetin and 5-fluorouracil  on migration of the MDA-MB-231 breast cancer cell line. The effect of Quercetin, 5-fluorouracil , and their combination on MDA-MB-231 breast cancer cell proliferation was investigated through MTT assay. Inhibition of tumor cell migration was examined by wound healing assay. Finally, the effect of treatments on gene expression of MMP-2 and MMP-9 was evaluated by quantitative real-time PCR. The IC50 values for Quercetin and 5-fluorouracil  after 48 hr treatment were 295 μM and 525 μM, respectively. The combination index (CI) for Quercetin and 5-fluorouracil  was <1, indicating synergy between them. The combination of Quercetin plus 5-fluorouracil  resulted in a significant reduction in migration rate and MMP-2 and MMP-9 gene expressions of MDA-MB-231 cancer cells compared with the individual application of 5-FU. Quercetin enhances the suppressory effect of 5-fluorouracil  on migration of BC cells. The combination of Quercetin and 5-fluorouracil  can be an attractive field for future studies.

The most important side effect after non-surgery cancer treatment (NSCT) is oral mucositis (OM) which degrades the quality of life. Using photobiomodulation (PBM), formerly known as low-level laser therapy (LLLT), in the prevention of NSCT-induced OM was widely studied. Hence, this review evaluates the efficacy of optical treatment parameters behind the working process of PBM in preventing NSCT-induced OM in preclinical studies.

Using the PubMed, Scopus and Embase databases, the present study systematically reviewed existing preclinical studies for optical treatment parameters of PBM in preventing NSCT-induced OM in experimental models without restriction on the year of publication.

In total, 51 articles were recognized during the search of the literature, and only 16 research papers were included in this review, taking into consideration the inclusion as well as exclusion benchmarks. The reviewed studies showed that a consensus has yet to be reached on the optimal PBM treatment parameters in preventing NSCT-induced OM. However, a wavelength of 660 nm, a power density of 40 mW as well as fluence which ranged between 2 and 6 J/cm2 were mostly utilized in the included studies. Furthermore, the severity of NSCT-induced OM was reduced following PBM application with no reported severe side effects.

The efficacy of PBM with the associated optical parameters is a promising strategy in preventing NSCT-induced OM. However, the optimal parameters of PBM need to be investigated.

The hepatotoxic effect of 5-fluorouracil (5-FU) can deprive cancer patients of its maximum therapeutic benefits. Selenium (Se) is a trace element with potential benefits in some animal models of diseases.

This study assessed the ability of Se to nullify the hepatotoxic effect of 5-FU in albino rats. 

In this study, 40 adult male albino rats were grouped into A to D (each 5 rats). Rats in group A (control) were treated intraperitoneally (IP) with normal saline (0.2 mL) daily for 5 days. Rats in groups B1 to B3 were treated IP with Se (0.125, 0.25, and 0.50 mg/kg) daily for 5 days, respectively. Rats in group C were treated IP with 5-FU (20 mg/kg) daily for 5 days. Rats in groups D1to D3 were treated IP with Se with 0.125, 0.25, and 0.50 mg/kg before treatment with 5-FU (20 mg/kg) daily for 5 days, respectively. After treatment, the rats were euthanized, and their blood samples were collected and evaluated for serum liver function. Liver samples were evaluated for biochemical and histological parameters.

Liver and serum aminotransferases, gamma-glutamyl transferase, lactate dehydrogenase, alkaline phosphatase, total bilirubin, and conjugated bilirubin levels were significantly (P<0.001) high in 5-FU-treated rats in comparison to the control group. Liver glutathione peroxidase, superoxide dismutase (SOD), catalase, and glutathione levels were significantly (P<0.001) low whereas the malondialdehyde level was significantly (P<0.001) high in 5-FU-treated rats compared with the control group. Moreover, hepatocyte necrosis was observed in 5-FU-treated rats. 

Nonetheless, 5-FU-induced hepatotoxicity was significantly nullified in rats supplemented with Se (0.125 mg/kg, P<0.05; 0.25 mg/kg, P<0.01, and 0.5 mg/kg, P<0.001) in a dose-dependent fashion in comparison to 5-FU-treated rats. Thus, Se may have a clinical benefit in 5-FU-induced hepatotoxicity

Several studies have been conducted to find suitable combinations of drugs to increase the efficacy of chemotherapy and reduce the resistance of tumor cells to treatment. Lipopolysaccharide (LPS), as a ligand for Toll-like receptor 4 (TLR-4), can modify immune responses in different cancers. Although multiple studies have been performed in this area, the effect of LPS on tumor cells remains controversial. In the present study, the cytotoxic effects of 5-fluorouracil (5-FU), with or without LPS, were evaluated in human breast cancer cell line (MCF-7) on apoptosis and gene expression in downstream signaling pathways. MCF-7 was obtained from the Pasteur Institute of Iran. The effects of LPS and 5-FU on cytotoxicity, apoptosis, and gene expression in NF-κB, ERK, and AKT signaling pathways were evaluated by MTT assay, Annexin V/propidium iodide (PI) apoptosis assay, and qRT-PCR, respectively. Our findings showed that LPS alone did not significantly affect cytotoxicity or apoptosis, compared to the control cells (untreated cells), while combined with 5-FU, it caused a significant increase in the apoptosis of cancer cells and decreased cell viability. It was also concluded that LPS in combination with 5-FU increased TLR-4 expression and down-regulated gene expression in NF-κB, ERK, and AKT pathways (p=0.001). Although the role of LPS in tumor inhibition or progression remains controversial, our findings suggest that LPS can be considered a novel complementary approach intranslational oncology research of breast cancer therapy.

Oral mucositis (OM) has been considered one of the most feared collateral effects of oncological treatments. Some therapies have been used, such as light-emitting diode (LED), with promising results, but with no sufficient evidence in the literature.

Our study aimed to evaluate, by clinical and histological analysis, the effect of LED on the treatment of chemotherapy-induced OM (CIOM) in an animal model.

Twenty male hamsters were equally distributed to two groups: control (C), which received anesthesia and CIOM induction; and LED (L), which received anesthesia, CIOM induction, and LED treatment (635 nm, 120 mW, 0.48 J). The clinical analysis was performed through two specific scales for OM analysis on days 5, 7 and 10 of the experiment. In addition, the injured area of all hamsters check pouch mucosa was removed and processed for histological analysis on the last experimental day.

After statistical analysis, group L showed less severity of OM when compared with the C group (P < 0.05); beyond that, both healed completely on day 10.

Our results suggested that the phototherapy with LED had a positive effect on accelerating repair, reducing the severity of CIOM.

The fluoropyrimidine drug 5-Fluorouracil (5-FU) and the prodrug capecitabine have been extensively used for treatment of many types of cancer including colorectal, gastric, head and neck. Approximately, 10 to 25% of patients suffer from severe fluoropyrimidine-induced toxicity. This may lead to dose reduction and treatment discontinuation. Pharmacogenetics research could be useful for the identification of predictive markers in chemotherapy treatment. The aim of the study was to investigate the role of five genetic polymorphisms within two genes (DPYD, TYMS) in toxicity and efficacy of fluoropyrimidine-based chemotherapy.

Total genomic DNA was extracted from 83 cancer patients treated with fluoropyrimidine-based chemotherapy. In this study, three polymorphisms were genotyped in dihydropyrimidine dehydrogenase gene c.1905+1 G>A (DPYD*2A; rs3918290), c.1679 T>G (I560S; DPYD*13; rs55886062), and c.2846A>T (D949V; rs67376798) and two polymorphisms, besides the Variable Number of Tandem Repeat (VNTR) polymorphism and 6-bp insertion/deletion polymorphism in thymidylate synthase gene. The analysis of polymorphisms for rs3918290, rs55886062, rs67376798 and 6-bp insertion/ deletion in TYMS was done by Polymerase Chain Reaction-restriction Fragment Length Polymorphism (PCRRFLP) TYMS VNTR analysis. 5-FU-related toxicities such as anemia, febrile neutropenia, neurotoxicity, vomiting, nausea, and mucositis were evaluated according to NCI-CTC criteria version 4.0. T-test and chi-square were used and p-values less than 0.05 were considered statistically significant.

DPYD gene polymorphisms were not observed in this study. The frequency of the TYMS +6 bp allele was 40.35% and the -6 bp allele was 59.65% in this study. The frequency of VNTR 2R allele was 48.75% and 3R allele was 51.15%. Toxicity grade II diarrhea, mucositis, nausea, vomiting, and neurotoxicity was 2.2, 24.1, 15.7, 6, and 51.8%, respectively. Thymidylate synthase ins/del polymorphisms were associated with increased grade III neurotoxicity (p=0.02). Furthermore, anemia grade III was significantly associated with 2R/2R genotype (0.009).

Thymidylate synthase gene polymorphisms may play a key role in fluoropyrimidne -based chemotherapy. Although rare DPYD polymorphisms were not observed in our study, according to large population studies, DPYD gene polymorphisms could be used as a predictive biomarker for patient treatments.

Colorectal cancer (CRC) is a prevalent cancer worldwide. The present study aimed to synthesize and investigate the potential of wheat germ agglutinin (WGA) conjugated with polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) incorporating 5-fluorouracil (5-FU).

The NPs were investigated in terms of various characteristics, such as the particle size, surface charge, surface morphology, entrapment efficiency rate, and in-vitro drug release profile in simulated gastric and intestinal fluids. The optimized NPs were conjugated with WGA and characterized for the WGA conjugation efficiency, mucoadhesion, and cytotoxicity studies.

The zeta potential of the WGA-conjugated NPs decreased (-17.9±1.4 mV) possibly due to the conjugation of the NPs with WGA, which reduced the zeta potential. The WGA-conjugated NPs exhibited sustained drug release effects (p<0.05) compared to the marketed formulation containing 5-FU after 24 hours. In addition, the optimized NPs followed the Higuchi kinetics, showing diffusion-controlled drug release mechanisms. Finally, the WGA-conjugated PLGA NPs could significantly inhibit the growth of colon cancer cells (HT-29 and COLO-205) compared to the non-conjugated NPs and pure drug solution (P<0.05).

According to the results, the WGA-conjugated NPs could be potential carrier systems compared to the non-conjugated NPs for the effective management of CRC.

The aim of this study is to prepare 5-fluorouracil (5-FU) loaded silk fibroin nanoparticles(SFNPs) and to achieve a controlled release delivery system with the high loading capacity.

SFNPs with 1:1, 1:3, and 1:10 ratios of 5-FU to silk fibroin were prepared. SFNPswere characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD)analysis, Scanning electron microscope (SEM), and Transmission electron microscope (TEM).Loading efficiency, in vitro release, and cell viability were studied for optimal SFNPs.

The ratio of 1:1 was optimal formulation with the size and polydispersity index (PDI)of 221.03 nm and 0.093 before freeze drying, and 286.7 nm and 0.154 after freeze dryingby lactose, respectively. The loading efficiency and loading content of this ratio were 52.32%and 34.35%, respectively. FT-IR and XRD analysis indicated the conformational change (fromrandom coil to β-sheet) in the structure of nanoparticles by increasing amount of the drug, whichcaused the smaller size, the higher loading efficiency, and the slower release pattern. The drugloadednanoparticles reached to the half maximal inhibitory concentration (IC50) that werecomparable with free drug on MCF7 (human breast cancer) cell line.

This study was planned to achieve a promising controlled release drug deliverysystem for carrying 5-FU, as a potent anticancer drug. SFNPs were found proper candidates fordelivery of a hydrophilic drug such as 5-FU.

Keratocystic odontogenic tumors (KOT) have a high rate of recurrence, which is higher in patients diagnosed with Gorlin-Goltz syndrome (GGS). Adjunctive therapies, such as fixative chemical solutions, decrease the rate of recurrence after enucleation and peripheral ostectomy but have high morbidity rates. Topical 5-Fluorouracil (5-FU) has been suggested as a new therapy that provides a directed molecular approach to treatment.

This is a case report of GGS treated using topical 5-FU as an adjunctive material after enucleation and peripheral ostectomy. New bone formation sites were identified in the radiographic follow-up. The patient was followed up for 10 months regularly without any evidence of recurrence.

5-FlU is an effective and novel targeted treatment for KOTs. Topical application of 5-FU, following enucleation and peripheral ostectomy, effectively treats syndromic KOTs, resulting in normal bony healing with no adverse local or systemic effects.

One of the most common malignancies in women is breast cancer. B-escin has pharmacological anticancer effects. 5-fluorouracil (5-FU) has antimetabolite and antiproliferative properties. The purpose of this study was to investigate the combined effects of 5-FU and B-escin on apoptosis, colony formation, Bcl-2 signaling protein, and p53 gene expression in MCF7 breast cancer cell line. The cytotoxic effects, the number of colonies, apoptosis, p53 gene expression, and Bcl-2 signaling protein of the combined 5-FU and B-escin on MCF7 cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, clonogenic assay, flow cytometry, real-time quantitative polymerase chain reaction, and western blotting methods, respectively. Half-maximal inhibitory concentration values of B-escin and 5-FU were 80 Micro g/ml and 2 Micro M, respectively. The combination of 5-FU and B-escin on MCF7 cell viability showed a combination index equal to 0.5. The expression of p53 and apoptosis increased in the combination of 5-FU and B-escin on MCF7 cells compared to that of control group (P < 0.05). In addition, the number of colonies and Bcl-2 signaling protein in combination of 5-FU and B-escin decreased with respect to untreated control cells or single treatment of 5-FU and B-escin. The combination of 5-FU and B-escin not only has synergistic effects by increasing cell apoptosis and p53 gene expression but also decreases Bcl-2 signaling protein in MCF7 cell lines.