Background: Fluoropyrimidines are widely used in the treatment of various solid tumors. One-third of cancer patients develop severe treatment-related toxicity. A part of fluoropyrimidine-related toxicity arises due to impaired activity of dihydropyrimidine dehydrogenase (DPD) caused by genetic variants in the DPYD gene. Objective: This study aims to determine the frequency of DPYD mutations among patients with adverse effects of 5-fluorouracil therapy. Materials and Methods: This cross-sectional study recruited 46 patients with 5-FU adverse effects. All demographic, clinical, and laboratory findings were recorded. Molecular testing was conducted to detect the DPYD mutation using the PGX-5FU StripAssay® kit, which identifies the IVS14 + 1G>A DPYD variant (DPYD*2A), the most common DPYD mutation. Results: The majority of the 46 recruited Iraqi Arab patients were females (71.74%), and the most common age groups were 41–50 and 51–60 years (26.08%) each. The most common cancer was breast cancer (45.65%). Poorly differentiated tumors were the most common grade (60.86%), and stage 3 was the most common tumor stage (47.82%). 5-FU was used as a single agent in 19.57%. The most common adverse effects reported were alopecia, vomiting, anemia, fatigue, diarrhea, and neutropenia. Molecular testing revealed that all patients had the wild-type DPYD IVS14 + 1G>A genotype. Conclusions: This study supports the evidence that routine testing for DPYP mutation in patients receiving 5-FU is not cost-effective and that selected patients can be tested if they show toxic reactions suggestive of DPD deficiency. Testing for four common variants of the DPYD gene can achieve better results.
5-fluorouracil (5-FU) is a is Pyrimidine analogue widely used in the treatment of various malignancies It belongs to the antimetabolites family that acts during the S-phase of the cell cycle thus it prevents DNA synthesis.N-acetylcysteine is nutritional complement acts as antioxidant.The purpose of the current study is to investigate whether there is a protective role of N-acetylcystein against intestinal toxicity induced by 5-fluorouracil in albino rats.18 healthy adult rats were distributed into 3 groups of 6 rats for each. Group A as a control group.Group B injected with 5-FU (20 mgs dissolved in 2ml normal saline per kilogram body weight intraperitoneally for 7 successive days while Group C received N-acetylcy
... Show MoreThe intestinal mucositis define as inflammation and ulceration in the gastrointestinal tract wall and in some case in the oral cavity these cause by treatment with antineoplastic drug like 5-fluorouracil and Irinotecan and other types of chemotherapeutics drugs , 5-Fluorouracil-induced intestinal mucositis (IM) is consider as one of the more common tumor issue .it cause series of undesirables symptoms like severe diarrhea ,abdominal pain , stomach uncomfortable and other. The aim of this current study to see how ellagic acid act to Attenuates 5-FU-Induced Intestinal Mucositis and Diarrhea in Mice . we induced the intestinal mucositis by injected the mice intraperitoneally in 5-fluorouracil about 50mg per kg daily for
... Show MoreCardiac toxicity can occur during the therapy with several cytotoxic drugs, including 5- Fluorouracil (5- FU). It is an antimetabolite that acts during the S phase of the cell cycle and is activated by thymidine phosphorylase into fluorodeoxyuridylate (5 fluoro 2'deoxyuridine 5'monophosphate, 5-FdUMP) that inhibits thymidylate synthase, thus preventing DNA synthesis that leads to imbalanced cell growth and ultimately cell death. It is still a widely used anticancer drug, since 1957. The present study aimed to evaluate the possible cardio-protective effects of ethanolic artichoke extract (Cynara scolymus L.) against 5-fluorouracil (5-FU) induced cardio-toxicity in rats by evaluating serum levels of Alanine aminotransferase, aspartate amin
... Show MoreBackground Radiotherapy is one of the main modalities in the management of cancer along with chemotherapy and surgery. Despite its great benefit it has many side effects on many systems and organs including the skin. Objective To record the frequency, grades and types of acute cutaneous side effect in patients with pelvic tumors treated with radiotherapy, in order to report the risk factors and to find appropriate strategies for prevention and management. Patient and methods. Methods A prospective observational study was carried out in Baghdad Radiation and Nuclear Medicine Centre between August 2020 and August 2021.A total 70 patients were enrolled in this study.All patients had full history and full baseline skin exam and were ass
... Show More5-florouracil is a widely used anticancer/anti-metabolite drug used to treat solid tumor like colon cancer, head and neck, rectum, stomach, pancreas and breast cancer; but, it can cause hepatotoxicity by induction of apoptosis through activation of caspases enzymes and oxidative stress. Nobiletin is a citrus fruit-derived flavonoid that possess significant biological activity, including anticancer, and anti-inflammatory. This study was design to investigate the effects of nobiletin against 5-florouracil-indcued hepatotoxicity in male rats through the measurement of selected -inflammatory, -apoptosis, and -oxidative stress markers. By use male Albino rats weighing 150-250gm around 28 animals; giving them tap water ad libitum and fed commerci
... Show MoreIn the present study, five derivatives have been designed to be synthesized as possible mutual prodrugs for 5-Fluorouracil (5-FU) and non steroidal anti-inflammatory drugs (NSAIDs) to selectively deliver the drugs into the cancer cells. The synthesis of the target compounds were accomplished following multistep reaction procedures, the chemical reaction followed up and the purity of the products were checked by TLC. The structure of the final compounds and their intermediates were confirmed by their melting points, infrared spectroscopy and elemental microanalysis, the hydrolysis of compound III was studied using HPLC technique. According to the results mentioned above, compounds (I−V) can be good candidates as possible mutual prod
... Show More5-Fluorouracil is one of the commonly used chemotherapy drugs in anticancer therapy; unfortunately treatment with 5-FU by solely has many drawbacks low lipophilicity, low permeability, low molecular weight, and its relatively poor plasma protein binding; also a brief half-life therefore frequent administration is required to maintain the optimal therapeutic plasma level which in addition to its poor selectivity, drug resistance and limited penetration to cancer cells; leads to increased incidence of side-effects to healthy cells/tissues and low response rates. In order to minimize these drawbacks; 5-FU was chemically conjugated with pyrrolidine dithiocarbamate (PDTC) in a mutual prodrug moiety (S-(9H-purin-6-yl) 3-(
... Show MoreObjective: This study was designed to investigate some possible therapeutic mechanisms of pentoxifylline and sildenafil in the treatment of colorectal carcinoma induced by 1, 2 dimethylhydrazines in rats. Methods: Rats were allocated into seven groups, negative control, colon cancer induced by 1,2,dimethylhydrazine, 5-fluorouracil (5-FU) (50 mg/kg)-treated, pentoxifylline (PTX) (50 mg/kg)-treated, sildenafil (0.7 mg/kg)-treated groups; the two other groups set as colon cancer induced group treated with PTX (50 mg/kg) plus 5-FU(50 mg/kg) and sildenafil (0.7 mg/kg) plus 5-FU (50 mg/kg), respectively. Results: Biochemical results revealed significant elevation of serum carcinoembryonic antigen (CEA) levels, carbohydrate19-9 antigen (CA19-9) as
... Show MoreBackground. Gene polymorphisms affect etanercept’s pharmacokinetics, pharmacodynamics, and side effects. This effect is evidenced by the extensive genetic variation in the drug’s targets. Objectives. This study aims to find the association between different genotypes of the promoter region of the TNF-α gene at -308G/A(rs1800629), -857C/T(rs1799724), -863 C/A(rs1800630), -1031 T/C (rs1799964), -806 C/T (rs4248158) and -376 G/A (rs1800750) and the side effects of ETN that occurred to Iraqi RA patients. Method. The trial included patients with rheumatoid arthritis who had been using ETN for at least six months. The participants were from the Baghdad Teaching Hospital Rheumatology Unit. The PCR was sequenced to determine the polymo
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