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This study was designed to evaluate the effect of Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms on MTX toxicity in pediatric Egyptian ALL patients. Ninety-Four of Pediatric ALL patients aged 3-13 years (7.6 ± 3.6) on oral maintenance dose of 50 mg/m2 weekly of MTX. MTHFR c.677C>T (rs1801133) and c.1298A>C (rs1801131) genotyping were performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The allele frequencies of c.677C>T were 42.6%, 46.8%, and 10.6% for CC, CT, and TT respectively, while c.1298A>C alleles frequencies were 62.7%, 24.5%, and 12.8% for AA, AC, and CC respectively. None of the investigated polymorphism (C677T or A1298C alleles) was associated with either overall or site specific MTX toxicity regarding anemia (p = 0.99) (p = 0.4), platelets (p = 0.4) (p = 0.4), hepatotoxicity (p = 0.4) (p = 0.7), respectively. The results indicated that between c.677C>T genotypes, CC/CT and TT were associated with hematopoietic toxicities 60.7% and 60% (p = 0.2); platelet toxicities 76.2% and 80% (p = 1) and, hepatotoxicities 40.5% and 60% (p = 0.3), respectively. In the c.1298A>C genotypes, CC/AC and AA presented hematopoietic toxicities 68.6% and 55.9% (p = 0.2), platelet toxicities 82.9% 72.9% (p = 0.3) and, hepatotoxicity 37.1% and 45.8% (p = 0.5), respectively. No significant associations were detected between MTHFR c.677C>T or c.1298A>C polymorphisms and either overall or site specific MTX toxicity.Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a ubiquitous multifunctional protein required in the DNA base excision repair pathway and a noteworthy reducing-oxidizing factor that regulates the activity of various transcription factors. Cyclin-dependent kinases (CDKs) assume a key role in directing the progression of the cell- cycle. The present study evaluated the synergistic efficacy of using licochalcone B (LCB) and fullerene C60 (FnC60) nanoparticles against diethylnitrosamine (DEN)-induced hepatocarcinoma in rats and relevant signaling pathways, with APE1/Ref-1 and CDK-4, as novel anti-cancer- targeting. LCB alone and in combination with FnC60 significantly decreased DNA fragmentation, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine levels), APE1/Ref-1, CDK-4, retinoblastoma, B- cell lymphoma-2 (Bcl-2), B-cell lymphoma-xL (Bcl-xL), and β-arrestin-2 mRNA expression, and APE1/Ref-1 and CDK-4 protein expression. In contrast, these treatments significantly increased the expression of protein 53 (p53), Bcl-2-associated X protein (Bax), and caspase-3. These data suggest that LCB either alone or in combination with FnC60 elicited significant protective effects against DEN-induced hepatocarcinogenesis, which may have occurred because of the regulation of enzymes involved in DNA repair and cell-cycle control at S phase progression as well as the induction of apoptosis at the gene and protein expression levels. Furthermore, FnC60 potentiated the effect of LCB at the molecular level, possibly through targeting of cancerous cells.This study aims to evaluate the clinical outcomes and the toxicities associated with intensity modulated radiotherapy (IMRT) administered in combination with capecitabine for gastric cancer. Acetylcysteine This study was conducted between July 2009 and October 2011, and included 31 patients (23 female and eight male patients; mean age 57 years old) with pathologically confirmed gastric cancer (pathological staging T3 or T4 or positive lymph node). All patients underwent D2 surgery and adjuvant chemoradiotherapy, followed by combined treatment with IMRT and capecitabine. All patients received follow-up examinations every 3-6 months by physical examination, magnetic resonance imaging (MRI), and assays for tumor markers. The Kaplan-Meier method was used to calculate the rates for locoregional control (LRC) and disease-free survival (DFS). Only two patients could not complete the planned treatment regimen. Patients treated with IMRT and capecitabine tolerated their treatment well, and displayed few significant side effects. The mean follow-up, disease-free survival (DFS) and survival times were 33.0, 27.5, and 32.9 months, respectively.This study confirmed that the combined administration of IMRT and capecitabine can be used as an adjuvant therapy for gastric cancer patients, with few toxic side effects.Quince (Cydonia oblonga Mill.) is one of the medicinal plant with a broad range of pharmacological activities such as hepatoprotective effect. The present study was conducted to evaluate the effect of aqueous extract of Cydonia oblonga Mill. fruit (ACOF) against carbon tetrachloride (CCl4)-induced liver damage in rats. Hepatotoxicity was induced by CCl4 and all tested group animals were treated with the plant extract at a dose of 75, 150, and 300 mg/kg orally for 5 days. Blood was collected for the assessment of serum marker enzymes (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)). Adenosine triphosphate (ATP) of liver mitochondria was also measured using a validated high performance liquid chromatography (HPLC) method. The antioxidant capacity of the extract resulted in the reduction of MDA and the restoration of GSH in the liver (P less then 0.05). Free radical scavenging activity of the extract was evaluated by DPPH method and the IC50 value was found to be 568 μg/mL. Our results indicated that bioenergetic depletion occurred in the intoxicated rats as a consequence of mitochondrial dysfunction and ATP production collapse. ACOF markedly restored ATP contents that is a key step in liver regeneration. It can be concluded that the role of ACOF to improve liver function on CCl4-hepatoxicity could be attributed, at least partially, to its action at mitochondira by preventing the loss of ATP content.
This study aimed to characterize and evaluate leishmanicidal and trypanocidal action as well as cytotoxicity on macrophages and antioxidant ability of extracts, obtained by supercritical CO
and ultrasound-assisted extractions of Uvaia (
) leaves.
Leaves from
were submitted to supercritical CO
(E1) and ultrasound-assisted (E2) extractions. The characterization of extracts was done using GC-MS and HPLC.
(promastigotes) and
(epimastigotes and trypomastigotes) were treated with crescent concentrations of E1 and E2. After this, parasites were counted and the percentage of inhibition and IC
/LC
was calculated. Murine macrophages were treated with both extracts for 48 h and after that, the cellular viability was determined and CC
was calculated. DPPH method was used to determine the antioxidant capacity of both extracts.
The results of identification showed a great amount of α and β-amyrin in E1 and E2. Both extracts showed growth inhibition of
with an IC
of 5.98 and 9.38 μg/mL to E1 and E2, showing a selectivity index > 30.
My Website: https://www.selleckchem.com/products/acetylcysteine.html
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