• Biomolecules & Therapeutics
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• 제32권5호
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• pp.647-657
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• 2024

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat. This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression. Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.775-780
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• 2012

8-isoprostane (8-$isoPGF_{2{\alpha}}$) is a reliable marker and considered a gold standard for lipid peroxidation. There are very few reports of 8-isoprostane levels in cancer patients, and in patients undergoing chemotherapy. Oxidative stress is however expected and has been observed in patients with cancer. This study measured 8-isoprostane levels in urine by ELISA of 25 patients undergoing chemotherapy for advanced non-small cell lung cancer, at cycles 1, 2, and 3 of treatment. It considers the creatinine clearance of the patients, and correction of 8-isoprostane levels by creatinine clearance, and overnight urine volume methods. The average 8-isoprostane levels in urine increased more than 6 to 12 fold on chemotherapy treatment, from $532{\pm}587$ pg/mL at cycle $1,6181{\pm}4334$ at cycle 2, and $5511{\pm}2055$ at cycle 3. Similar results were obtained if 8-isoprostane levels were corrected for overnight urine volume, giving averages of $285{\pm}244{\mu}g$ at cycle $1,4122{\pm}3349$ at cycle 2, and $3266{\pm}1200$ at cycle 3. No significant difference was seen in average total overnight urine volume or number of urinations between chemotherapy cycles except for a large variation in urine volume between cycle 2 and 3. Creatinine levels were significantly different only between cycles 1 and 2 (p=0.016). In conclusion, cisplatin therapy has been shown to induce high levels of lipid peroxidation in lung cancer patients and can be assessed from the 8-isoprostane marker in overnight urine, with or without urine volume correction.

• Journal of Korean Biological Nursing Science
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• 제15권4호
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• pp.247-256
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• 2013

Purpose: This study aimed to determine the effects of listening to music on pain and vital signs of critically ill patients with ventilatory support in intensive care units during nursing treatment (changes of posture and tracheal suction). Methods: The experimental treatment was to use an mp3 player and a speaker to let them listen to classical music by Mozart during nursing treatment. To determine the effects of music intervention, pain (Critical-Care Pain Observation Tool-K) was used. The data analysis was carried out by using PASW Statistics 20.0. Results: Hypothesis "The scores for pain would differ between the experimental group provided with music intervention during nursing treatment, and the control group" was supported. Conclusion: Application of music intervention during nursing treatment for critically ill patients with ventilatory support in intensive care units was found to be effective in reducing pain. Therefore, music intervention during nursing treatment for critically ill patients with ventilatory support can be used as non-pharmaceutical nursing intervention to reduce pain for the patients.

• 한국임상약학회지
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• 제26권3호
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• pp.195-200
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• 2016

Background: Venous thromboembolism (VTE) is a common and life-threating condition in cancer patients. Low molecular weight heparins (LMWH), such as dalteparin, are recommended in the treatment of VTE. Also, rivaroxaban, an orally administered direct factor Xa inhibitor, was approved for the treatment of VTE. It showed similar efficacy to standard therapy (LMWH or warfarin) and was associated with significantly lower rates of major bleedings. However, in the real world, bleeding has been reported to occur frequently in cancer patient receiving rivaroxaban. The goal of this research was to analyze bleeding risks between rivaroxaban and dalteparin for treatment of VTE in cancer patients. Methods: Medical records of oncology patients who were treated with rivaroxaban or dalteparin for VTE from July 2012 to June 2014 were retrospectively reviewed. Data collected were as follows: age, sex, weight, height, cancer types and stages, ECOG (eastern cooperative oncology group) PS (performance score), VTE types, concurrently used medications, study drug information (dose and duration of therapy), INR (international normalized ratio), PT (prothrombin time), and platelet counts. Bleeding was classified into major bleedings, clinically relevant non-major bleedings, and minor bleedings. Results: A total of 399 patients were included in the study. Of these patients, 246 were treated with rivaroxaban and 153 with dalteparin. Bleeding rates were significantly higher in the rivaroxaban group than in the dalteparin group (adjusted odds ratio (AOR) 2.09, 95% CI 1.22-3.60) after adjusting for confounders. In addition, rivaroxaban remained independently associated with 1.78-fold (95% CI 1.14-2.76) shorter time to bleeding compared to dalteparin after adjusting other factors known to be associated with poor outcomes. Conclusion: This study suggested that rivaroxaban was associated with an increased risk of bleedings in cancer patients.

• 셀메드
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• 제4권2호
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• pp.10.1-10.8
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• 2014

Affecting more than half of menstruating women, dysmenorrhea is a cramp which causes abdominal or lower back pain just before or during a menstruation. In western medicine, non-steroidal anti-inflammatory drugs (NSAIDs) are normally used to treat primary dysmenorrheal symptoms. Despite their rapidity in relieving pain, NSAIDs have many serious side effects on the liver, kidney, and gastrointestinal tract. Thai traditional medicines comprise many preparations for treating dysmenorrhea, especially Prasaplai preparation which has been listed in the Thai traditional common household drug list since 2006. The use of Prasaplai was originated about 100 years ago and is still being used in the present time to treat dysmenorrhea. This review focuses on the history of the preparation, active ingredients, and biological activities especially on cyclooxygenase inhibitor, artifacts occurred in the preparation, quantitative analysis, and clinical trial of Prasaplai formulation.

• 셀메드
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• 제5권3호
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• pp.20.1-20.4
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• 2015

Ayurveda is often criticized for having empirical and non-evidence based approach to treat the patients. At the same time, modern medicine is also being criticized for having a non-holistic, reductionist and mechanistic approach of treating the patients which do not help in many real clinical situations. An open minded deduction of treatment approaches in both of these systems for a common patient however makes us to rethink that ideally both systems are similar with a common objective of offering a cure although in a manner which is better understood through their own methods of learning. The differences therefore, are more superficial rather than being deeply rooted in the understanding. A more tolerant viewpoint towards the competitive medical systems may therefore be a better approach to offer optimal health care to our people through a genuine amalgamation of these two health care sciences through an integrated approach. Once this tolerance is developed, it will give us an opportunity to think for a focused selection of type of health care depending upon the type of the disease and strength of the particular system in that area.

• Bulletin of the Korean Chemical Society
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• 제32권3호
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• pp.909-914
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• 2011

An improved convergent and economical method has been developed for the synthesis of erlotinib, a 4-anilinoquinazoline and an EGFR-tyrosine kinase inhibitor for treatment of non-small-cell lung cancer. The final two steps for the formation of this 4-anilinoquinazoline from suitable 2-aminobenzonitrile intermediate and 3-ethynylaniline were modified and were performed in a simple one-pot reaction. The ring-closing mechanism for the formation of erlotinib from the suitable formamidine intermediate and 3-ethynylaniline was investigated and determined to proceed via the formation of phenyl benzamidine intermediate rather than involving Dimroth rearrangement reported earlier. The new benzamidine intermediate was isolated for the first time and characterized.

• Archives of Pharmacal Research
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• 제9권2호
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• pp.81-86
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• 1986

The effect of imperatorin on hepatic microsomal mixed function oxidases (MF0) was investigated. On acute treatment, imperatorin (30 mg/kg, i.p) caused a significant reduction in activities of hepatic aminopyrine N-demethylase, hexobarbital hydroxylase and aniline hydroxylase as well as cytochrome p0450 content in rats and mice. Kinetic studies on rat liver enzymes revealed that imperatorin appeared to be a competitive inhibitor of aminopyrine N-demethylase (Ki,0.007 mM), whereas a non-competitive inhibitor of hexobarbital hydroxylase (Ki, 0.0148 mM). Imperatorin also inhibited non-competitively aniline metabolism (Ki 0.2 mM). Imperatorin binds to phenobarbital-induced cytochrome p-450 to give a typical type 1 binding sepctrum (max. 388nm, min 422 nm). Multiple administrations of imperatorin (30 mg/kg. i. p. daily for 7 days) to mice shortended markedly the duration of hexobarbital narcosis and increased activities of hepatic aminopyrine N-demethylase and hexobarbital hydroxylase and the level of cytochrome p-450 where as aniline hydroxylase activity was unaffected.

• Archives of Pharmacal Research
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• 제14권2호
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• pp.188-192
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• 1991

Single non-lethal doses of chloroform $(CHCL_3)$ dichlorobromomethane $(CHCL_2Br)$, dibromochloromethane $(CHCIBr_2)$, or bromoform $(CHBr_3)$ were administered to male rats. Routes of exposure including single intraperitional (ip) and subcutaneous (sc) injection were used in order to permit comparison of severity of THM effects and renal toxicity was assessed at varied times following treatment. On an equimolar basis, sc administration of $CHBr_3$ (either 12 or 3 mmoles/kg) is more effective at increasing KW/BW than ip $CHCI_3$ treatment. Plasma urea nitrogen (BUN) following ip THM injections are markedly increased with all four THM at 24 hours post treatment. BUN response to $CHCL_2Br$ and $CHCIBr_3$-effected BUN levels have essentially returned to those of vehicle control. THM sc treatment results in a BUN response similar to that seen following ip treatment, with only the time course being different. With the exception of $CHCL_3$, sc and ip-treatments appear to be equally effective in evoking absolute BUN elevations. These results suggest that THM administration induce renal toxicity dependent upon the route or exposure.

• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4391-4394
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• 2016

Background: Platinum-based regimens are effective treatments for advanced non-small cell lung cancer (NSCLC), but the five-year survival rate is still less than 20%. One possible factor appears to be resistance involving polymorphisms in the CTR1 gene which plays an importance role in accumulation of platinum in the cytoplasm. Purpose: To establish both prevalence of CTR1 polymorphism and its impact on treatment related toxicity in Thai advanced NSCLC patients. Materials and Methods: Thirty-two advanced NSCLC participants received carboplatin and gemcitabine during January to June 2016 at King Chulalongkorn Memorial Hospital (KCMH) were recruited for analysis of the CTR1 rs12686377 genotype. These participants were planning to be treated with platinum-based chemotherapy for at least two cycles. Results: Allele frequency of CTR1 polymorphism $G{\rightarrow}T$ was found to be 25%. The results showed that genetic polymorphism at CTR1 rs12686377 was associated with emesis side effects (P = 0.020) and neuropathic symptoms (P = 0.010). In addition, hematologic side effects in terms of anemia also tended to be related to this polymorphism. Conclusions: This is the first study suggesting that polymorphism at CTR1 rs12686377 may be associated with toxicity from platinum-based regimens. Therefore, it could be a factor to aid in treatment decision-making.