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Molecular mechanisms of natural compounds in cell death induction and sensitization to chemotherapeutic drugs in lung cancer.
Wattanathamsan, O, Hayakawa, Y, Pongrakhananon, V
Phytotherapy research : PTR. 2019;(10):2531-2547
Abstract
Cancer remains one of the leading causes of death worldwide, especially lung cancer. Chemotherapeutic drugs are commonly used for lung cancer treatment; nonetheless, undesirable side effects and drug resistance remain major challenges for therapeutic success. Therefore, harmless and effective treatments against lung cancer are urgently required. The use of natural phytochemical products, in single or combinatorial therapy, is an emerging strategy for prevention and cure of cancer because of the various remarkable anticancer properties of these compounds. Cell death, which primarily occurs via apoptosis and nonapoptotic mechanisms (necrosis, autophagy, and cellular senescence), is one of the antineoplastic effects of natural compounds. In this review, we highlight representative plant-derived compounds with cancer chemopreventive and sensitizing effects in combination with chemotherapeutic drugs with various cell death-inducing mechanisms. Relevant molecular mechanisms implicated in the pharmacological effects of these natural compounds are discussed. Overall, this review provides a reference and new perspective for application of phytochemical agents as potential anti-lung cancer drugs for further cancer drug research and development.
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The Effects of Dietary Supplements on Asthma and Lung Cancer Risk in Smokers and Non-Smokers: A Review of the Literature.
Alsharairi, NA
Nutrients. 2019;(4)
Abstract
Smoking is one of the major global causes of death. Cigarette smoke and secondhand (passive) smoke have been causally related to asthma and lung cancer. Asthma is a potential risk factor for developing lung cancer in both smokers and non-smokers. Prospective studies and randomized control trials (RCTs) of dietary supplements and lung cancer risk in adult smokers and non-smokers have yielded inconsistent results. A few prospective studies have shown that long-term use of high doses of some supplements, such as retinol, β-carotene, B vitamins, and vitamin E, increase lung cancer risk in current and former smokers. Limited evidence from RCTs suggests that vitamin D supplementation is effective in improving lung function and reducing asthma risk in current/former smokers. The relationship between dietary supplements and lung cancer risk has never before been examined in asthmatic smokers and non-smokers. This short review aims to examine the evidence from existing studies for the effects of dietary supplements on asthma/lung cancer risk and mortality in smokers and non-smokers.
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Hydrogen bond analysis of the EGFR-ErbB3 heterodimer related to non-small cell lung cancer and drug resistance.
Ghosh, A, Yan, H
Journal of theoretical biology. 2019;:63-71
Abstract
Lung cancer is the predominant cause of cancer deaths on a worldwide scale. A mutation in the epidermal growth factor receptor (EGFR) can cause non-small cell lung cancer (NSCLC). The L858R one-point mutation in exon 21 in EGFR is the most prevalent in NSCLC. For over 60% of EGFR-muted NSCLC, another mutation T790M can cause drug resistance. In this paper, we consider EGFR and ErbB3 heterodimers involving three structures of EGFR, wild-type, with L858R mutation, and with L858R and T790M mutations. We perform molecular dynamics (MD) simulations to analyze hydrogen bonds in all three instances. The hydrogen bonds contribute to the conformational stability of the protein and molecular recognition. Several other parameters are also investigated in the present study, which reveals significant changes in the dimer at different levels of mutation. The knowledge and results obtained from this study lead to useful insight into the mechanism of NSCLC drug resistance.
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Acquired haemophilia A in a patient with breast cancer and lung carcinoma: a case report and literature review.
Biesheuvel, V, Hiddema, SM, Levenga, H, Eikenboom, J, van der Deure, WM
The Netherlands journal of medicine. 2019;(4):153-155
Abstract
Acquired haemophilia A is a rare disorder caused by spontaneous formation of auto-antibodies (inhibitors) against coagulation factor VIII. This can lead tolife-threatening haemorrhages. Six to twenty-two percent of patients with acquired haemophilia have an underlying malignancy. We describe a 69-year-old woman with metastatic breast cancer and non-small cell lung carcinoma who presented at the emergency room with spontaneous bruising, and who was using a vitamin K antagonist. She had a prolonged activated partial thromboplastin time (aPTT) due to a coagulation factor VIII deficiency caused by factor VIII antibodies. She was treated with prednisone and cyclophosphamide.
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Mechanistic Understanding of Curcumin's Therapeutic Effects in Lung Cancer.
Wan Mohd Tajuddin, WNB, Lajis, NH, Abas, F, Othman, I, Naidu, R
Nutrients. 2019;(12)
Abstract
Lung cancer is among the most common cancers with a high mortality rate worldwide. Despite the significant advances in diagnostic and therapeutic approaches, lung cancer prognoses and survival rates remain poor due to late diagnosis, drug resistance, and adverse effects. Therefore, new intervention therapies, such as the use of natural compounds with decreased toxicities, have been considered in lung cancer therapy. Curcumin, a natural occurring polyphenol derived from turmeric (Curcuma longa) has been studied extensively in recent years for its therapeutic effects. It has been shown that curcumin demonstrates anti-cancer effects in lung cancer through various mechanisms, including inhibition of cell proliferation, invasion, and metastasis, induction of apoptosis, epigenetic alterations, and regulation of microRNA expression. Several in vitro and in vivo studies have shown that these mechanisms are modulated by multiple molecular targets such as STAT3, EGFR, FOXO3a, TGF-β, eIF2α, COX-2, Bcl-2, PI3KAkt/mTOR, ROS, Fas/FasL, Cdc42, E-cadherin, MMPs, and adiponectin. In addition, limitations, strategies to overcome curcumin bioavailability, and potential side effects as well as clinical trials were also reviewed.
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Dietetic assessment and intervention in lung cancer.
Phillips, I, Hug, A, Allan, L, Ezhil, V
Current opinion in supportive and palliative care. 2019;(4):311-315
Abstract
PURPOSE OF REVIEW Systemic therapy for lung cancer is increasing in intensity and duration. European nutrition guidelines suggest screening for weight loss and malnutrition, however acknowledges there is a lack of evidence. We discuss current data round this issue and identify opportunities for further research. RECENT FINDINGS International guidelines now exist to aid the definition of weight loss in cancer, including cachexia, sarcopenia and malnutrition. These allow consistent definition of overlapping, but distinct clinical syndromes. Nutritional status can be assessed in a range of ways including questionnaires, functional assessments, blood markers, physical activity, weight and BMI. Weight loss is commonly associated with a proinflammatory state. Future treatment is likely to be a combination of dietetic support and pharmacological treatment of cachexia. SUMMARY There is a paucity of data on dietetic intervention. It is potentially quick, inexpensive and patient specific, using a holistic approach to aid patients who are malnourished or at risk of malnutrition. Lung cancer-related weight loss is common, further strategies are needed to effectively assess and intervene. Dietetic intervention has the potential to improve patients' quality of life and outcomes.
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Delivery of natural phenolic compounds for the potential treatment of lung cancer.
Muller, AG, Sarker, SD, Saleem, IY, Hutcheon, GA
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences. 2019;(1):433-449
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Abstract
The application of natural products to treat various diseases, such as cancer, has been an important area of research for many years. Several phytochemicals have demonstrated anticarcinogenic activity to prevent or reduce the progression of cancer by modulating various cellular mechanisms. However, poor bioavailability has hindered clinical success and the incorporation of these drugs into efficient drug delivery systems would be beneficial. For lung cancer, local delivery via the pulmonary route would also be more effective. In this article, recent in vitro scientific literature on phenolic compounds with anticancer activity towards lung cancer cell lines is reviewed and nanoparticulate delivery is mentioned as a possible solution to the problem of bioavailability. The first part of the review will explore the different classes of natural phenolic compounds and discuss recent reports on their activity on lung cancer cells. Then, the problem of the poor bioavailability of phenolic compounds will be explored, followed by a summary of recent advances in improving the efficacy of these phenolic compounds using nanoparticulate drug delivery systems. Graphical abstract The rationale for direct delivery of phenolic compounds loaded in microparticles to the lungs.
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Integrin as a Molecular Target for Anti-cancer Approaches in Lung Cancer.
Aksorn, N, Chanvorachote, P
Anticancer research. 2019;(2):541-548
Abstract
Integrins are cell-matrix adhesion molecules providing both mechanical engagement of cell to extracellular matrix, and generation of cellular signals that are implicated in cancer malignancies. The concept that integrins play important roles in cell survival, proliferation, motility, differentiation, and ensuring appropriate cell localization, leads to the hypothesis that inhibition of certain integrins would benefit cancer therapy. In lung cancer, integrins αv, α5, β1, β3, and β5 have been shown to augment survival and metastatic potential of cancer cells. This review presents data suggesting integrins as molecular targets for anti-cancer approaches, and the mechanisms through which integrins confer resistance of lung cancer to chemotherapeutics and metastasis. The better understanding of these key molecules may benefit the discovery of anti-cancer drugs and strategies.
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Late-onset chylothorax during chemotherapy after lobectomy for lung cancer: A case report and review of the literature.
Zhang, C, Zhang, RM, Pan, Y, Wu, WB, Zhang, M
Medicine. 2019;(22):e15909
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Abstract
RATIONALE Chylothorax is usually diagnosed within a few days after lobectomy. Late-onset chylothorax following trauma or thoracic surgery is rare but potentially lethal, lacking reliable preventive methods. PATIENT CONCERNS A 54-year-old male patient complained of dyspnea during adjuvant chemotherapy on the 35th postoperative day after right middle lobectomy and systemic lymph node dissection (SLND) for lung cancer. His computed tomography indicated massive pleural effusion filling in the right chest cavity. DIAGNOSES The patient was primarily diagnosed as late-onset chylothorax, without definite evidence to exclude spontaneous chylous leakage. INTERVENTIONS Uniportal video-assisted thoracoscopic thoracic duct ligation (TDL) was performed for him, as conservative treatment using octreotide with fat-free diet turned out to be ineffective. OUTCOMES His pleural effusion was gradually diminished after reoperation, and the patient was discharged 9 days after TDL. LESSONS Postoperative late-onset or spontaneous chylothorax should be kept in mind after pulmonary resection and SLND, and the exclusion of chylous leakage could be considered as a precondition of chest tube removal.
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The Associations of Fruit and Vegetable Intake with Lung Cancer Risk in Participants with Different Smoking Status: A Meta-Analysis of Prospective Cohort Studies.
Wang, C, Yang, T, Guo, XF, Li, D
Nutrients. 2019;(8)
Abstract
The results of epidemiological studies on the relationship between fruit and vegetable intake and lung cancer risk were inconsistent among participants with different smoking status. The purpose of this study was to investigate these relationships in participants with different smoking status with prospective cohort studies. A systematic literature retrieval was conducted using PubMed and Scopus databases up to June 2019. The summary relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were calculated by random-effects model. The nonlinear dose-response analysis was carried out with restricted cubic spline regression model. Publication bias was estimated using Begg's test. Nine independent prospective studies were included for data synthesis. Dietary consumption of fruit was negatively correlated with lung cancer risk among current smokers and former smokers, and the summery RRs were 0.86 (95% CI: 0.78, 0.94) and 0.91 (95% CI: 0.84, 0.99), respectively. Consumption of vegetable was significantly associated with reduced risk of lung cancer for current smokers (summary RR = 87%; 95% CI: 0.78, 0.94), but not for former smokers and never for smokers. Dose-response analysis suggested that risk of lung cancer was reduced by 5% (95% CI: 0.93, 0.97) in current smokers, and reduced by 4% (95% CI: 0.93, 0.98) in former smokers with an increase of 100 grams of fruit intake per day, respectively. Besides, dose-response analysis indicated a 3% reduction in lung cancer risk in current smokers for 100 gram per day increase of vegetable intake (95% CI: 0.96, 1.00). The findings of this study provide strong evidence that higher fruit consumption is negatively associated with the risk of lung cancer among current smokers and former smokers, while vegetable intake is significantly correlated with reducing the risk of lung cancer in current smokers. These findings might have considerable public health significance for the prevention of lung cancer through dietary interventions.