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1.
Curing breast cancer and killing the heart: A novel model to explain elevated cardiovascular disease and mortality risk among women with early stage breast cancer.
Kirkham, AA, Beaudry, RI, Paterson, DI, Mackey, JR, Haykowsky, MJ
Progress in cardiovascular diseases. 2019;(2):116-126
Abstract
Due to advances in prevention, early detection and treatment, early breast cancer mortality has decreased by nearly 40% during the last four decades. Yet, the risk of cardiovascular disease (CVD) mortality is significantly elevated following a breast cancer diagnosis, and it is a leading cause of death in this population. This review will discuss the most recent evidence for risks, pathology, mechanisms, and prevention of CVD morbidity and mortality in women with breast cancer. This evidence will be synthesized into a new model 'the compounding risk and protection model.' This model proposes that the balance between risk factors (i.e., older age, pre-existing traditional CVD risk factors and shared biologic pathways for CVD and cancer such as inflammation, as well as treatment-related and lifestyle toxicity) and potential protection factors (i.e., lifelong non-smoking, regular physical activity, a healthy diet rich in fruits and vegetables, and management of body weight and stress, heart failure therapy) determine the individual risk of CVD morbidity and mortality after diagnosis of early breast cancer.
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2.
Successful Control of Dasatinib-related Chylothorax by the Japanese Herbal Medicine "Goreisan".
Sasaki, H, Kimizuka, Y, Ogata, H, Okada, Y, Ota, S, Sano, T, Watanabe, C, Maki, Y, Yamamoto, T, Tagami, Y, et al
Internal medicine (Tokyo, Japan). 2019;(21):3139-3141
Abstract
Dasatinib-related chylothorax is a rare adverse event, and the mechanism underlying its occurrence is still not fully understood. We herein report the case of a 73-year-old woman with chronic myeloid leukemia (CML) who developed dasatinib-related chylothorax refractory to conventional treatments, except for steroids. To the best of our knowledge, this is the first case of dasatinib-related chylothorax which was successfully controlled by combining diuretics with the Japanese herbal medicine "Goreisan." "Goreisan" is known to inhibit aquaporin channels and regulate the water flow. Our findings showed that "Goreisan" is an effective treatment option for uncontrollable dasatinib-related chylothorax.
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Identifying and targeting cancer-specific metabolism with network-based drug target prediction.
Pacheco, MP, Bintener, T, Ternes, D, Kulms, D, Haan, S, Letellier, E, Sauter, T
EBioMedicine. 2019;:98-106
Abstract
BACKGROUND Metabolic rewiring allows cancer cells to sustain high proliferation rates. Thus, targeting only the cancer-specific cellular metabolism will safeguard healthy tissues. METHODS We developed the very efficient FASTCORMICS RNA-seq workflow (rFASTCORMICS) to build 10,005 high-resolution metabolic models from the TCGA dataset to capture metabolic rewiring strategies in cancer cells. Colorectal cancer (CRC) was used as a test case for a repurposing workflow based on rFASTCORMICS. FINDINGS Alternative pathways that are not required for proliferation or survival tend to be shut down and, therefore, tumours display cancer-specific essential genes that are significantly enriched for known drug targets. We identified naftifine, ketoconazole, and mimosine as new potential CRC drugs, which were experimentally validated. INTERPRETATION The here presented rFASTCORMICS workflow successfully reconstructs a metabolic model based on RNA-seq data and successfully predicted drug targets and drugs not yet indicted for colorectal cancer. FUND This study was supported by the University of Luxembourg (IRP grant scheme; R-AGR-0755-12), the Luxembourg National Research Fund (FNR PRIDE PRIDE15/10675146/CANBIO), the Fondation Cancer (Luxembourg), the European Union's Horizon2020 research and innovation programme under the Marie Sklodowska- Curie grant agreement No 642295 (MEL-PLEX), and the German Federal Ministry of Education and Research (BMBF) within the project MelanomSensitivity (BMBF/BM/7643621).
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Sorafenib treatment on Chinese patients with advanced hepatocellular carcinoma: A study on prognostic factors of the viral and tumor status.
Lee, SW, Lee, TY, Peng, YC, Yang, SS, Yeh, HZ, Chang, CS
Medicine. 2019;(44):e17692
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Abstract
Sorafenib is of proven efficacy in treating patients of hepatocellular carcinoma (HCC). Our study was aimed to determine the factors influence the sorafenib efficacy.We evaluated data of HCC patients receiving sorafenib from June 2012 to October 2016. All HCC cases were of the Barcelona Clinic Liver Cancer (BCLC) classification stage C. The exclusion criteria: those of BCLC classification stage A or B, with the absence or co-infection of hepatitis B (HBV) and hepatitis C (HCV). The presence of HBV, HCV, macoscopic vascular invasion (MVI) or extrahepatic spread (EHS) was recorded for each patient. Time-to-progression (TTP) and overall survival (OS) were analyzed.Among a total of 90 HCC patients, 48 (53.3%) had HBV infection, 42 (46.7%) had HCV infection, 51 (56.7%) had MVI, and 39 (43.3%) had EHS. Patients with HCV infection showed better TTP and OS than those with HBV infection. Patients with EHS had a longer TTP and OS than those with MVI. For patients with HBV infection, those with EHS had a longer TTP (mean 4.60 vs 2.64 months, P = .002) and OS (mean 6.65 vs 4.53 months, P = .045) compared to those with MVI. Among those with MVI, patients with HBV infection had a poorer TTP (mean 2.64 vs 4.74 months, P = .019) and shorter OS (mean 4.53 vs 7.00 months, P = .059) compared to those with HCV infection.HCC patients with HCV infection or with the presence of EHS showed better sorafenib efficacy.
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A Pilot Study of Amino Acids in Unresectable Non-Small-Cell Lung Cancer Patients During Chemotherapy: A Randomized Serial N-of-1 Trials Design.
Liu, L, Zhang, Y, Wei, J, Chen, Z, Yu, J
Nutrition and cancer. 2019;(3):399-408
Abstract
The aim of this study was to evaluate the effect of amino acids (AAs) on immune function and inflammation level in patients with NSCLC receiving chemotherapy. We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing AAs with isocaloric glucose in unresectable NSCLC patients and combined the individual results using Bayesian statistical modeling. 25 patients completed two cycles of chemotherapy. The baseline total blood albumin (ALB) level in all patients was 28 ± 3.3 g/l, and the mean total ALB level in patients receiving AAs supplementation and isocaloric glucose was 29.2 ± 2.2 and 28.1 ± 3.7 g/l, respectively (P = 0.028). Patients' baseline C-reactive protein (CRP) level was 4 ± 1.2 mg/l, the mean total CRP level in patients receiving AAs supplementation and isocaloric glucose was 11 ± 2.8 and 13 ± 3.2 mg/l, respectively (P = 0.028). The baseline total blood CD4+ T cells level was 36 ± 7.8%. The percentage of CD4+ T cells in patients receiving AAs supplementation and isocaloric glucose was 42 ± 6.4 and 33.7 ± 17.3, respectively (P = 0.034). Our preliminary results indicated that AAs improve immune status and suppress inflammation in unresectable NSCLC patients receiving chemotherapy.
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Cyclooxygenase (COX) Inhibition by Acetyl Salicylic Acid (ASA) Enhances Antitumor Effects of Nitric Oxide in Glioblastoma In Vitro.
Guenzle, J, Garrelfs, NWC, Goeldner, JM, Weyerbrock, A
Molecular neurobiology. 2019;(9):6046-6055
Abstract
Glioblastoma multiforme (GBM) is the most aggressive brain tumor with a high recurrence rate and a median survival of about 16 months even with multimodal therapy. Novel experimental strategies against malignant gliomas include cyclooxygenase (COX) inhibition and nitric oxide (NO)-based therapies. Therapeutic doses of NO can be delivered to tumor cells by NO donors such as JS-K (O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate) which releases NO upon enzymatic activation by glutathione S-transferase. COX-2 is frequently overexpressed in tumors and increases tumor invasiveness and angiogenesis. In this study, we show that pretreatment with acetyl salicylic acid (ASA) enhanced the cytotoxic antitumor effect of NO in vitro. Combination of low doses of JS-K and ASA revealed a dose-dependent synergistic increase of necrotic cell death under circumvention of classical apoptosis and alteration of the metabolic calcium level. These findings provide an opportunity to improve currently used therapeutic strategies in the treatment of gliomas with a well-established remedy.
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The inflammation-reducing compatible solute ectoine does not impair the cytotoxic effect of ionizing radiation on head and neck cancer cells.
Rieckmann, T, Gatzemeier, F, Christiansen, S, Rothkamm, K, Münscher, A
Scientific reports. 2019;(1):6594
Abstract
Ectoine is a natural protectant expressed by halophile bacteria to resist challenges of their natural environments, such as drought, heat or high salt concentrations. As a compatible solute, ectoine does not interfere with the cell's metabolism even at high molar concentrations. External application of ectoine results in surface hydration and membrane stabilization. It can reduce inflammation processes and was recently tested in a pilot study for the prevention and treatment of chemotherapy-induced oral mucositis. Oral mucositis is especially frequent and severe in patients with head and neck squamous cell carcinoma (HNSCC), who receive radiotherapy or chemoradiation. It is extremely painful, can limit nutritional intake and may necessitate treatment interruptions, which can critically compromise outcome. As it was recently reported that in vitro ectoine has the ability to protect DNA against ionizing irradiation, it was the aim of this study to test whether ectoine may protect HNSCC cells from radiotherapy. Using HNSCC cell lines and primary human fibroblasts, we can show that in living cells ectoine does not impair DNA damage induction and cytotoxicity through ionizing radiation. We therefore conclude that testing the ectopic application of ectoine for its ability to alleviate early radiotherapy/chemoradiation-induced side effects is safe and feasible.
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Efficacy and toxicity of eribulin treatment in metastatic breast cancer patients.
Brems-Eskildsen, AS, Kristoffersen, KB, Linnet, S, Lörincz, T, Langkjer, ST
Acta oncologica (Stockholm, Sweden). 2019;(1):119-121
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Food habits during treatment of childhood cancer: a critical review.
Beaulieu-Gagnon, S, Bélanger, V, Marcil, V
Nutrition research reviews. 2019;(2):265-281
Abstract
Several factors can affect the nutritional status of children undergoing cancer therapy. The present review aims to describe children's food intake during cancer treatments and to explore the contributing determinants. It also assesses the nutritional educational interventions developed for this clientele. Scientific literature from January 1995 to January 2018 was searched through PubMed and MEDLINE using keywords related to childhood cancer and nutritional intake. Quantitative and qualitative studies were reviewed: forty-seven articles were selected: thirty-eight related to food intake and parental practices and nine related to nutritional interventions. Patients' intakes in energy, macronutrients and micronutrients were compared with those of healthy controls or with requirement standards. Generally, patients ate less energy and proteins than healthy children, but adhered similarly to national guidelines. There is a lack of consensus for standard nutrient requirement in this population and a need for more prospective evaluations. Qualitative studies provide an insight into the perceptions of children, parents and nurses on several determinants influencing eating behaviours, including the type of treatment and their side effects. Parental practices were found to be diverse. In general, savoury and salty foods were preferred to sweet foods. Finally, most interventional studies in childhood cancer have presented their protocol or assessed the feasibility of an intervention. Therefore, because of the variability of study designs and since only a few studies have presented results, their impact on the development of healthful eating habits remains unclear. A better understanding of children's nutritional intakes and eating behaviours during cancer treatment could guide future nutritional interventions.
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The performance of three oncogeriatric screening tools - G8, optimised G8 and CARG - in predicting chemotherapy-related toxicity in older patients with cancer. A prospective clinical study.
Kotzerke, D, Moritz, F, Mantovani, L, Hambsch, P, Hering, K, Kuhnt, T, Yahiaoui-Doktor, M, Forstmeyer, D, Lordick, F, Knödler, M
Journal of geriatric oncology. 2019;(6):937-943
Abstract
BACKGROUND Older patients are vulnerable to chemotherapy-related toxicity (CRT). Therefore we evaluated screening tools in their power to predict CRT. METHODS Patients with cancer aged ≥65 years completed three screening questionnaires (G8, optimised G8 and Cancer and Ageing Research Group (CARG). Additionally, Comprehensive geriatric assessment (CGA) for verification of supportive care needs was undertaken on patients with impaired G8 scores. During chemotherapy treatment patients were assessed, capturing grade 0-5 CRT as defined by NCI CTCAE 4. RESULTS 104 patients with non-haematological cancers were included at three study sites. Median age was 73 years (range 65-85). Onco-geriatric screening detected 74% as impaired using G8 and optimised G8 questionnaires and 86% using CARG screening. Grade 3-5 toxicity affected 64.4% of all patients. G8 (OR 0.3 95% CI [0.1;1.0]) and optimised G8 (OR 0.4 95% CI [0.1; 1.5]) did not reliably predict CRT, whereas screening with CARG demonstrated a strong prediction of severe CRT: OR 4.2, 95% CI [1.1, 15.9]. CGA was undertaken on 66 patients, revealing deficiencies in nutritional (83%) and functional-status (54%) and occurrence of relevant comorbidity (53%). CONCLUSION The CARG tool could be useful for predicting CRT. CGA showed clinically relevant supportive care needs in patients with a positive G8 screening.