32 research outputs found
Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours
This study was undertaken to investigate the expression and predictive value for outcome of multidrug resistance-associated (MDR) proteins P-glycoprotein (Pgp), MRP1, BCRP, and LRP, in advanced testicular germ-cell tumours (TGCT). Paraffin-embedded sections from 56 previously untreated patients with metastatic TGCT were immunostained for Pgp, MRP1, BCRP, and LRP. All patients received platinum-based chemotherapy after orchidectomy. Immunostaining was related to clinicopathological parameters, response to chemotherapy, and outcome. Strong and intermediate expressions of the different MDR-related proteins were: 27 and 41% (Pgp), 54 and 37% (MRP1), 86 and 7% (BCRP), and 14 and 29% (LRP). P-glycoprotein and MRP1 associated, respectively, to low AFP (P=0.026) and high LDH levels (P=0.014), whereas LRP expression associated with high beta-hCG levels (P=0.003) and stage IV tumours (P=0.029). No correlation was found between Pgp, MRP1, and BCRP expression and response to chemotherapy and survival. In contrast, patients with LRP-positive tumours (strong or intermediate expression) had shorter progression-free (P=0.0006) and overall survival (P=0.0116) than LRP-negative patients, even after individual log-rank adjustments by statistically associated variables. Our data suggest that a positive LRP immunostaining at the time of diagnosis in metastatic TGCT is associated with an adverse clinical outcome
Effects of Dietary Restriction on Cancer Development and Progression
The effects of caloric restriction on tumor growth and progression are known for
over a century. Indeed, fasting has been practiced for millennia, but just recently
has emerged the protective role that it may exert toward cells. Fasting cycles are
able to reprogram the cellular metabolism, by inducing protection against oxidative
stress and prolonging cellular longevity. The reduction of calorie intake as
well as short- or long-term fasting has been shown to protect against chronic and
degenerative diseases, such as diabetes, cardiovascular pathologies, and cancer.
In vitro and in vivo preclinical models showed that different restriction dietary
regimens may be effective against cancer onset and progression, by enhancing
therapy response and reducing its toxic side effects. Fasting-mediated beneficial
effects seem to be due to the reduction of inflammatory response and downregulation
of nutrient-related signaling pathways able to modulate cell proliferation
and apoptosis. In this chapter, we will discuss the most significant studies
present in literature regarding the molecular mechanisms by which dietary
restriction may contribute to prevent cancer onset, reduce its progression, and
positively affect the response to the treatments
Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis
IntroductionObesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification.MethodsWe performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003–02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype.ResultsMultivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype.ConclusionsSeverely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes
Blood cell gene expression associated with cellular stress defense is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers
Background
Plant-based diets rich in fruit and vegetables can prevent development of several chronic age-related diseases. However, the mechanisms behind this protective effect are not elucidated. We have tested the hypothesis that intake of antioxidant-rich foods can affect groups of genes associated with cellular stress defence in human blood cells. Trial registration number: NCT00520819 http://clinicaltrials.gov.
Methods
In an 8-week dietary intervention study, 102 healthy male smokers were randomised to either a diet rich in various antioxidant-rich foods, a kiwifruit diet (three kiwifruits/d added to the regular diet) or a control group. Blood cell gene expression profiles were obtained from 10 randomly selected individuals of each group. Diet-induced changes on gene expression were compared to controls using a novel application of the gene set enrichment analysis (GSEA) on transcription profiles obtained using Affymetrix HG-U133-Plus 2.0 whole genome arrays.
Results
Changes were observed in the blood cell gene expression profiles in both intervention groups when compared to the control group. Groups of genes involved in regulation of cellular stress defence, such as DNA repair, apoptosis and hypoxia, were significantly upregulated (GSEA, FDR q-values < 5%) by both diets compared to the control group. Genes with common regulatory motifs for aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (AhR/ARNT) were upregulated by both interventions (FDR q-values < 5%). Plasma antioxidant biomarkers (polyphenols/carotenoids) increased in both groups.
Conclusions
The observed changes in the blood cell gene expression profiles suggest that the beneficial effects of a plant-based diet on human health may be mediated through optimization of defence processes
Optimal delivery of anthracycline-based chemotherapy in the adjuvant setting improves outcome of breast cancer patients
Screening of patients with augmented renal clearance in ICU: taking into account the CKD-EPI equation, the age, and the cause of admission
Comparison of Two NIRS Tissue Oximeters (Moxy and Nimo) for Non-Invasive Assessment of Muscle Oxygenation and Perfusion
BACKGROUND
Near-infrared spectroscopy (NIRS) tissue oximeters enable non-invasive measurement of muscle oxygenation and perfusion. Several NIRS oximeters are currently available, particularly for muscle measurements.
AIM
To evaluate the agreement of oxygenation and perfusion measurements obtained by two devices (Moxy, Fortiori Designs LLC, USA, and Nimo, Nirox, Italy) during an arterial occlusion test on the arm.
SUBJECT AND METHODS
Arterial occlusions were conducted at the arm of one individual for 10 min with 200 mmHg. Measurements were made twice a day on five different days. Both NIRS devices were fixed at the arm (covering the muscles extensor carpi ulnaris, extensor digitorum, and flexor carpi ulnaris).
RESULTS
The experiment revealed that i) both devices could detect changes in muscle oxygenation and perfusion during the occlusion, but ii) the magnitudes and dynamic changes differed between the two devices.
DISCUSSION AND CONCLUSION
Both devices had different performances with regard to the measurement of tissue oxygenation and perfusion. This study shows that it might be worthwhile to compare all NIRS tissue oximeters currently available for muscle measurement in a large systematic study to increase the comparability of measurements obtained with different devices
A central nervous system-focused treatment approach for people with frozen shoulder: protocol for a randomized clinical trial
Background: Frozen shoulder (FS) is a musculoskeletal condition of poorly understood etiology that results in shoulder pain and large mobility deficits. Despite some physical therapy interventions, such as joint mobilization and exercise, having shown therapeutic benefit, a definitive treatment does not currently exist. The aim of this study will be to compare the effectiveness of a central nervous system (CNS)-directed treatment program versus a standard medical and physical therapy care program on outcomes in participants with FS.
Methods/design: The study is a two-group, randomized clinical trial with blinding of participants and assessors. Participants will be recruited via referrals from orthopedic surgeons and physical therapists, community-based advertisements, private care practices and hospitals. Participants will be randomized to receive either a CNS-focused treatment program or standard medical and physical therapy care. The Shoulder Pain And Disability Index (SPADI) will be the primary outcome, while the Numeric Pain Rating Scale (NPRS), shoulder range of movement (ROM), The Patient Specific Functional Scale, two-point discrimination threshold and laterality judgement accuracy will be the secondary outcomes. Assessment will occur at baseline, at the end of the treatment program (week 10), and at 3 and 6 months' follow-up.
Discussion: Preliminary data suggest that treatments that target CNS function are a promising approach to the treatment of people with shoulder pain including patients with FS. In the context of modest effects from most available physical therapy treatments for FS, this CNS-focused approach may lead to improved clinical outcomes. The trial should determine if the CNS-directed program is more effective than traditional interventions at reducing pain intensity and improving function in a FS cohort and will follow up participants for 6 months, providing important information on the persistence of any treatment effects.This work is funded by the Conselleria de Educación, Investigación, Cultura y Deporte de la Generalitat Valenciana, Spain (GV/2016).Ye
Obesity Is More Strongly Associated With Inappropriate Eating Behaviors Than With Mental Health in Older Adults Receiving Congregate Meals
Glucose and Fructose Have Sugar-Specific Effects in Both Liver and Skeletal Muscle In Vivo: A Role for Liver Fructokinase
We examined glucose and fructose effects on serine phosphorylation levels of a range of proteins in rat liver and muscle cells. For this, healthy adult rats were subjected to either oral glucose or fructose loads. A mini-array system was utilized to determine serine phosphorylation levels of liver and skeletal muscle proteins. A glucose oral load of 125 mg/100 g body weight (G 1/2) did not induce changes in phosphorylated serines of the proteins studied. Loading with 250 mg/100 g body weight of fructose (Fr), which induced similar glycemia levels as G 1/2, significantly increased serine phosphorylation of liver cyclin D3, PI3 kinase/p85, ERK-2, PTP2 and clusterin. The G 1/2 increased serine levels of the skeletal muscle proteins cyclin H, Cdk2, IRAK, total PKC, PTP1B, c-Raf 1, Ras and the β-subunit of the insulin receptor. The Fr induced a significant increase only in muscle serine phosphorylation of PI3 kinase/p85. The incubation of isolated rat hepatocytes with 10 mM glucose for 5 min significantly increased serine phosphorylation of 31 proteins. In contrast, incubation with 10 mM fructose produced less intense effects. Incubation with 10 mM glucose plus 75 µM fructose counteracted the effects of the incubation with glucose alone, except those on Raf-1 and Ras. Less marked effects were detected in cultured muscle cells incubated with 10 mM glucose or 10 mM glucose plus 75 µM fructose. Our results suggest that glucose and fructose act as specific functional modulators through a general mechanism that involves liver-generated signals, like micromolar fructosemia, which would inform peripheral tissues of the presence of either glucose- or fructose-derived metabolites