Escaping death: Mitochondrial redox homeostasis in cancer cells

Reactive oxygen species (ROS) are important signaling molecules that act through the oxidation of nucleic acids, proteins, and lipids. Several hallmarks of cancer, including uncontrolled proliferation, angiogenesis, and genomic instability, are promoted by the increased ROS levels commonly found in tumor cells. To counteract excessive ROS accumulation, oxidative stress, and death, cancer cells tightly regulate ROS levels by enhancing scavenging enzymes, which are dependent on the reducing cofactor nicotinamide adenine dinucleotide phosphate (NADPH). This review focuses on mitochondrial ROS homeostasis with a description of six pathways of NADPH production in mitochondria and a discussion of the possible strategies of pharmacological intervention to selectively eliminate cancer cells by increasing their ROS levels

Spatial Olfactory Memory and Spatial Olfactory Navigation, Assessed with a Variant of Corsi Test, Is Modulated by Gender and Sporty Activity

Many studies have focused on navigation, spatial skills, and the olfactory system in comparative models, including those concerning the relationship between them and physical activity. Although the results are often in contrast with each other, it is assumed that physical activity can affect cognition in different ways-both indirectly and through a certain influence on some brain structures. In contrast, there is little research that focuses on the relationship between spatial abilities and olfactory abilities in humans. This research aimed to evaluate and compare the performance in working memory tasks of athletes and non-athletes who require good visual-spatial navigation, olfactory-spatial navigation, and olfactory-semantic skills. The study involved 236 participants (83 athletes) between the ages of 18 and 40. All subjects were matched by age or sex. The standard Corsi Block Tapping Test (CBTT) was administrated to investigate the visual-spatial memory. Olfactory-spatial navigation and olfactory-semantic skills were assessed with two modified versions of CBTT: Olfactory CBTT (OCBTT) and Semantic-Olfactory CBTT (SOCBTT) respectively. The results show differences between the CORSI conditions in direction of a poor performance for athletes. A gender effect in favor of men was also found, particularly in the classic version of the CBTT. Both groups performed better in the classic version of the CBTT than OCBTT and SOCBTT. The mean of SOCBTT results is markedly lower, perhaps due to the different information processing systems needed to perform this kind of task. It is possible to explain how sports practice can affect tasks that require spatial skills and olfactory perception differently, thus supporting new hypotheses and opening new scientific horizons

intravenous versus oral vinorelbine plus capecitabine as second line treatment in advanced breast cancer patients a retrospective comparison of two consecutive phase ii studies

Abstract Vinorelbine (i.v.) plus capecitabine (oral) combination therapy is active in anthracycline/taxane pretreated patients with metastatic breast cancer. Availability of oral vinorelbine provides this combination in an all-oral formulation. Two consecutive phase II trials differing only in vinorelbine administration routes evaluated their respective activities and tolerabilities in this population. In the i.v. group ( n = 38) disease control was 61% (37% PR, 24% SD), median TTP 6.8 months and median survival 11.3 months. In the oral group ( n = 38) disease control was 77% (5.4% CR, 34% PR, 38% SD), median TTP 7 months and median survival 10 months. G3–G4 neutropenia was more common in the oral group (

Chemosensory Event-Related Potentials and Power Spectrum could be A Possible Biomarker in 3M Syndrome Infants?

none10no3M syndrome is a rare disorder that involves the gene cullin-7 (CUL7). CUL7 modulates odour detection, conditions the olfactory response (OR) and plays a role in the development of the olfactory system. Despite this involvement, there are no direct studies on olfactory functional effects in 3M syndrome. The purpose of the present work was to analyse the cortical OR through chemosensory event-related potentials (CSERPs) and power spectra calculated by electroencephalogram (EEG) signals recorded in 3M infants: two twins (3M-N) and an additional subject (3M-O). The results suggest that olfactory processing is diversified. Comparison of N1 and Late Positive Component (LPC) indicated substantial differences in 3M syndrome that may be a consequence of a modified olfactory processing pattern. Moreover, the presence of delta rhythms in 3M-O and 3M-N clearly indicates their involvement with OR, since the delta rhythm is closely connected to chemosensory perception, in particular to olfactory perception.openInvitto, Sara; Grasso, Alberto; Lofrumento, Dario Domenico; Ciccarese, Vincenzo; Paladini, Angela; Paladini, Pasquale; Marulli, Raffaella; Pascalis, Vilfredo De; Polsinelli, Matteo; Placidi, GiuseppeInvitto, Sara; Grasso, Alberto; Lofrumento, Dario Domenico; Ciccarese, Vincenzo; Paladini, Angela; Paladini, Pasquale; Marulli, Raffaella; Pascalis, Vilfredo De; Polsinelli, Matteo; Placidi, Giusepp

Potential Role of OERP as Early Marker of Mild Cognitive Impairment

Olfactory impairment is present in up to 90% of patients with Alzheimer’s disease (AD) and is present in certain cases of mild cognitive impairment (MCI), a transient phase between normal aging and dementia. Subjects affected by MCI have a higher risk of developing dementia compared to the general population, and studies have found that olfactory deficits could be an indicator of whether such a conversion might happen. Following these assumptions, aim of this study was to investigate olfactory perception in MCI patients. We recruited 12 MCI subjects (mean age 70 ± 6.7 years) through the Alzheimer Assessment Unit (UVA Unite) of ASL Lecce (Italy), and 12 healthy geriatric volunteers (HS) as the control group (mean age 64 ± 6.0 years), all of whom were first evaluated via a panel of neuropsychological tests. Subjects were asked to perform an olfactory recognition task involving two scents: rose and eucalyptus, administrated in the context of an oddball task during EEG recordings. Olfactory event-related potential (OERP) components N1 and Late Positive Potential (LPC) were then analyzed as measures of the sensorial and perceptive aspects of the olfactory response, respectively. It was determined that, in the MCI group, both the N1 and LPC components were significantly different compared to those of the HS group during the execution of the oddball task. In particular, the N1 amplitude, was reduced, while the LPC amplitude was increased, indicating that a degree of perceptive compensation can occur when sensorial function is impaired. Further, a correlation analysis, involving OERP components and neuropsychological battery scores, indicated that impairment of olfactory perception may share common pathways with impairments of the spatial system and long-term memory processing

Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Escaping Death: Mitochondrial Redox Homeostasis in Cancer Cells

Reactive oxygen species (ROS) are important signaling molecules that act through the oxidation of nucleic acids, proteins, and lipids. Several hallmarks of cancer, including uncontrolled proliferation, angiogenesis, and genomic instability, are promoted by the increased ROS levels commonly found in tumor cells. To counteract excessive ROS accumulation, oxidative stress, and death, cancer cells tightly regulate ROS levels by enhancing scavenging enzymes, which are dependent on the reducing cofactor nicotinamide adenine dinucleotide phosphate (NADPH). This review focuses on mitochondrial ROS homeostasis with a description of six pathways of NADPH production in mitochondria and a discussion of the possible strategies of pharmacological intervention to selectively eliminate cancer cells by increasing their ROS levels