Longevity: Lesson from model organisms

Research on longevity and healthy aging promises to increase our lifespan and decrease the burden of degenerative diseases with important social and economic effects. Many aging theories have been proposed, and important aging pathways have been discovered. Model organisms have had a crucial role in this process because of their short lifespan, cheap maintenance, and manipulation possibilities. Yeasts, worms, fruit flies, or mammalian models such as mice, monkeys, and recently, dogs, have helped shed light on aging processes. Genes and molecular mechanisms that were found to be critical in simple eukaryotic cells and species have been confirmed in humans mainly by the functional analysis of mammalian orthologues. Here, we review conserved aging mechanisms discovered in different model systems that are implicated in human longevity as well and that could be the target of anti-aging interventions in human

Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study.

BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showed mutations in 43% (68/160) of the cases, while mutation analyses of exon 2 of the Ki-ras gene showed mutations in 46% (74/160) of the cases. Multivariate analyses showed that clinical outcome were strongly associated with the presence of specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13. CONCLUSION: Specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic CRC

Association between Hashimoto's thyroiditis and papillary thyroid carcinoma: A retrospective analysis of 305 patients

Background: The association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) is a controversial question that is still under debate, its pathological significance and the eventual clinical implications of this association remaining unclear. Methods: The data regarding 305 patients were retrospectively analyzed. The patients were divided in two different groups. A first group made up of 142 patients undergoing surgery for differentiated thyroid carcinoma was compared to a control group of 142 analogous subjects operated for normofunctioning goiter. A second group was made up of 163 patients who had undergone total thyroidectomy (TT) with pre-operative diagnosis of HT. Results: In the first group of patients an association with HT was found in 28,6% of the patients with final histopathological diagnosis of PTC versus 7,7% of the patients with histopathological diagnosis of multinodular goiter, which was a significant difference (p < 0.001). In the second group, the association with PTC was found in 43 (40,2%) cases of HT nodular variant and in 3 cases (8,1%) of HT diffuse variant (p < 0.001). Conclusions: The relationship between HT and PTC is still far from clear and represents an unresolved issue. Our own study has underlined the frequent coexistence of these two pathologies, an aspect not to be neglected in clinical practice. Patients receiving HT diagnosis should undergo careful follow-up and, especially those with the nodular variant, should undergo a frequent both clinical and cytological evaluation of the nodular lesions, taking always into great consideration the surgical approach of total thyroidectomy

Validity of needle core biopsy in the histological characterisation of mammary lesions

Over the last few years, there has been an enormous increase in the use of needle core biopsy (CB) for the histopathological characterisation of suspect lesions of the breast. The aim of this study was to verify the diagnostic reliability of CB by comparing the histological results obtained with the use of this technique with those obtained from the whole of the surgically resected specimen. We studied 198 out of 426 patients with clinically and/or radiologically suspect breast lesions. We found correspondence between the histological examination of the whole of the excised specimen and that of the CB in 94.9% of the cases of infiltrating carcinoma and in 71.4% of those involving ductal carcinomas in situ. The predictive value of CB was 98.9%, sensitivity was 96.1% and specificity 93.3%. These results confirmed that CB is an extremely reliable diagnostic tool in the definition of breast lesions

Effects of the number of removed lymph nodes on survival outcome in patients with sentinel node-negative breast cancer

Background: Sentinel lymph node biopsy is the gold standard surgical technique for axillary staging in patients with clinically node-negative. However, it is still uncertain what is the optimal number of sentinel lymph nodes (SLNs) to be removed to reduce the false-negative rate. The aim of this study was to investigate whether patients with a single negative SLN have a worse prognosis than those with two or more negative SLNs. Methods: A retrospective review was conducted on a large series of SLN-negative breast cancer patients. Survival outcomes and regional recurrence rate were evaluated according to the number of removed SLNs. Secondly, the contribution of different adjuvant therapies on disease-free survival was explored. Statistical analysis included the chi-square, Wilcoxon–Mann–Whitney test, and Kaplan–Meier survival analysis. Results: A total of 1080 patients were included in the study. A first group consisted of 328 patients in whom a single SLN was retrieved, and a second group consisted of 752 patients in whom two or more SLNs were retrieved. There was no relevant difference in median DFS (64.9 vs 41.4) for SLN = 1 vs SLN > 1 groups (HR 0.76, CI 95% 0.39–1.46; p = 0.38). A statistically significant difference in mDFS was showed only for HT-treated patients who were SLN = 1 if compared to SLN > 1 (100.6 months versus 35.3 months). Conclusions: There is likely a relationship between the number of resected SNL and mDFS. Our results, however, showed no relevant difference in median DFS for SLN = 1 vs SLN > 1 group, except for a subset of the patients treated with hormone therapy

Potential Activity of Albino Grifola frondosa Mushroom Extract against Biofilm of Meticillin-Resistant Staphylococcus aureus

Mushroom extracts are a rich source of natural compounds with antimicrobial properties, which are able to prevent, to some extent, the growth of foodborne pathogens. The aim of this study was to investigate the potential of extracts from albino Grifola frondosa (GF), commonly known as maitake, to inhibit the growth of some bacteria and the biofilm production by Staphylococcus aureus. We obtained not only a significant reduction of OD score between biofilm and biofilm plus albino G. frondosa extract group, but also a reduction of category of biofilm. In addition, we observed a significant presence of isolates with strong category for the biofilm group and a significant presence of isolates with absent category for the biofilm plus albino G. frondosa extract group. These results confirm that the use of albino G. frondosa extract reduces in significant way the presence of biofilm. Our results suggest and confirm that albino G. frondosa extracts could be employed as functional food and could be used as a natural additive for food process control and food safety

Distinctive features of tumor-infiltrating gd T lymphocytes in human colorectal cancer

gd T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating gd T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of gd T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5-90%) and 4%gd T cells on average, with the majority expressing Vd1. Most Vd1 and Vd2 T cells showed a predominant effector memory phenotype and had reduced production of IFN-g which was likely due to yet unidentified inhibitory molecules present in cancer stem cell secretome. Transcriptome analyses revealed that patients containing abundant gd T cells had significantly longer 5-year disease free survival rate, suggesting their efficacy in controlling tumor at very early stage

Well-being among Italian medical oncologists: An exploratory study

none12noBackground: Recently, attention has been focused on physicians' stress and quality-of-life improvement. Due to their relationship with patients, oncologists in particular are overloaded physically, emotionally and psychologically. Previous studies showed that training of communication skills improves the satisfaction and well-being of physicians and patients. Aims: Our research investigates the relationship between work stress and engagement and personal well-being in physicians working in Italian hospitals. Materials and Methods: 176 physicians were included. Doctors filled out self-report questionnaires to evaluate work stress and coping strategies, personal well-being, work engagement and two purpose-built scales to measure the degree of perceived organizational support and the level of specific training of social and relational skills. Descriptive statistics were used to analyze data, as well as correlation analysis (Pearson's r), hierarchical regression analysis (enter step) and analysis of variance (one-way ANOVA). Result: Positive and significant correlations were found between variables. Moreover, physicians who obtained higher levels of specific training on social and relational skills reported lower levels of stress. Oncologists experienced greater stress than other physicians in terms of maladaptive coping and lack of additional training. Conclusions: The study suggests that physicians' well-being is mediated by professional aspects, such as social skills in relationships with patients. © 2014 S. Karger AG, Basel.openRusso A.; De Luca R.; Cicero G.; Civilleri A.; Bronte G.; Dispenza J.; Vieni S.; Guarneri R.; Cascio V.L.; Guadagna F.P.; Foddai E.; Pace F.Russo, A.; De Luca, R.; Cicero, G.; Civilleri, A.; Bronte, G.; Dispenza, J.; Vieni, S.; Guarneri, R.; Cascio, V. L.; Guadagna, F. P.; Foddai, E.; Pace, F

Dietary restriction: could it be considered as speed bump on tumor progression road?

Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long- and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models. However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes

IL4 primes the dynamics of breast cancer progression via DUSP4 inhibition

The tumor microenvironment supplies proinflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL4 secreted by adipose tissue and estrogen receptor-positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL4 signaling with the IL4R\uce\ub1 antagonist IL4DM compromised breast cancer cell proliferation, invasion, and tumor growth by downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24-cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4by inhibiting NF-\uce\ubaB. Enforced expression of DUSP4 drove conversion of metastatic cells to nonmetastatic cells. Mechanistically, RNAi-mediated attenuation of DUSP4activated the ERKand p38 MAPK pathways, increased stem-like properties, and spawned metastatic capacity. Targeting IL4 signaling sensitized breast cancer cells to anticancer therapy and strengthened immune responses by enhancing the number of IFN\uce\ub3-positive CTLs. Our results showed the role of IL4 in promoting breast cancer aggressiveness and how its targeting may improve the efficacy of current therapies