Implant-Based Breast Reconstruction after Risk-Reducing Mastectomy in BRCA Mutation Carriers: A Single-Center Retrospective Study

Women with BRCA gene mutations have a higher lifetime risk of developing breast cancer. Furthermore, cancer is usually diagnosed at a younger age compared to the wild-type counterpart. Strategies for risk management include intensive surveillance or risk-reducing mastectomy. The latter provides a significant reduction of the risk of developing breast cancer, simultaneously ensuring a natural breast appearance due to the preservation of the skin envelope and the nipple-areola complex. Implant-based breast reconstruction is the most common technique after risk-reducing surgery and can be achieved with either a submuscular or a prepectoral approach, in one or multiple stages. This study analyzes the outcomes of the different reconstructive techniques through a retrospective review on 46 breasts of a consecutive, single-center case series. Data analysis was carried out with EpiInfo version 7.2. Results of this study show no significant differences in postoperative complications between two-stage tissue expander/implant reconstruction and direct-to-implant (DTI) reconstruction, with DTI having superior aesthetic outcomes, especially in the prepectoral subgroup. In our experience, the DTI prepectoral approach has proven to be a safe and less time-consuming alternative to the submuscular two-stage technique, providing a pleasant reconstructed breast and overcoming the drawbacks of subpectoral implant placement

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

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

An Overview of In Vitro Assays of 64Cu-, 68Ga-, 125I-, and 99mTc-Labelled Radiopharmaceuticals Using Radiometric Counters in the Era of Radiotheranostics

Radionuclides are unstable isotopes that mainly emit alpha (alpha), beta (beta) or gamma (gamma) radiation through radiation decay. Therefore, they are used in the biomedical field to label biomolecules or drugs for diagnostic imaging applications, such as positron emission tomography (PET) and/or single-photon emission computed tomography (SPECT). A growing field of research is the development of new radiopharmaceuticals for use in cancer treatments. Preclinical studies are the gold standard for translational research. Specifically, in vitro radiopharmaceutical studies are based on the use of radiopharmaceuticals directly on cells. To date, radiometric beta- and gamma-counters are the only tools able to assess a preclinical in vitro assay with the aim of estimating uptake, retention, and release parameters, including time- and dose-dependent cytotoxicity and kinetic parameters. This review has been designed for researchers, such as biologists and biotechnologists, who would like to approach the radiobiology field and conduct in vitro assays for cellular radioactivity evaluations using radiometric counters. To demonstrate the importance of in vitro radiopharmaceutical assays using radiometric counters with a view to radiogenomics, many studies based on Cu-64-, Ga-68-, I-125-, and Tc-99m-labeled radiopharmaceuticals have been revised and summarized in this manuscript

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

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

The role of microRNAs in driving EGFR-TKI resistance in NSCLC cell lines

Background: the inhibition of EGFR kinase activity by tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, can result in improved response and prolonged progression-free survival (PFS) in NSCLC patients harboring sensitizing exon 19del and exon 21 L858R mutations. Unfortunately, almost all patients will develop resistance to EGFR-TKI, in particular T790M is the most frequent mutation. Nowadays, new methods are urgently needed for a rapid, cost-effective and non-invasive identification of biomarkers as a valuable tool for obtaining the genetic follow-up data during the course of the disease. Circulating microRNAs might represent a new precious biomarker for patients\u2019 monitoring. The study aimed to verify the association between microRNAs expression and EGFR mutational status in adenocarcinoma wt and EGFR-TKI sensitive mutated (del19) cells. Methods: EGFR wt and mutated adenocarcinoma cells (A549, HCC827), were cultured in RPMI1640 and incubated at 37C in 5% CO2. Cell viability before treatment was evaluated by MTT assay and then cells were treated with Erlotinib at growing concentration. MicroRNAs were extracted by using miRNeasy mini kit (QIAGEN). Nucleic acids quantity and quality was evaluated through the NanoDrop ND-2100 Bioanalyzer whereas integrity through the 2100 Bioanalyzer. MicroRNAs after retrotranscription were profiled through TaqMan Array Human MicroRNA Cards v2.0. Results: microRNAs extracted from A549 (wild-type) and HCC827 (del19) were profiled and differential expression analyzed at basal conditions (no treatment) using the wt cell as control. The miRNAs analysis highlighted that among the up-regulated microRNAs (miR-7, miR-18a, miR-106b, miR-200b, miR-505, miR-625), the miR-7 expression levels were 10 times higher, whereas among the down-regulated miRNAs (let-7f, miR-10b, miR-192, miR-193, miR-194, miR-767, miR-801), let-7f was 12 times lower. This signature may represent a valid start point for studying variations of the aforementioned miRNAs levels during TKIs treatment in order to demonstrate their involvement in inducing resistance. Conclusions: to outline molecular mechanisms responsible for resistance onset as consequence of TKIs treatment, the hypotetical role of miRNAs has been studied. The preliminary data, obtained so far only in cultured cell lines at basal conditions, would acquire higher relevance, if their involvement may be confirmed also in TKI-treated cells

Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer Cells

Copyright © 2020 Murugaiah, Agostinis, Varghese, Belmonte, Vieni, Alaql, Alrokayan, Khan, Kaur, Roberts, Madan, Bulla and Kishore. Human surfactant protein D (SP-D) belongs to the family of collectins that is composed of a characteristic amino-terminal collagenous region and a carboxy-terminal C-type lectin domain. Being present at the mucosal surfaces, SP-D acts as is a potent innate immune molecule and offers protection against non-self and altered self-such as pathogens, allergens, and tumour. Here, we examined the effect of a recombinant fragment of human SP-D (rfhSP-D) on a range of breast cancer lines. Breast cancer has four molecular subtypes characterised by varied expression of oestrogen (ER), progesterone (PR) and EGF receptors (HER2). The cell viability of HER2 over-expressing (SKBR3) and triple-positive (BT474) breast cancer cell lines (but not of triple-negative cell line (BT20), was reduced following rfhSP-D treatment at 24h. Upregulation of p21/p27 cell cycle inhibitors and p53 phosphorylation (Ser15) in rfhSP-D-treated BT474 and SKBR3 cell lines signified G2/M cell cycle arrest. Cleaved caspase 9 and 3 were detected in rfhSP-D- treated BT474 and SKBR3 cells, suggesting an involvement of intrinsic apoptosis pathway. However, rfhSP-D-induced apoptosis was nullified in the presence of hyaluronic acid whose increased level in breast tumor microenvironment is associated with malignant tumor progression and invasion. rfhSP-D bound to solid-phase HA and promoted tumor cell proliferation. rfhSP-D-treated SKBR3 cells in the presence of hyaluronic acid showed decreased transcriptional levels of p53 when compared to SKBR3 cells treated with rfhSP-D only. Thus, hyaluronic acid appears to negate the anti-tumorigenic properties of rfhSP-D against HER2-over-expressing and triple-positive breast cancer cells.King Saud University, Riyadh, International Scientific Partnership Program (ISPP) ISPP-145; Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy, RC20/16 and 5MILLE15D