Breast cancer is the most common cancer among women worldwide. Molecular and clinical evidence indicated that Fragile X Messenger Ribonucleoprotein 1 (FMRP) plays a role in different types of cancer, ...including breast cancer. FMRP is an RNA binding protein that regulates the metabolism of a large group of mRNAs coding for proteins involved in both neural processes and in epithelial-mesenchymal transition, a pivotal mechanism that in cancer is associated to tumor progression, aggressiveness and chemoresistance. Here, we carried out a retrospective case-control study of 127 patients, to study the expression of FMRP and its correlation with metastasis formation in breast cancer. Consistent with previous findings, we found that FMRP levels are high in tumor tissue. Two categories have been analyzed, tumor with no metastases (referred as control tumors, 84 patients) and tumor with distant metastatic repetition, (referred as cases, 43 patients), with a follow-up of 7 years (mean). We found that FMRP levels were lower in both the nuclei and the cytoplasm in the cases compared to control tumors. Next, within the category cases (tumor with metastases) we evaluated FMRP expression in the specific sites of metastasis revealing a nuclear staining of FMRP. In addition, FMRP expression in both the nuclear and cytoplasmic compartment was significantly lower in patients who developed brain and bone metastases and higher in hepatic and pulmonary sites. While further studies are required to explore the underlying molecular mechanisms of FMRP expression and direct or inverse correlation with the secondary metastatic site, our findings suggest that FMRP levels might be considered a prognostic factor for site-specific metastasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the safety and clinical efficacy of AA-PRP injections for pattern hair loss. AA-PRP, prepared from a small volume of blood, was injected on half of the selected patients’ scalps with ...pattern hair loss. The other half was treated with placebo. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair re-growth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki-67 evaluation. At the end of the 3 cycles of treatment, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 18.0 hairs in the target area, and a mean increase in total hair density of 27.7 ( number of hairs/cm2) compared with baseline values. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles two weeks after the last AA-PRP treatment compared to baseline value (P<0.05). We also observed an increase of Ki67+ keratinocytes of epidermis and of hair follicular bulge cells and a slight increase of small blood vessels around hair follicles in the treated skin compared to baseline (P<0.05).
Platelet rich plasma (PRP) and Micrografts containing human follicle mesenchymal stem cells (HF-MSCs) were tried as a potential treatment for androgenetic alopecia (AGA). However, little to no work ...has yet to be seen wherein the bio-molecular pathway of HF-MSCs or PRP treatments were analyzed. The aims of this work are to report the clinical effectiveness of HF-MSCs and platelet-rich plasma evaluating and reviewing the most updated information related to the bio-molecular pathway. Twenty-one patients were treated with HF-MSCs injections and 57 patients were treated with A-PRP. The Wnt pathway and Platelet derived-growth factors effects were analyzed. 23 weeks after the last treatment with mean hair thickness increments (29 ± 5.0%) over baseline values for the targeted area. 12 weeks after the last injection with A-PRP mean hair count and hair density (31 ± 2%) increases significantly over baseline values. The increment of Wnt signaling in Dermal Papilla Cells evidently is one of the principal factors that enhances hair growth. Signaling from mesenchymal stem cells and platelet derived growth factors positively influences hair growth through cellular proliferation to prolong the anagen phase (FGF-7), inducing cell growth (ERK activation), stimulating hair follicle development (β-catenin), and suppressing apoptotic cues (Bcl-2 release and Akt activation).
The potential plasticity and therapeutic utility in tissue regeneration of human adipose‐derived stem cells (ASCs) isolated from adult adipose tissue have recently been highlighted. The use of ...autologous platelet‐rich plasma (PRP) represents an alternative strategy in regenerative medicine for the local release of multiple endogenous growth factors. Here we investigated the signaling pathways and effects of PRP and human recombinant insulin on proliferation and adipogenic differentiation of ASCs in vitro. PRP stimulated proliferation (EC50 = 15.3 ± 1.3% vol/vol), whereas insulin's effect was the opposite (IC50 = 3.0 ± 0.5 μM). Although PRP alone did not increase adipogenesis, in association with insulin it prevented ASC proliferative arrest, greatly enhanced intracytoplasmic lipid accumulation, strongly increased serine/threonine kinase Akt phosphorylation and mouse monoclonal anti‐sterol regulatory element binding protein‐1 accumulation, and downregulated Erk‐1 activity; adipogenic effects were markedly prevented by the Akt inhibitor wortmannin. PRP with insulin synergistically upregulated fibroblast growth factor receptor (FGFR) and downregulated epidermal growth factor receptor (ErbB) expression; moreover, PRP in association prevented insulin‐induced insulin‐like growth factor‐1 receptor and insulin receptor downregulation. The inhibition of FGFR‐1, epidermal growth factor receptor (EGFR), and epidermal growth factor receptor‐2 (ErbB2) activity reduced ASC proliferation, but only that of FGFR‐1 reduced adipogenesis and Akt phosphorylation, whereas the ErbB2 inhibition effects were the opposite. However, EGFR activity was needed for ErbB2‐mediated inhibition of ASC adipogenesis. Clinically, the injection of insulin further ameliorated patients' 1‐year PRP‐induced fat graft volume maintenance and contour restoring. Our results ascertain that PRP in association with insulin greatly potentiates adipogenesis in human ASCs through a FGFR‐1 and ErbB2‐regulated Akt mechanism. The ameliorated clinical fat graft maintenance suggests additional useful translational applications of combined PRP‐insulin treatment in regenerative medicine.
Context: Breast lipofilling usually involves three different stages (harvesting, processing, and placement), and in each of these phases, adipocyte cells can be damaged. Our technique of fat ...placement is quite different from the others as we focus our attention on the last stage of fat graft procedure, which could explain the better results in graft survival. Aims: Our method is focused on eliminating any unnecessary manipulation of the graft so as to optimize graft retention and clinical outcomes: Controlled movement and slow rate of fat injection are the cornerstone of our technique and guarantee a nontraumatic fat transfer and a greater survival rate of adipocytes. Settings and Design: This was a retrospective cohort study. Materials and Methods: Of 120 patients (average age 41,5 years) affected by breast soft tissue defects, 60 were managed with the lipofilling procedure using fat graft injected by "Gentle technique." To establish the effects of the injection's procedure, we compared the results obtained in fat graft maintenance with a control group made up of 60 patients, treated with fat graft injection according to Coleman procedure. Statistical Analysis Used: Values are expressed as mean plus standard error and analyzed using Student's t test. Results: In patients treated with Gentle technique, we observed a 60.5% + 12.5% maintenance of contour restoring and three-dimensional volume after 1 year (P < 0.0001 vs. control group); we compared the results obtained with only 39% + 4.4% of the control group treated with fat graft injected according to Coleman. Conclusions: Controlled 26 movement and slow rate of fat injection are the cornerstone of our technique and guarantee a nontraumatic fat transfer and a greater 27 survival rate of adipocytes.
The authors report their experience about the use of P.R.L. PLATELET RICH LIPOTRANSFERT method (platelet rich plasma mixed fat grafting) in 223 patients affected by soft tissue defects (ulcers, ...Romberg syndrome, Hemifacial atrophy, loss of substance, and signs of aging). This paper introduces the reader to PRP therapy and reviews the current literature on this emerging treatment modality, showing at the current clinical use of PRP in plastic and reconstructive surgery, with description of innovative methods and future prospects. This technique provides a promising alternative to surgery by promoting safe and natural healing. Here recent studies concerning the use of PRP in the treatment of chronic ulcers and soft tissue defect are reviewed.
This paper presents the measurements on first very thin Ultra-Fast Silicon Detectors (UFSDs) produced by Fondazione Bruno Kessler; the data have been collected in a beam test setup at the CERN PS, ...using beam with a momentum of 12 GeV/c. UFSDs with a nominal thickness of 25 and 35
μ
m and an area of 1
×
1
mm
2
have been considered, together with an additional HPK 50-
μ
m thick sensor, taken as reference. Their timing performances have been studied as a function of the applied voltage and gain. A time resolution of about 25 ps and of 22 ps at a voltage of 120 and 240 V has been obtained for the 25 and 35
μ
m thick UFSDs, respectively.
This paper describes the new concept of the double LGAD (low-gain avalanche diodes). The goal was to increase the charge at the input of the electronics, keeping a time resolution equal to or better ...than a standard (single) LGAD; this has been realized by adding the charges of two coupled LGADs while still using a single front-end electronics. The study here reported has been done starting from single LGAD with a thickness of 25 µm, 35 µm and 50 µm.
Various experiments are searching for detectors that can cover large areas (as in the present LHC experiments) with excellent timing performances and insensitivity to magnetic field. A detector based ...on scintillators coupled to SiPM can fulfil these requirements. SiPMs are indeed replacing the standard PhotoMultiplier technology thanks to the many advantages, with the corresponding possibility to achieve also higher segmentations in calorimetry or other applications. Also in view of future colliders experiments like HL-LHC or FCC or medical applications like TOF-PET, an important R&D on timing performances of SiPMs-scintillator detectors has begun, with the goal of including them in the list of possible 4-D tracking-timing devices.
An R&D on SiPM coupled to scintillator time resolution has been performed in a cosmic ray setup. Different kind of SiPMs, geometries of SiPMs coupled to the scintillator and different size of scintillator have been also studied. A time resolution of ∼69 ps, comprehensive of the full electronic chain, from the front-end to the readout electronics, has been achieved with SiPMs coupled to a 2x2x3 cm3 plastic scintillator.
Abstract
The direct response of Silicon PhotoMultipliers being
traversed by a MIP charged particle have been studied in a
systematic way for the first time. Using beam test data, time
resolution and ...the crosstalk probability have been measured. A
characterization of the SiPM by means of a laser beam is also
reported. The results obtained for different sensors indicate a
measured time resolution around 40–70 ps. Although particles are
expected to traverse only one SPAD per event, crosstalk measurements
on different sensors indicate an unexpected higher value with
respect to the one related to the sensor noise.
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