48 research outputs found

    The role of hypoxia and SRC tyrosine kinase in glioblastoma invasiveness and radioresistance

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    CERVOXY COLLInternational audienceAdvances in functional imaging are supporting neurosurgery and radiotherapy for glioblastoma, which still remains the most aggressive brain tumor with poor prognosis. The typical infiltration pattern of glioblastoma, which impedes a complete surgical resection, is coupled with a high rate of invasiveness and radioresistance, thus further limiting efficient therapy, leading to inevitable and fatal recurrences. Hypoxia is of crucial importance in gliomagenesis and, besides reducing radiotherapy efficacy, also induces cellular and molecular mediators that foster proliferation and invasion. In this review, we aimed at analyzing the biological mechanism of glioblastoma invasiveness and radioresistance in hypoxic niches of glioblastoma. We also discussed the link between hypoxia and radiation-induced radioresistance with activation of SRC proto-oncogene non-receptor tyrosine kinase, prospecting potential strategies to overcome the current limitation in glioblastoma treatment

    Germ Cell Neoplasia in situ (GCNIS) in Testis-Sparing Surgery (TSS) for Small Testicular Masses (STMs)

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    Purpose: The testis-sparing surgery (TSS) is surgical technique accepted for small testicular masses (STMs). Frozen section examination (FSE) is an essential assessment at the time of TSS. The aim of this study is to measure the maximum distance of the foci of ITGCN from STMs.Methods: In our hospital between June 2010 and October 2017 a total of 68 patients with STM underwent a TSS. All the testis specimens were totally embedded and processed via the whole-mount method and a diagnosis of germ cell tumor with GCNIS were made. The distance between STMs and GCNIS were calculated by two pathologists directly on the slides considering for the third dimension the number of the paraffin blocks in which the foci of GCNIS were found.Results: The STMs were classic seminoma in 62 out 68 cases, embryonal carcinoma in 4 cases, while in 2 case a diagnose of mixed germ cell tumor were made. The size of the STMs was between 0.5 and 2 cm and the foci of GCNIS were observed in seminiferous tubules very closed to SMTs or as skip lesions in the surrounding testicular parenchyma, dispersed in normal testis. In 48 out of 68 cases (70.5%) foci of GCNIS were at the distance from SMTS of 1.5 cm or below and in 60 out of 68 cases (88%) at the distance of 2 cmor below The distance of GCNIS from the STMs was not related to the histological subtype of the germ cell tumor, while there is a linear correlation between size of the STMs and the distance of foci of GCNIS (p = 0.0105; r = 0.9167).Conclusion: Our data showed that foci of ITGCN were not observed beyond 2.5 cm from the STM. In particular we demonstrated that exist a linear correlation between size of STMs and distance of the foci of GCNIS from STMs (p = 0.0105; r = 0.9167). In conclusion mapping the tissue around the tumor not randomly but in targeted areas could reduce the false negative biopsies of the testis with GCNIS, increasing the radicality of the TSS procedure

    A Survey on the Knowledge and Attitudes of Italian Medical Students toward Body Donation: Ethical and Scientific Considerations

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    Post mortem body donation (PMBD) for medical training and research plays a key role in medical-surgical education. The aim of this study is to evaluate Italian medical students’ awareness and attitudes regarding this practice. A questionnaire was sent to 1781 Italian medical students (MS). A total of 472 MS responded: 406 (92.91%) had a strongly positive attitude to PMBD, while 31 (7.09%) were not in favor. The majority of subjects were Catholic (56.36%), while 185 and 21 subjects, said that they did not hold any religious beliefs, or were of other religions, respectively. Multivariate analysis showed significant associations (p-values < 0.05) between PMBD and religion, as well as perceptions of PMBD as an act of altruism, a tool for learning surgical practices, body mutilation, and an act contrary to faith. Although Italian MS believed cadaver dissection to be an important part of their education, they did not know much about it and had not received training on this altruistic choice. As future doctors, MS can play an important role in raising public awareness of the importance of PMBD for medical education and research. Specific educational programs to improve knowledge of this topic among MS are needed

    High intensity focused ultrasound as first line salvage therapy in prostate cancer local relapse after radical prostatectomy: 4-year follow-up outcomes

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    BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and the second leading cause of cancer death in developed countries. Despite the primary treatments, 20-30% of patients experience a recurrence. The main objective of this study was to evaluate the clinical efficacy of salvage high intensity focused ultrasound (HIF U) after radical prostatectomy in terms of biochemical free survival rate (BFSR) and PSA nadir. METHODS: Twenty two patients with local recurrence of Pca after radical prostatectomy underwent HIFU as first-line salvage therapy. Considering that in all HIFU experiences, PSA nadir and PSA failure are different and PSA definition of BFSR is unknown, we defined treatment success as a PSA nadir ≤0.4 ng/mL 3 months after treatment. All early and late medical and surgical complications were recorded. RESULTS: Ten of the 22 patients (45.5%) were classified as "success" three months after HIFU, showing a nadir PSA≤0.4 ng/mL; 12/22 patients (54.5%) were classified as "failure" during follow-up (median follow-up: 48 months). Seventeen of 22 (77%) patients were continent (no-pad) before HIFU. A new diagnosis of stress urinary incontinence was made in 5 cases (early onset) after treatment. A case of vesicoureteral anastomotic stenosis was treated, endoscopically through cold urethrotomy. We did not observe cases of recto-urinary fistula or persistent lower urinary tract symptoms. Two sevenths of the patients complained about de novo erectile dysfunction after HIFU. CONCLUSIONS: The positive oncologic outcomes in the short term anyway obtained in selected patients, associated with documented mild side effects, represent the basis to start more organic, prospective, randomized and multicenter study protocols, that with a long term follow-up could confirm these promising preliminary results

    The Genetic Sonogram Today: What is the Role of “Soft Markers” in the Prediction of Down Syndrome?

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    Background: The aim of this study is to evaluate the role of “soft markers” in the prediction of Down syndrome (DS). Methods: This study includes an unselected population of 1999 pregnant women who requested a fetal karyotype test using amniocentesis at gestational ages ranging from 15 to 20 weeks. Before performing the amniocentesis, an ultrasound examination was conducted to detect the presence of a series of fetal “soft markers.” Results: We identified 148 fetuses affected by DS and 1795 euploid fetuses (control group). The marker found to have the most significant likelihoodratio (LR) was increased nuchal fold. The marker found to have the greatest sensitivity was echogenic intracardiac focus. The other soft markers (as single markers) were not significant. Conclusions: An ultrasound scan cannot diagnose or rule out DS. However, it can be a useful method for modifying the baseline “a priori” probability of DS in any particular patient

    Hifu as first line salvage therapy in prostate cancer local relapse after radical prostatectomy: 4-year follow-up outcomes

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    BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and the second leading cause of cancer death in developed countries. Despite the primary treatments, 20-30% of patients experience a recurrence. The main objective of this study was to evaluate the clinical efficacy of salvage HIFU after radical prostatectomy in terms of biochemical free survival rate (BFSR) and PSA nadir. METHODS: Twenty two patients with local recurrence of Pca after radical prostatectomy underwent HIFU as first-line salvage therapy. Considering that In all HIFU experience, PSA nadir and PSA failure are different and PSA definition of BFSR is unknown, we defined Treatment success as a PSA nadir 64 0.4 ng/ml 3 months after treatment. All early and late medical and surgical complications were recorded. RESULTS: Ten of the 22 patients (45.5%) were classified as "success" three months after HIFU, showing a nadir PSA 64 0.4 ng / ml; 12/22 patients (54.5%) were classified as "failure" during follow-up (median follow-up: 48 months). Seventeen of 22 (77%) patients were continent (no-pad) before HIFU. A new diagnosis of stress urinary incontinence was made in 5 cases (early onset) after treatment. A case of vesicoureteral anastomotic stenosis was treated, endoscopically through cold urethrotomy. We didn't observe cases of recto-urinary fistula or persistent lower urinary tract symptoms. 2/7 patients, complained about de novo erectile dysfunction After HIFU. CONCLUSIONS: The positive oncologic outcomes in the short term anyway obtained in selected patients, associated with documented mild side effects, represent the basis to start more organic, prospective, randomized and multicenter study protocols, that with a long term follow-up could confirm these promising preliminary results

    Male sexual dysfunction in patients with chronic end-stage renal insufficiency and in renal transplant recipients

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    The study was conducted from December 2011 to December 2012 on 95 patients between the ages of 20 and 65 years: 44 of which had been undergoing dialysis for over a year and 51 of whom had undergone kidney transplants more than 6 months before. Comorbidities were carefully recorded, erectile function was evaluated the with IIEF5 questionnaire and serum levels of total testosterone / free and prolactin were tested at early morning (7 AM). To assess the relationship between erectile dysfunction (ED) and clinical laboratory tests, Student's t-test statistical (quantitative variables), chi-square (qualitative variables), the uni and multivariate analysis were used

    Pituitary-tumour-transforming-gene 1 expression in testicular cancer

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    Genomic instability is a feature of germ cell tumours. The pituitary-tumour-transforming-gene 1 (PTTG1) is the major effector of chromosome segregation during mitosis, protecting the cell from aneuploidy. The protein expression of this gene has been evaluated in testicular tumours by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens of testicular tissues from 83 patients undergoing therapeutic orchidectomy for seminomas (n = 53), embryonal carcinoma (n = 10), yolk sac tumour (n = 10) and teratoma (n = 10) were examined. Seminoma was associated with in situ carcinoma (CIS) in 23 samples. PTTG1 immunostaining was performed using rabbit anti-PTTG1 as a primary antibody. In CIS, only isolated cells showed nuclear staining for PTTG1. In the peripheral area of seminoma, PTTG1 was mostly detected as localised in the nucleus; in the central area of seminoma, PTTG1 staining was more intense in cytoplasm. PTTG1-positive cells were also present in the areas of seminoma infiltration. On the other hand, in embryonal carcinoma, cells had a diffuse positive immunostaining, mainly cytoplasmatic, while we did not observe an expression of PTTG1 in yolk sac tumour and mature teratoma. We firstly identified the PTTG1 expression pattern in normal testis, CIS and testicular cancer. Further investigation is needed to clarify the functional activity of PTTG1 in testicular oncogenesi

    Injectable in situ forming hydrogels based on natural and synthetic polymers for potential application in cartilage repair

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    In this work we prepared two new hyaluronic acid (HA) based in situ forming hydrogels for the potential treatment of articular cartilage damages. In particular the amino derivative of HA (HA-EDA) and its graft copolymer with α-elastin (HA-EDA-g-α-elastin) were crosslinked, in mild physiological conditions via Michael-type addition, with α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) derivatized with divinylsulfone (DV). The swelling and degradation profile of the obtained hydrogels as well as the metabolic activity of incorporated bovine articular chondrocytes were investigated. Histological analysis and scanning electron microscopy (SEM) were performed to analyze the morphology of cells after scheduled times of incubation. Moreover the influence of the α-elastin on the elastic modulus of cell free and cell containing hydrogels has been studied through atomic force microscopy (AFM). This journal i

    IN SITU FORMING HYDROGELS OF HYALURONIC ACID AND INULIN DERIVATIVES FOR CARTILAGE REGENERATION

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    An in situ forming hydrogel obtained by crosslinking of amino functionalized hyaluronic acid derivativeswith divinylsulfone functionalized inulin (INU-DV) has been here designed and characterized. In par-ticular two hyaluronic acid derivatives bearing respectively a pendant ethylenediamino (EDA) portion(HA-EDA) and both EDA and octadecyl pendant groups (HA-EDA-C18) were crosslinked through an azo-Michael reaction with INU-DV. Gelation time and consumption of DV portions have been evaluated onhydrogel obtained using HA-EDA and HA-EDA-C18derivatives with a concentration of 3% w/v and a ratio80/20 w/w respect to the crosslinker INU-DV. The presence of pendant C18chains improves mechanicalperformances of hydrogels and decreases the susceptibility to hyaluronidase hydrolysis. Bovine chon-drocytes, encapsulated during crosslinking, sufficiently survive and efficiently proliferate until 28 daysof analysis
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