10 research outputs found
The prognostic value of H3 K27me3 in meningiomas: A review on current evidence and methodological challenges
No full text: Meningiomas are the most common primary intracranial neoplasms. Although they mostly exhibit a benign course, some cases recur after surgery and show high morbidity and mortality rates. In addition to currently established prognostic factors, such as the extent of surgical resection and tumor grade assessed according to World Health Organization (WHO) criteria, the prognostic significance of the immunohistochemical loss of Histone 3 trimethylation in Lysine 27 (H3 K27me3) has emerged in meningiomas. This review examined original studies that analyzed the immunohistochemical expression of H3 K27me3 in meningiomas and its correlation with various features, including overall survival (OS), recurrence-free survival (RFS), and WHO grade. A literature search was conducted in PubMed for English-language publications up to July 8, 2024. Sixteen studies were included in this review. In summary, current evidence indicates that H3 K27me3 loss is more frequent in tumors exhibiting higher biological aggressiveness, as reflected by a significant association with a higher WHO grade, proliferative index, and prognostically unfavorable methylation classes. In addition, published studies consistently indicate a negative prognostic significance for progression-recurrence-free survival (PFS/RFS) in WHO grade 2 meningiomas and OS in WHO grade 3 tumors. However, the lack of a standardized definition for H3 K27me3 loss significantly hampers the incorporation of the H3 K27me3 immunohistochemical assay into routine practice to establish the prognosis of meningiomas
Statin-Sensitive Akt1/Src/Caveolin-1 Signaling Enhances Oxidative Stress Resistance in Rhabdomyosarcoma
No full textObjective: The aim of the present study was to investigate the effects of targeting the mevalonate pathway (MVP) in rhabdomyosarcoma (RMS), a soft tissue tumor with a prevalence in young people. Methods: In silico analyses of RNA datasets were performed to correlate MVP with RMS patient survival. The sensitivity of RMS cell lines to MVP inhibitors was assessed in vitro by analysis of cell growth (crystal violet and clonogenic assays), cell migration (wound healing assay), cell survival (neutral red assay), and oxidative stress (ROS assay). The effects of MVP inhibitors were tested in vivo by analyzing RMS xenografts grown in NOD/SCID mice. Quantification of protein targets was performed using immunoblotting or immunohistochemistry analyses. Results: By analyzing RNA datasets from rhabdomyosarcoma (RMS), a soft tissue tumor with a prevalence in young people, we found In silico analysis showed upregulation of sterol regulatory element-binding protein 2 (SREBP2) and mevalonate pathway (MVP) genes, including 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), farnesyl-diphosphate synthase (FDPS), squalene epoxidase (SQLE), which correlated with worse overall patient survival and predicted statin sensitivity. Targeting of MVP in human RD and RH30 lines by inhibitors of SREBP2 (fatostatin), HMGCR (lovastatin and simvastatin), and FDPS (zoledronic acid) resulted in In impaired cell growth, migration, and viability, and increased oxidative cell death in combination with actinomycin D. Conversely, cholesterol (CHO) supplementation enhanced cell growth and migration. human RD and RH30 lines, treatment with 0.01–1 μM doses of fatostatin (SREBP2 inhibitor), lovastatin and simvastatin (HMGCR inhibitors), and zoledronic acid (FDPS inhibitor) impaired cell growth and migration, which were conversely stimulated by 50–100 μM cholesterol (CHO) supplementation. Treatment of RMS lines with higher doses of SREBP2 and MVP inhibitors (5–50 μM) promoted oxidative cell death and chemosensitization in combination with actinomycin D. Administration of lFatostatin and lovastatin or fatostatin to RD and RH30 cells produced produced a rapid attenuation of Erk1/2 and Akt1 phosphorylation signaling in RMS lines, and oral administration of lovastatin reduced tumor mass detectable after 4 h of treatment. Furthermore, tumor mass growth of xenografted RD cells in NOD/SCID mice was reduced by oral administration of lovastatin. LastlyFinally, we found we found that the forced Akt1 activation in RD cells was sufficient to drive SREBP2, HMGCR and SQLE protein expression, and enhance cell death promoting increased susceptibility to MVP inhibitors. Conclusions: Taken together, these data suggest that the axis formed by Akt1, SREBP2 and MVP axis is critical for RMS tumor growth, migration, and oxidative stress protection mainly primarily through the maintenancemaintaining adequate CHO levels that enable of proper intracellular signaling CHO levels that ensure proper intracellular signaling. Therefore, targeting stimulating CHO levels depletion by via SREBP2 and MVP inhibition may represent a viable option to improve the combination therapy protocol, especially in pAkt1-positive RMS
Lactotroph PitNET/adenoma associated to granulomatous hypophysitis in a patient with Crohn's disease: A case report
No full textGranulomatous hypophysitis is a rare and poorly understood condition. Although certain cases are treated as primary pituitary autoimmune disorders, rare cases may be associated with pituitary neuroendocrine tumours (PitNETs) and systemic inflammatory diseases. Here, we report a case of a 47-year-old man that underwent endoscopic trans-sphenoidal excision of a pituitary mass diagnosed as PitNET. On histologic evaluation, the neoplasm showed an admixture of granulomas with extensive inflammatory infiltrate and lactotroph PitNET/adenoma. Careful anamnestic examination revealed a diagnosis of Crohn's disease 20 years prior. Although rarely done, both PitNET and Crohn's disease may be associated with granulomatous hypophysitis, and our patient had both conditions. During the 6-year follow-up, PitNETs and hypophysitis did not recur, while Crohn's disease was only partially controlled by medical therapy. To our knowledge, this is the first description of association of granulomatous hypophysitis, PitNET and Crohn's disease
Correction to: Histone deacetylase inhibitor ITF2357 (givinostat) reverts transformed phenotype and counteracts stemness in in vitro and in vivo models of human glioblastoma (Journal of Cancer Research and Clinical Oncology, (2019), 145, 2, (393-409), 10.1007/s00432-018-2800-8)
No full textIn the original publication, the 6th author’s first name and the last name was inverted and incorrectly published. The correct author name is Letizia Ferella
3D Printing for Customized Bone Reconstruction in Spheno-Orbital Meningiomas: A Systematic Literature Review and Institutional Experience
No full textBackground: The treatment of spheno-orbital meningiomas (SOMs) requires extensive bone resections, creating significant defects in a complex geometrical space. Bone reconstruction represents a fundamental step that optimizes long-term aesthetic and functional outcomes. In recent years, 3D printing technology has also been exploited for complex skull base reconstructions, but reports remain scarce. Methods: We retrospectively analyzed four consecutive patients who underwent SOM resection and one-step 3D PEEK customized reconstruction from 2019 to 2023. A systematic review of 3D printing customized implants for SOM was then performed. Results: All patients underwent a frontotemporal craniotomy, removal of SOM, and reconstruction of the superolateral orbital wall and pterional region. The aesthetic outcome was extremely satisfactory in all cases. No orbital implant malposition or infectious complications were documented. Eleven papers were included in the literature review, describing 27 patients. Most (23) patients underwent a single-stage reconstruction; in three cases, the implant was positioned to correct postoperative delayed enophthalmos. Porous titanium was the most used material (16 patients), while PEEK was used in three cases. Prosthesis malposition was described in two (7.4%) patients. Conclusions: Single-step reconstruction with a personalized 3D PEEK prosthesis represents a valid reconstruction technique for the treatment of SOMs with good aesthetic outcomes
Synthetic inhibition of SREBP2 and the mevalonate pathway blocks rhabdomyosarcoma tumor growth in vitro and in vivo and promotes chemosensitization
No full textObjective: The aim of the present study was to investigate the effects of targeting the mevalonate pathway (MVP) in rhabdomyosarcoma (RMS), a soft tissue tumor with a prevalence in young people. Methods: In silico analyses of RNA datasets were performed to correlate MVP with RMS patient survival. The sensitivity of RMS cell lines to MVP inhibitors was assessed in vitro by analysis of cell growth (crystal violet and clonogenic assays), cell migration (wound healing assay), cell survival (neutral red assay), and oxidative stress (ROS assay). The effects of MVP inhibitors were tested in vivo by analyzing RMS xenografts grown in NOD/SCID mice. Quantification of protein targets was performed using immunoblotting or immunohistochemistry analyses. Results: In silico analysis showed upregulation of sterol regulatory element-binding protein 2 (SREBP2) and MVP genes, including 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), farnesyl-diphosphate synthase (FDPS), squalene epoxidase (SQLE), which correlated with worse overall patient survival. Targeting of MVP in human RD and RH30 lines by inhibitors of SREBP2 (fatostatin), HMGCR (lovastatin and simvastatin), and FDPS (zoledronic acid) resulted in impaired cell growth, migration, and viability, and increased oxidative cell death in combination with actinomycin D. Conversely, cholesterol (CHO) supplementation enhanced cell growth and migration. Fatostatin and lovastatin produced rapid attenuation of Erk1/2 and Akt1 signaling in RMS lines, and oral administration of lovastatin reduced tumor mass growth of xenografted RD cells in NOD/SCID mice. Finally, we found that forced Akt1 activation in RD cells was sufficient to drive SREBP2, HMGCR and SQLE protein expression, promoting increased susceptibility to MVP inhibitors. Conclusions: These data suggest that the Akt1, SREBP2 and MVP axis is critical for RMS tumor growth, migration, and oxidative stress protection primarily through maintaining adequate CHO levels that enable proper intracellular signaling. Therefore, stimulating CHO depletion via SREBP2 and MVP inhibition may represent a viable option to improve the combination therapy protocol, especially in pAkt1-positive RMS
3D Printing for Customized Bone Reconstruction in Spheno-Orbital Meningiomas: A Systematic Literature Review and Institutional Experience
No full textBackground: The treatment of spheno-orbital meningiomas (SOMs) requires extensive bone resections, creating significant defects in a complex geometrical space. Bone reconstruction represents a fundamental step that optimizes long-term aesthetic and functional outcomes. In recent years, 3D printing technology has also been exploited for complex skull base reconstructions, but reports remain scarce. Methods: We retrospectively analyzed four consecutive patients who underwent SOM resection and one-step 3D PEEK customized reconstruction from 2019 to 2023. A systematic review of 3D printing customized implants for SOM was then performed. Results: All patients underwent a frontotemporal craniotomy, removal of SOM, and reconstruction of the superolateral orbital wall and pterional region. The aesthetic outcome was extremely satisfactory in all cases. No orbital implant malposition or infectious complications were documented. Eleven papers were included in the literature review, describing 27 patients. Most (23) patients underwent a single-stage reconstruction; in three cases, the implant was positioned to correct postoperative delayed enophthalmos. Porous titanium was the most used material (16 patients), while PEEK was used in three cases. Prosthesis malposition was described in two (7.4%) patients. Conclusions: Single-step reconstruction with a personalized 3D PEEK prosthesis represents a valid reconstruction technique for the treatment of SOMs with good aesthetic outcomes
A return to cinema d'impegno? Cinematic engagements with organized crime in Italy, 1950-2010
No full textThis thesis seeks to interrogate the mutual relationship between representations of
organized crime and commitment in Italian film (cinema d’impegno). Since the
Second World War, images of bandits, mafiosi and criminal rackets have been
central to some of the most important political films released, including In nome
della legge (Pietro Germi, 1949), Salvatore Giuliano (Francesco Rosi, 1961) and
A ciascuno il suo (Elio Petri, 1967). The ‘mafia film’ in Italy thus has a rich
heritage of powerfully engaged cinema that remains a far cry from its glamourized
international counterpart. Yet this ‘filone’, like cinema d’impegno widely, has
suffered from the endemic political apathy that accompanied advance of
postmodernity.
Drawing on recent scholarship on postmodern impegno, as well as on some of the
most important contemporary mafia films that have led critics to announce a
‘return’ to this heritage of engaged cinema, this thesis will interrogate the image
of organized crime today and its problematic mimicry of this past. It will employ
a historically comparative approach, beginning with an analysis of the important
waves of committed cinema in the post-War years. It then turns to the social role
of the cinema since the 1990s, when, despite the disintegration of political ‘grand
narratives’, the constant renewal of the trauma of organized crime has continued
to produce boldly political cinematic denunciations.
A secondary aim of the thesis is to bring into question the very notion of impegno.
As the discourses that are analysed in the first half show, the Marxist core of
many of the political mafia films has led to a narrow understanding of the
organized crime imagery. Building on Marxist theorists, from Lukács to Jameson,
and extending a better critical appreciation of the spectator, this discussion seeks
to bring into focus the importance of genre cinema in the dialectical creation of a
political mafia image
Aggressive PitNETs and Potential Target Therapies: A Systematic Review of Molecular and Genetic Pathways
No full textRecently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs’ aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs
ВОЗМОЖНОСТИ ПРИМЕНЕНИЯ ЛАКТОФЕРРИНА У ДЕТЕЙ ПЕРВОГО ГОДА ЖИЗНИ
No full textThe author summarizes the results of research of the antibacterial, antiviral and antifungal properties of multifunctional human protein — lactoferrin, in order to determine the prospects for its use in the prevention and treatment of infectious diseases of children in their first year of life. The mechanisms of anti-infectious effect of this protein with breastfed children have been described. Basic differences between human lactoferrin and cattle lactoferrin have been shown. Biotechnology of obtaining recombinant human lactoferrin from the milk of genetically engineered dairy animals (goat-producers) has been described. According to the studies, both by physical and chemical parameters and biological activity, human lactoferrin, obtained from milk-producing goats, corresponds to its natural counterpart.В статье обобщены результаты исследований, посвященных изучению антибактериальных, противовирусных и противогрибковых свойств многофункционального белка человека — лактоферрина, для определения перспектив его применения с целью профилактики и лечения инфекционной патологии у детей первого года жизни. Описаны механизмы противоинфекционного действия этого белка у детей, находящихся на грудном вскармливании. Показаны основные различия между лактоферрином человека и лактоферрином крупного рогатого скота. Описана биотехнология получения рекомбинантного лактоферрина человека из молока генно-инженерных молочных животных (коз-продуцентов). Согласно проведенным исследованиям, как по физико-химическим параметрам, так и по биологической активности лактоферрин человека, выделенный из молока коз-продуцентов, соответствует его природному аналогу
