1,721,053 research outputs found
MYCOSIS FUNGOIDES: NOVEL THERAPEUTIC APPROACHES TARGETING THE CUTANEOUS LYMPHOCYTE ANTIGEN (CLA)
Get PDFBackground
Mycosis fungoides (MF) is the most common form of cutaneous T cell lymphoma. There are currently few effective therapies for the treatment of MF. Treatments for the early stages generally consist of a skin-directed therapy, and treatments for the late stages are generally systemic, and often combined. Although the initial stages of mycosis fungoides have a moderate clinical course, 30% of patients relapse or prove to be refractory to currently used treatments and are destined to progress to advanced stages of the disease for which, in fact, there is not a curative treatment. Therefore, the development of new therapeutic strategies is fundamental. While the Cutaneous Lymphocyte Antigen (CLA) is strongly expressed by MF tumor cells, it could be a specific molecular target for the treatment of MF.
The aim of the whole PhD project was to investigate novel therapeutic approaches targeting CLA for the treatment of MF. The first specific aim was to investigate the antitumor effect of a CLA-targeted Near‐infrared photoimmunotherapy (NIR-PIT) on MF cells and the second specific aim was to investigate the antitumor effect of an antibody-drug conjugate (ADC) consisting of an anti-CLA monoclonal antibody and monomethyl auristatin E (MMAE).
Methods
In vitro validation of anti-CLA monoclonal antibody-based approaches were performed using a MF cell line called Myla CD4+ cell line.
In vivo studies are ongoing on zebrafish embryo model of MF created by the injection of Myla CD4+ cells into the yolk sac at 2 days post fertilization.
Results
Treatment with anti-CLA monoclonal antibody alone or near infrared light irradiation alone exhibited very modest pro-death effects, while the combination of the two induced a substantial increase in death in the MF cell line showing that CLA-targeted NIR PIT has a marked anti-tumor effect in vitro.
Conversely, the anti-CLA-MMAE antibody drug conjugate exhibited in vitro lower cytotoxic activity compared to anti-CLA monoclonal antibody or MMAE alone.
In vivo validation phases studies are ongoing to investigate the efficacy of these anti-CLA monoclonal antibody-based approaches. Preliminary data are encouraging but are still under evaluation.
Discussion
An anti-CLA monoclonal antibody-based approach may represent a novel and highly selective treatment for this disease.
While CLA-targeted NIR-PIT shows a marked anti-tumor effect on MF cells in vitro, it is an attractive candidate for in vivo studies and ultimately for clinical trials.
The anti-CLA-MMAE ADC shows low cytotoxicity activity in vitro which could be explained by the lack of internalization of the ADC into the cells. However, it has recently been demonstrated that in vivo non-internalizing antibodies may have potent anti-cancer activity thanks to proteolytic release of MMAE in the subendothelial extracellular matrix. Thus, anti-CLA-MMAE ADC may be effective in vivo.
The xenotransplantation experiments performed to evaluate the proliferation of MF cells in zebrafish embryos have given very positive and extremely encouraging results, confirming the possible use of this animal species as a model for the study of this pathology.Background
Mycosis fungoides (MF) is the most common form of cutaneous T cell lymphoma. There are currently few effective therapies for the treatment of MF. Treatments for the early stages generally consist of a skin-directed therapy, and treatments for the late stages are generally systemic, and often combined. Although the initial stages of mycosis fungoides have a moderate clinical course, 30% of patients relapse or prove to be refractory to currently used treatments and are destined to progress to advanced stages of the disease for which, in fact, there is not a curative treatment. Therefore, the development of new therapeutic strategies is fundamental. While the Cutaneous Lymphocyte Antigen (CLA) is strongly expressed by MF tumor cells, it could be a specific molecular target for the treatment of MF.
The aim of the whole PhD project was to investigate novel therapeutic approaches targeting CLA for the treatment of MF. The first specific aim was to investigate the antitumor effect of a CLA-targeted Near‐infrared photoimmunotherapy (NIR-PIT) on MF cells and the second specific aim was to investigate the antitumor effect of an antibody-drug conjugate (ADC) consisting of an anti-CLA monoclonal antibody and monomethyl auristatin E (MMAE).
Methods
In vitro validation of anti-CLA monoclonal antibody-based approaches were performed using a MF cell line called Myla CD4+ cell line.
In vivo studies are ongoing on zebrafish embryo model of MF created by the injection of Myla CD4+ cells into the yolk sac at 2 days post fertilization.
Results
Treatment with anti-CLA monoclonal antibody alone or near infrared light irradiation alone exhibited very modest pro-death effects, while the combination of the two induced a substantial increase in death in the MF cell line showing that CLA-targeted NIR PIT has a marked anti-tumor effect in vitro.
Conversely, the anti-CLA-MMAE antibody drug conjugate exhibited in vitro lower cytotoxic activity compared to anti-CLA monoclonal antibody or MMAE alone.
In vivo validation phases studies are ongoing to investigate the efficacy of these anti-CLA monoclonal antibody-based approaches. Preliminary data are encouraging but are still under evaluation.
Discussion
An anti-CLA monoclonal antibody-based approach may represent a novel and highly selective treatment for this disease.
While CLA-targeted NIR-PIT shows a marked anti-tumor effect on MF cells in vitro, it is an attractive candidate for in vivo studies and ultimately for clinical trials.
The anti-CLA-MMAE ADC shows low cytotoxicity activity in vitro which could be explained by the lack of internalization of the ADC into the cells. However, it has recently been demonstrated that in vivo non-internalizing antibodies may have potent anti-cancer activity thanks to proteolytic release of MMAE in the subendothelial extracellular matrix. Thus, anti-CLA-MMAE ADC may be effective in vivo.
The xenotransplantation experiments performed to evaluate the proliferation of MF cells in zebrafish embryos have given very positive and extremely encouraging results, confirming the possible use of this animal species as a model for the study of this pathology
Invecchiamento cutaneo e tumori nell'anziano
No full textTra i segni del processo di involuzione dell’essere umano, quelli legati all’invecchiamento cutaneo sono tra i più visibili. La cute è esposta costantemente a molteplici fattori in grado di accelerarne il naturale processo di invecchiamento; è possibile riconoscere due tipi di invecchiamento:
un invecchiamento intrinseco (di natura principalmente cronologica e genetica), il quale interessa fondamentalmente le regioni che di solito non sono esposte al sole; un invecchiamento estrinseco, in rapporto con i fattori ambientali, soprattutto con l’esposizione ai raggi solari; tale invecchiamento predomina quindi a livello delle zone scoperte (“zone foto-esposte”) e interessa in particolare i soggetti con capelli e occhi chiari (fototipo basso). Questo tipo d’invecchiamento cutaneo può essere favorito da numerosi fattori, oltre che dalla foto-esposizione: fattori comportamentali (abitudini alimentari, tabacco, alcol, droghe); fattori catabolici (patologie croniche); fattori endocrini
Persistence of superficial basal cell carcinoma during pembrolizumab treatment for metastatic melanoma
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Atypical skin reaction in a patient treated with gefitinib for advanced lung cancer: A case report and review of the literature
No full textGroup-based Early Start Denver Model: An educational approach for pupils with Autism Spectrum Disorder in Italian preschools = Group-based Early Start Denver Model: un modello educativo per alunni con Disturbo dello Spettro Autistico nelle scuole dell’infanzia italiane
No full textThe article outlines the main features of the Group-based Early Start Denver Model (G-ESDM), an intervention for children with ASD that has gained prominence in recent years (Vivanti, Duncan, Dawson, Rogers, 2017). Based on the philosophy, principles and strategies of the Early Start Denver Model (ESDM), the G-ESDM is a manualized evidence-based early intervention that includes a set of strategies to adapt to the physical and social learning environment in order to support pupil participation in classroom activities and the school community at large. While the presence of students with Autism Spectrum Disorder (ASD) in Italian school settings represents a challenge for both special education scholars and teachers which has endorsed the paradigm of full inclusion, some reflections on the possibility of promoting the adoption of the G-ESDM in Italian preschools are required. This article outlines the main features of the G-ESDM models and concludes by illustrating a possible research itinerary for its implementation in the Italian educational system
Biochip detection of BP180 autoantibodies in blister fluid for the serodiagnosis of bullous pemphigoid: A pilot study
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