Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion.

Background: Adoptive cell therapy (ACT) is a promising strategy for treating cancer, yet it faces several challenges such as lack of long-term protection due to T cell exhaustion induced by chronic TCR stimulation in the tumor microenvironment. One benefit of ACT, however, is that it allows for cellular manipulations, such as deletion of the phosphotyrosine phosphatase non-receptor type 22 (PTPN22), which improves CD8 T cell antitumor efficacy in ACT. We tested whether cytolytic T cells (CTLs) were also more effective than CTL in controlling tumors in scenarios that favor T cell exhaustion.

Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.

Early TCR signaling is dependent on rapid phosphorylation and dephosphorylation of multiple signaling and adaptor proteins, leading to T cell activation. This process is tightly regulated by an intricate web of interactions between kinases and phosphatases. A number of tyrosine phosphatases have been shown to modulate T cell responses and thus alter T cell fate by negatively regulating early TCR signaling.

Preparing medical students for clinical practice: easing the transition.

The transition from medical student to junior doctor is a challenge; the UK General Medical Council has issued guidance emphasizing the importance of adequate preparation of medical students for clinical practice. This study aimed to determine whether a junior doctor-led simulation-based course is an effective way of preparing final year medical students for practice as a junior doctor.We piloted a new 'preparation for practice' course for final year medical students prior to beginning as Foundation Year 1 (first year of practice) doctors.

Use of FDG PET/CT in identification of bone marrow involvement in diffuse large B cell lymphoma and follicular lymphoma: comparison with iliac crest bone marrow biopsy.

Background Non-Hodgkin's lymphoma (NHL) accounts for around 4% of new cancer cases annually. Bone marrow involvement is important for staging and management. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is used increasingly to identify this, in addition to bone marrow biopsy (BMB), which is seen as "gold" reference standard.

Negative 18F-FDG-PET-CT may exclude residual or recurrent disease in anal cancer.

Objectives: The incidence of anal cancer is increasing in Western countries. Fluorine-18 fluorodeoxyglucose (F-FDG) PET-computed tomography (CT) is used in the assessment of anal cancer, but its routine use is not established. The aim of this study was to assess the value of F-FDG-PET-CT in staging and post-treatment assessment in anal cancer and to determine its impact on management.

Gene Therapy for Pyoderma Gangrenosum: Optimal Transfection Conditions and Effect of Drugs on Gene Delivery in the HaCaT Cell Line Using Cationic Liposomes.

Background/aims: Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, currently treated empirically with immunosuppression. PG is a good target for gene therapy since the skin is easily accessible. This study used the FDA-approved vector Lipofectamine® 2000 to investigate in vitro transfection of skin keratinocytes.