72 research outputs found
TCRγ-Chain Gene Rearrangement by PCR-Based GeneScan: Diagnostic Accuracy Improvement and Clonal Heterogeneity Analysis in Multiple Cutaneous T-Cell Lymphoma Samples
Cutaneous T-cell lymphomas are a heterogeneous group of lymphomas where the tumor population emerges within a multiple subclone pattern (“clonal heterogeneity”). PCR analysis has been shown to be useful in the diagnosis of mycosis fungoides (MF) and Sézary Syndrome (SS). Focusing the attention on clonal heterogeneity, the efficacy of the multiplex/heteroduplex (HD) PCR and the GeneScan (GS) capillary electrophoresis analysis was compared in the early diagnosis of MF/SS, using a multiple sample approach. Indeed, GS demonstrated TCRγ gene rearrangement (GR) in all the 57 SS (100%) and in 123/146 (84%) of the MF samples, whereas the multiplex/HD PCR was less sensitive. An increase in clonality was observed in connection with both a worsening of the cutaneous disease (79% T1/T2; 100% T3/T4) and an increase in the histopathological score (HS<5, 76%; HS≥5, 94%). Clonal heterogeneity with adjunctive reproducible skin TCRγ-GRs was also observed. “Clonal instability,” with different GRs, was present in a small percentage of patients. Therefore, it can be concluded that GS analysis in TCRγ-GR is able to improve diagnosis in MF/SS patients and the multiple sample approach is helpful for a correct interpretation of clonal patterns in skin lesions, especially in early-stage MF and in SS skin/blood samples
Preparing an interdisciplinary guidance for the management of generalised paediatric status epilepticus
BACKGROUND: A guidance was created to assist family doctors
in managing generalized paediatric status
epilepticus (GPSE) at Primary HealthCare (PHC)
clinics.AIM: The article aims to discuss the process by which
the GPSE guidance was prepared.OBJECTIVES: The authors intend to provide information on
how the literature review was carried out, what
clinical threshold was decided as appropriate
for the administration of rescue medication, and
what treatments may be used in PHC.METHOD: An initial search and guidance draft was
forwarded to a Joint Working Group (JWG)
composed of professionals working at PHC
and Mater Dei Hospital (MDH). The names of
benzodiazepines and their formulations available
at PHC clinics were forwarded to the JWG by the
clinical Chairperson of Primary HealthCare. A
Pubmed search was carried out for the terms
“status epilepticus,” “children”, and “prehospital”,
filtering for free full text publications, humans,
English language, and dating from 1999 to 2019, yielding seventeen results in the English
language. Eight were relevant. A second Pubmed
search for “diazepam use in paediatric seizures”
and “midazolam use in paediatric seizures”
yielded fifty-five results, filtering for English
and dating from 2010-2019. Two were relevant.
Several guidelines and literature were directly
referenced. The literature review process and
results were summarised and modified into a
flowchart.RESULTS: An interdisciplinary approach was used to
decide how GPSE should be treated. Consensus
was agreed that if a seizure lasts more than
five minutes, benzodiazepines midazolam and
diazepam available at PHC clinics, may be used.
Intramuscular, intranasal, buccal, or rectal routes
are preferred per the child’s weight; and time the
duration of seizure activity.CONCLUSION: GPSE may terminate during the first five minutes
of ictal activity. Midazolam and diazepam may be
administered by different methods if seizures
persist, depending on the clinical scenario.peer-reviewe
Development and characterisation of acquired radioresistant breast cancer cell lines
Table S1. RIN values for all samples used in gene expression analysis. (XLSX 10 kb
Peripheral ENO1-specific T cells mirror the intratumoral immune response and their presence is a potential prognostic factor for pancreatic adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with an average survival of 4-6 months following diagnosis. Surgical resection is the only treatment with curative intent, but resectable PDAC patients are in the minority. Also, unlike other neoplasms, PDAC is resistant to conventional and targeted chemotherapy. Innovative treatments, such as immunotherapy, can be very important and the study of the immune response is fundamental. We previously demonstrated that PDAC patients show tumor-infiltrating T cells specific to a-enolase (ENO1), a glycolytic enzyme over expressed by pancreatic tumor cells, which plays an important role in promoting cell migration and cancer metastasis. In the present study, we evaluate the functional anticancer proprieties of ENO1-specific T cells isolated from the peripheral blood of PDAC patients. Furthermore, comparing the T cell receptor repertoire of ENO1-specific peripheral and infiltrating tumor T cells from the same patient suggests that ENO1-specific T cells, despite having a different functional profile, can recirculate from the tumor to the periphery. Finally, of clinical relevance, the presence of peripheral ENO1-specific T cells has a prognostic value and significantly correlates with a longer survival
The EGFR family members sustain the neoplastic phenotype of ALK+ lung adenocarcinoma via EGR1.
In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term RTK inhibition leads invariably to acquired resistance, tumor recurrence and metastatic dissemination. In ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several RTKs, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. Moreover, the engagement of wild-type epidermal growth factor receptor or MET receptors could sustain cell viability through early growth response 1 (EGR1) and/or Erk1/2; Akt activation and EGR1 overexpression prevented cell death induced by combined ALK/RTK inhibition. Membrane expression of ERBB2 in a subset of primary naive ALK+ NSCLC could be relevant in the clinical arena. Our data demonstrate that the neoplastic phenotype of ALK-driven NSCLC relays ‘ab initio' on the concomitant activation of multiple RTK signals via autocrine/paracrine regulatory loops. These findings suggest that molecular and functional signatures are required in de novo lung cancer patients for the design of efficacious and multi-targeted ‘patient-specific' therapies
The atypical 'hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2
ACKNOWLEDGEMENTS We would like to thank: Prof. Christophe Mulle, University of Bordeaux, France for the generous donation of the GluK2-Neo mice; Prof. Roberto Pellicciari and Prof. Maura Marinozzi, University of Perugia, Italy for the generous gift of PCCG-13; the Microscopy and Histology core facility at the Institute of Medical Sciences, University of Aberdeen for their support and assistance in some of the imaging in this work. We would also like to thank Prof. Gernot Riedel, University of Aberdeen UK and Prof. David Jane, University of Bristol UK for helpful comments during the work and discussion about drafts of this manuscript.Peer reviewedPublisher PD
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