Implementation of these guidelines in the daily practice of radiation oncology should contribute to reduce treatment variations from clinicians to clinicians, facilitate the conduct of multi-institutional clinical trials, and contribute to improved care of patients with head and neck carcinoma.
The HOX and PBX gene families encode transcription factors that have key roles in establishing the identity of cells and tissues in early development. Over the last 20 years it has become apparent that they are also dysregulated in a wide range of solid and haematological malignancies and have a predominantly pro-oncogenic function. A key mode of transcriptional regulation by HOX and PBX proteins is through their interaction as a heterodimer or larger complex that enhances their binding affinity and specificity for DNA, and there is growing evidence that this interaction is a potential therapeutic target in malignancies that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma, and acute myeloid leukaemia. This review summarizes the roles of HOX and PBX genes in cancer and assesses the therapeutic potential of HOX/PBX dimer inhibition, including the availability of biomarkers for its application in precision medicine.
BACKGROUND Following allotransplantation, renal ischemia-reperfusion (I/R) injury initiates a series of events that provokes counter-adaptive immunity. Though T cells clearly mediate allospecific immunity, the manner in which reperfusion events augment their activation has not been established. In addition, comprehensive analysis of I/R injury in humans has been limited. METHODS To evaluate the earliest events occurring following allograft reperfusion and gain insight into those factors linking reperfusion to alloimmunity, we examined human renal allografts 30 to 60 minutes postreperfusion (n=10) and compared them with allografts with normal function that had resolved their I/R injury insult (>1 month posttransplant, n=6) and to normal kidneys (living donor kidneys before procurement, n=8). Biopsies were processed both for immunohistochemical analysis as well as for transcript analysis by real-time quantitative polymerase chain reaction (RT-PCR). RESULTS Reperfusion injury was characterized by increased levels of gene transcripts known to be involved in cellular adhesion, chemotaxis, apoptosis, and monocyte recruitment and activation. T-cell-associated transcripts were generally absent. However, recovered allografts exhibited increased levels of T-cell and costimulation-related gene transcripts despite normal allograft function. Consistent with these findings, the immediate postreperfusion state was characterized histologically by tubular injury and monocyte infiltration, while the stable posttransplant state was notable for T-cell infiltration. CONCLUSIONS These data suggest that monocytes and transcripts related to their recruitment dominate the immediate postreperfusion state. This gives way to a T-cell dominant milieu even in grafts selected for their stable function and absence of rejection. These data have implications for understanding the fundamental link between I/R injury and alloimmunity.
Senescing oral dysplasias are not immortalized by ectopic expression of hTERT alone without other molecular changes, such as loss of INK4A and/ or retinoic acid receptor-b: but p53 mutations are not necessarily required
Objectives: Odontogenic tumours (ODTs) are a heterogeneous group of lesions derived from elements of the tooth-forming tissues. There are no published detailed data on the incidence of odontogenic tumours in the UK. Aim: to retrospectively describe the range and incidence of odontogenic tumours from 1992-2016 in a single specialist unit and to compare this with other populations. Study Design: Using the Oral and Maxillofacial Pathology database, Sheffield, both local and referred consultation cases were included. A proportion of diagnoses were re-classified in accordance with the 2017 WHO classification. Results: In total, 559 odontogenic tumours were diagnosed. Overall, the most common lesions were ameloblastoma (196; 33.8%), odontome (148; 25.5%) and odontogenic myxoma (37; 6.3%), but this varied between local and referral case populations, with odontomes most common in the local population (43%). The sites affected, gender and age of patients were similar to other western populations. Malignant ODTs comprised 33 cases (5.7%), of which nine (27.3%) were ameloblastic carcinoma. The majority of the malignant ODTs were referral cases. Conclusions: These are the first detailed data on odontogenic tumours within a UK population and the pattern of incidence from the local population is similar to other western populations. The exceptional rarity of malignant ODTs emphasises the need for specialist centres in order to gain diagnostic experience.
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