Targeting the XPO1-dependent nuclear export of E2F7 reverses anthracycline resistance in head and neck squamous cell carcinomas.

Patient mortality rates have remained stubbornly high (40%) for the past 35 years in head and neck squamous cell carcinoma (HNSCC) due to inherent or acquired drug resistance. Thus, a critical issue in advanced SCC is to identify and target the mechanisms that contribute to therapy resistance. We report that the transcriptional inhibitor, E2F7, is mislocalized to the cytoplasm in >80% of human HNSCCs, whereas the transcriptional activator, E2F1, retains localization to the nucleus in SCC.

Sexual behaviour, HPV status and p16 expression in oropharyngeal and oral cavity squamous cell carcinomas: a case-case comparison study.

A significant proportion of mucosal squamous cell carcinomas of the head and neck (HNSCC; particularly of the oropharynx) are directly attributable to the human papillomavirus (HPV). The increase in the incidence of HPV-related tumours has been postulated to be due to changing sexual practices in the community. We analysed 136 formalin-fixed paraffin-embedded squamous cell carcinomas from the oral cavity (n=40) and oropharynx (n=96) recruited from the Princess Alexandra Hospital (Brisbane, Australia).

Predictors for secondary therapy after surgical resection of nonfunctioning pituitary adenomas.

Objective: Factors determining recurrence of nonfunctioning pituitary adenomas (NFAs) that require further therapy are unclear as are postoperative follow-up imaging guidelines. We aimed to identify predictors for secondary therapy after surgical resection of NFAs and use this knowledge to inform postoperative management.

Design And Patients: A single-centre retrospective study of surgically resected NFAs in 108 patients followed for up to 15 years.

Implementation and evaluation of amyloidosis subtyping by laser-capture microdissection and tandem mass spectrometry.

Background: Correct identification of the amyloidosis-causing protein is crucial for clinical management. Recently the Mayo Clinic reported laser-capture microdissection (LCM) with liquid chromatography-coupled tandem mass spectrometry (MS/MS) as a new diagnostic tool for amyloid diagnosis. Here, we report an independent implementation of this proteomic diagnostics method at the Princess Alexandra Hospital Amyloidosis Centre in Brisbane, Australia.

Low prevalence of human papillomavirus in oral cavity squamous cell carcinoma in Queensland, Australia.

Background: While human papillomavirus (HPV) is an accepted risk factor for oropharyngeal squamous cell carcinoma (SCC), its aetiological role in oral cavity SCC remains unclear. This study aimed to determine the HPV prevalence in an Australian population.

Methods: DNA was extracted from 63 formalin-fixed paraffin-embedded tumour specimens histologically confirmed as SCC of the oral cavity, diagnosed during 2006-2012.

RacGAP1 Is a Novel Downstream Effector of E2F7-Dependent Resistance to Doxorubicin and Is Prognostic for Overall Survival in Squamous Cell Carcinoma.

We have previously shown that E2F7 contributes to drug resistance in head and neck squamous cell carcinoma (HNSCC) cells. Considering that dysregulation of responses to chemotherapy-induced cytotoxicity is one of the major reasons for treatment failure in HNSCC, identifying the downstream effectors that regulate E2F7-dependent sensitivity to chemotherapeutic agents may have direct clinical impact. We used transcriptomic profiling to identify candidate pathways that contribute to E2F7-dependent resistance to doxorubicin.

Human papillomavirus status and p16(INK4A) expression in patients with mucosal squamous cell carcinoma of the head and neck in Queensland, Australia.

Background: The last decade has seen changes in the epidemiology of mucosal squamous cell carcinomas of the head and neck (HNSCCs), with increasing numbers of cases attributable to human papillomavirus (HPV) infection. We sought to determine the prevalence of HPV and p16(INK4a) expression in Australian HNSCC patients and to identify predictors of HPV-positivity.

Methods: We recruited 248 HNSCC patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx or larynx diagnosed between 2004 and 2010.

A novel E2F/sphingosine kinase 1 axis regulates anthracycline response in squamous cell carcinoma.

Purpose: Head and neck squamous cell carcinomas (HNSCC) are frequently drug resistant and have a mortality rate of 45%. We have previously shown that E2F7 may contribute to drug resistance in SCC cells. However, the mechanism and pathways involved remain unknown.

Hyperdiploid tumor cells increase phenotypic heterogeneity within Glioblastoma tumors.

Here we report the identification of a proliferative, viable, and hyperdiploid tumor cell subpopulation present within Glioblastoma (GB) patient tumors. Using xenograft tumor models, we demonstrate that hyperdiploid cell populations are maintained in xenograft tumors and that clonally expanded hyperdiploid cells support tumor formation and progression in vivo. In some patient tumorsphere lines, hyperdiploidy is maintained during long-term culture and in vivo within xenograft tumor models, suggesting that hyperdiploidy can be a stable cell state.

Radiation-induced primary cerebral atypical teratoid/rhabdoid tumour in an adult.

Atypical teratoid/rhabdoid tumours (ATRT) of the central nervous system are uncommon embryonal carcinomas that predominantly affect infants and young children, and less commonly adults. We report a 58 year old woman who presented with ATRT involving the right parietal lobe which was treated with surgery and adjuvant radiotherapy. Her history was significant for soft tissue sarcoma of the right ear treated with surgery and adjuvant radiotherapy at age 3, thus raising the possibility of radiation-induced aetiology.