Characterisation of APC localisation, dynamics and functions at the centrosome

Adenomatous polyposis coli (APC) is a tumour suppressor protein and regulator of the wnt signalling pathway. APC is mutated in >90% of colorectal tumours and these mutations often translate a shorter truncated protein. Truncated APC has now been linked to mitotic spindle dysfunction. Mitotic spindles are nucleated from centrosomes and in cells expressing cancer mutant forms of APC cause aberrant spindle attachments leading to an increased rate of chromosome instability. Both full-length and mutant APC persistently localise to the centrosome throughout the cell cycle, however its role at interphase centrosomes are ill-defined. In this thesis, using a combination of immunofluorescence microscopy, retention assays and fluorescence recovery after photobleaching (FRAP) techniques, both wild-type and mutant forms of APC were found to be highly dynamic at the interphase centrosome, but highly retained at the mitotic centrosome, and targeted by the Armadillo domain of APC. Using various centrosome functional assays, APC was found to contribute to microtubule nucleation, but was not involved in centrosome amplification or separation. Using protein interaction methods, several novel APC binding partners ranging from protein regulators of the centrosome to microtubule-associated proteins were also discovered

Renal and Splenic Micro-Infarctions Following Bronchial Artery Embolization with Tris-Acryl Microspheres

A bronchial artery embolization (BAE) is an important therapeutic method used to control acute and chronic hemoptysis. We report a case of multiple micro-infarcts involving both the kidneys and spleen, following a BAE with 500-700 µm crossed-linked tris-acryl microspheres (Embospheres) in a patient with bronchial artery pulmonary vein shunts. The superior penetration characteristics of the microspheres may have resulted in the greater tendency to cross the bronchial artery pulmonary vein shunts, which subsequently caused the systemic infarcts in our patient. We propose the use of larger sized microspheres (700-900 µm), which may aid in avoiding this complication

An endoscopic modification of the simultaneous ‘above and below’ approach to large pituitary adenomas

Surgical resections of large-to-giant pituitary adenomas (PA) are technically challenging procedures. Tumors with a fibrous consistency or ‘hour-glass’ configurations are particularly difficult to remove completely and safely through the transsphenoidal route alone. Although the transcranial approach can facilitate the removal of a large suprasellar mass, it may be associated with significant bleeding within the intradural space. A simultaneous microscopic transcranial and transsphenoidal approach has been described as an alternative surgical strategy. We have further modified this ‘above and below’ approach by adopting endoscopic techniques for the transsphenoidal part of the procedure. This modified approach has the advantages of requiring only one operating microscope, and permitting freer maneuvers and easier orientation for both surgical teams. We present two patients successfully treated with this approach. Complete tumor removal was achieved and both patients achieved satisfactory functional recovery

A clinicopathological study of non-functioning pituitary neuroendocrine tumours using the World Health Organization 2022 classification

BackgroundThe 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET).MethodsA total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses.ResultsBased on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p<0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease.ConclusionThe 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis

Adjustment of children in single parent families: the mediating effect of self-disclosure

published_or_final_versionSocial Work and Social AdministrationDoctoralDoctor of Philosoph

Disabled employees and their employers: experiences of the employment of people with a physical disabilityin Hong Kong

published_or_final_versionSocial WorkMasterMaster of Social Wor

Hong Kong Renal Registry 1995–1999

AbstractThis report was based on the data from the Renal Registry of the Hospital Authority of Hong Kong, accounted for 90% to 95% of all the patients on renal replacement therapy (RRT) in Hong Kong. Patients who received RRT under the private sectors were not included in this report. The data were as of 31 March 1999.There were 11 renal units, five satellite centers and four major renal transplant centers. The number of patients on RRT was 4268 [627 patients per million (pmp)], of which 58% (2490 patients, 360 pmp) were on peritoneal dialysis (PD), 13% (576 patients, 85 pmp) on hemodialysis (HD) and 28% (1202 patients, 177 pmp) with functioning kidney transplants (TX). The net increase of the number of patients on RRT from previous year was 10%. The incidence of end-stage renal failure was 762 (112 pmp). The median age of the existing patients on RRT was 52, of which 33% were above the age of 61 years. The median age of the new patients was 56 years, of which 50% were above the age of 61 years. The major causes of renal failure for existing patients were glomerulonephritis 32%, unknown 26% and diabetes 21%. For the new cases, 34% were due to diabetic nephropathy. Of all the patients on RRT, 10% were serologically positive for hepatitis B infection while 6% were positive for hepatitis C infection.Of all the patients on dialysis, 81% were on PD, of which 92% were on continuous ambulatory peritoneal dialysis (CAPD). Of the CAPD patients, 13% were still using “connect” systems, 75% were using “disconnect” systems and 12% using UV flash systems. Nineteen percent of all the patients on dialysis were on HD, of which 54% were on hospital based HD, 21% on satellite center based HD, 9% on charitable center based HD and 3% on home HD. Of the 1202 patients with kidney transplants, 629 (52%) were transplanted in Hong Kong. Of these, 325 (52%) were cadaveric kidney transplantation. For the year ending 31 March 1999, 113 patients (17 pmp) received a kidney transplantation, of which 58 transplants were performed in Hong Kong (30 cadaveric kidneys and 28 living related kidneys). Thirty-one percent of all the patients on RRT were receiving erythropoietin therapy.The annual crude mortality rate for all RRT was 7% (8% for PD, 14% for HD and 1.6% with TX). The major causes of death were cardiovascular (24%), infection (22%) and cerebral vascular accident (6%). The 1 and 5 year patient survivals for kidney transplants performed in Hong Kong between 1 April 1993 to 31 March 1998 were 98%, 96% for living related kidney and 94%, 89% for cadaveric kidney. The 1 and 5 year graft survivals were 92%, 88% (censored), 91%, 85% (not censored) for living related kidney and 89%, 83% (censored), 86%, 79% (not censored) for cadaveric kidney. The overall peritonitis rate for all CAPD systems for the 7 months ending 31 March 1999 was one episode per 21 months. The peritonitis rate of the new disconnect systems was one episode per 20 to 27 months.The point prevalence rate of RRT (1997 data) for Hong Kong was within 15% range of that for Australia, Canada and most European countries, but only 40% to 60% of that for Japan, USA and Taiwan. The percentage of dialysis patients being treated with PD was highest in the world