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H Y Leung

Publications and source records attributed to H Y Leung.

18 recordsLinked to original sources
PubMed1999

FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease.

Identification of prostate cancers at high risk of progression is difficult and a better understanding of how peptide growth factors influence cellular function might be useful. Fibroblast growth factors (FGFs) have been implicated in prostate cancer development. FGF8 was identified in the Shionogi mouse mammary carcinoma SC-3 cell line as an androgen-induced mitogen. We tested if FGF8 was over-expressed in human prostate cancer and if its expression correlated with clinical data and outcome. One hundred and six cases of prostate cancer and ten cases of BPH were examined. In situ hybridization was employed to detect FGF8 mRNA expression, which was identified within the malignant prostatic epithelium in 85/106 (80.2%) cases. Increased expression of FGF8 correlated significantly with higher Gleason scores (P=0.0004) and advanced tumour stage (P=0.0016). Using immunohistochemistry, we confirmed over-expression of the FGF8b isoform. Men with tumours which expressed high levels of FGF8 had worse survival (P=0.034), although FGF8 mRNA was not able to provide additional prognostic information in a multivariate analysis. Additionally, FGF8 expression was shown to persist in androgen independent prostate cancer. Using a range of normal adult tissues, FGF8 expression was restricted to neurones and the germinal epithelium in addition to the prostate. In vitro studies demonstrated that in the presence of neutralizing antibody to FGF8b there was significant inhibition of prostate cancer cell growth, confirming the biological significance of FGF8 in prostate carcinogenesis.

Adult↗
PubMed1999

aFGF immunoreactivity in prostate cancer and its co-localization with bFGF and FGF8.

Fibroblast growth factors (FGFs) have been implicated in the development of numerous malignancies including prostate cancer. In a pilot study it has been shown that FGF8 mRNA is up-regulated in prostate cancer. The aim of the present study was to determine whether aFGF and bFGF were co-expressed with FGF8 in human prostate cancer. Twenty-nine cases of prostate cancer of different histological grades were examined. Immunohistochemical analysis was employed to study aFGF and bFGF expression. In the light of the results, aFGF immunoreactivity was studied in a further 43 cases. aFGF and bFGF immunoreactivity was identified in the cytoplasm of the malignant prostatic epithelium. aFGF was overexpressed in 62/72 (86.1 per cent) cases and bFGF in 19/29 (65.5 per cent). High levels of aFGF immunoreactivity were noted in areas of high-grade prostatic intraepithelial neoplasia (PIN). In this series, aFGF immunoreactivity was most commonly observed and correlated closely with Gleason score and tumour stage ( p=0.007 and 0.007, respectively). Co-localization of aFGF, bFGF, and FGF8 was detected in 9/29 (31.0 per cent) cases. There was a significant correlation between aFGF and FGF8 expression. In conclusion, aFGF, bFGF, and FGF8 are co-localized in human prostate cancer; they may have a synergistic effect in prostate cancer growth and progression.

Aged↗
PubMed1999

Skin carriage of acinetobacters in Hong Kong.

We studied the carriage of Acinetobacter spp. at five superficial sites in 79 patients from two hospitals, in 133 healthy controls from the community (medical students and new nurses), and in 198 student nurses in different classes. A total of 431 isolates from 364 positive sites of 201 subjects and 124 blood culture isolates (1997 to 1998) were genospeciated by amplified ribosomal DNA restriction analysis. Genospecies 3 was the most common species. The carriage rate of student nurses (42 of 131) was significantly lower than that of new nurses from the community (25 of 38) (chi-square test, P = 0.0004; odds ratio [OR], 4.08; 95% confidence limits, 1.78 to 9.41) but not significantly different (P = 0.1) from that of patients in the same hospital (20 of 42). Genospecies from blood cultures and subjects (acute patients and student nurses) from Prince of Wales Hospital were similar to one another but different from subjects from the community or from another hospital (chi-square test, P < 0.0001). Half of the subjects who were positive at at least two sites had different genospecies. Of the 28 sites examined, 68% showed strain variation among isolates of the same genospecies by random amplified polymorphic DNA analysis. Half of the 106 subjects who had samples taken again within 6 weeks or 6 months later were positive only once. In the 17 subjects who were positive on at least two occasions, each occasion yielded different genospecies in 13 subjects. Our results indicate that skin carriage in the majority of healthy subjects is characterized by low density, variation in genospecies and strains, short-term duration, and the typicality of a given locality.

Acinetobacter↗
PubMed1998

Bowel dysfunction after bladder reconstruction.

PURPOSE: Bowel function may be disturbed after intestinal segments are used in urinary reconstruction. The etiology of this condition and its incidence in different patient groups is unclear. We studied the incidence of bowel disturbance in patients who underwent bladder replacement, continent diversion, enterocystoplasty for idiopathic detrusor instability and ileal conduit diversion. MATERIALS AND METHODS: We evaluated 71 patients after ileal conduit diversion and 82 after bladder reconstruction, including clam enterocystoplasty for detrusor instability in 28, neurogenic bladder dysfunction in 26 and nonneuropathic conditions in 28. We noted the severity of symptoms, such as frequency of defecation, nocturnal diarrhea, flatus leakage, fecal urgency, fecal incontinence and explosive diarrhea, as well as quality of life. RESULTS: Of the patients who underwent bladder reconstruction 24% had symptoms of bowel dysfunction preoperatively and 42% of those who were asymptomatic preoperatively described new bowel symptoms postoperatively. These symptoms were most common and severe in 54% of patients after clam enterocystoplasty for detrusor instability compared to 26% with neuropathy, 14% with a nonneuropathic condition and 15% with an ileal conduit. Compared to those in other groups patients who underwent enterocystoplasty for detrusor instability had a significantly higher incidence of nocturnal bowel movements (18 versus less than 4%, p <0.01), flatus leakage (29 versus less than 8%, p <0.01), fecal urgency (39 versus less than 12%, p <0.001) and fecal incontinence (32 versus less than 16%, p <0.001). The length of ileum used for clam enterocystoplasty was only slightly greater than that used for ileal conduit operations (25 versus 18 cm.). Of the patients who underwent enterocystoplasty for detrusor instability 29% regretted undergoing the procedure due to subsequent bowel symptoms. CONCLUSIONS: After enterocystoplasty for detrusor instability patients are at risk of significant bowel symptoms. The development of new bowel symptoms was associated with poor patient satisfaction.

Adult↗
PubMed1997

Keratinocyte growth factor expression in hormone insensitive prostate cancer.

Cellular interactions between stroma and epithelium are important in the growth and proliferation of prostate cancer. Peptide growth factors may facilitate the progression of prostate cancer as autocrine and/or paracrine factors. Keratinocyte Growth Factor (KGF or FGF7) has a differentiative and proliferative effect on the epithelium of the developing rat prostate. We investigated if KGF may act as a paracrine agent in human prostate cancer and examined the expression of KGF and Fibroblast Growth Factor Receptors (FGFRs) (IIIb and IIIc isoforms of the FGFR1 and FGFR2 genes). Sixty-five percent (11 out of 17 informative cases) of prostate cancers (CaP) expressed KGF mRNA by RT-PCR, while KGF expression was not detected in benign prostatic hyperplasia (BPH) (n = 6). Upregulation of KGF expression was related to hormone insensitive tumours (P<0.05). Tumour grade and stage were not associated with KGF expression. The source of KGF expression was further characterised using an in vitro primary culture model, showing its restriction to the prostatic stroma. The FGFR1IIIb isoform was expressed in all cases of prostate cancer (n = 17), and FGFR1IIIc mRNA was not detected. In the BPH group, FGFR1IIIb transcripts were detected in four out of six cases. FGFR2IIIb expression was detected in five of six cases of BPH and twelve out of seventeen (71%) cases of prostate cancer. In CaP, though not reaching statistical significance, the persistence of FGFR2IIIb expression appeared to be associated with hormone insensitive tumours (P=0.052). FGFR2IIIc expression was present in eleven of seventeen tumours but was absent in all six cases of BPH. Functional assessment of recombinant KGF in a proliferation assay demonstrated a mitogenic effect of up to 100% on cultured prostatic epithelial cells.

Androgens↗
PubMed1997

Alu-polymerase chain reaction genomic fingerprinting technique identifies multiple genetic loci associated with pancreatic tumourigenesis.

DNA fingerprinting can be used to detect genetic rearrangements in cancer that may be associated with activation of oncogenes and inactivation of tumour suppressor genes. We have developed a fingerprinting strategy based on polymerase chain reaction (PCR) amplification of genomic DNA with primers specific for the Alu repeat sequences, which are highly abundant in the human genome. This has been applied to DNA from pancreatic cancer and paired normal samples to isolate and identify fragments of genomic DNA rearranged in the malignant cells. These fragments have been sequenced and used as probes to isolate hybridising clones from gridded bacteriophage P1, phage artificial chromosome, and cosmid libraries for fluorescent in situ hybridisation mapping and the identification of expressed sequences. Further characterisation has identified a putative novel gene (ART1) that is up-regulated specifically in pancreatic cancer as well as another sequence with similarity to genes involved in differentiation (POU domains). In conclusion, we suggest that Alu-PCR fingerprinting may be a useful technique for the identification of genes involved in tumourigenesis.

Blotting, Southern↗
PubMed1997

Serum free prostate-specific antigen in the diagnosis of prostate cancer.

OBJECTIVE: To determine the value of the ratio of free prostate-specific antigen (fPSA) to total PSA (tPSA) in the diagnosis of benign prostatic hyperplasia (BPH) and prostate cancer in a cohort of patients undergoing prostatic transrectal ultrasonography (TRUS). PATIENTS AND METHODS: The study comprised 153 patients (99 with BPH and 54 with prostate cancer) undergoing diagnostic TRUS of the prostate. Patients with a tPSA of > 30 ng/mL were excluded from analysis. Free PSA was assayed using an immunoassay specific for unbound PSA (CanAg Diagnostics, Sweden). Total PSA was measured using the HybriTech Tandem-R PSA immunoradiometric assay in routine clinical use and this estimate was validated using the CanAg tPSA assay. RESULTS: The measurements of tPSA from both assay systems correlated closely. The f/tPSA ratios in patients with prostate cancer were significantly lower than in those with BPH (median values 0.152 and 0.2, respectively, P<0.01). In patients with prostate cancer, the median f/t PSA levels apparently declined with increasing tPSA levels but in those with BPH, the levels of tPSA were not significantly associated with the f/tPSA ratio; the ratios did not vary significantly with age in either group. A f/tPSA ratio at a threshold of 0.16 had positive and negative predictive values of 44% and 74%, respectively; the corresponding values for a tPSA of > 4 ng/mL were 30% and 52%. CONCLUSION: The f/tPSA ratio differs significantly between patients with BPH and cancer but because there is a considerable overlap of f/tPSA ratios between the groups, f/tPSA values alone were not sufficiently specific to be used as a single diagnostic test.

Biopsy↗
PubMed1997

A potential autocrine loop between heregulin-alpha and erbB-3 receptor in human prostatic adenocarcinoma.

OBJECTIVE: To examine the expression of heregulin-alpha (a new member of the epidermal growth factor family) and its receptor erbB-3 in human prostate cancer by immunohistochemistry, and to analyse their implication for clinical outcome. PATIENTS AND METHODS: Using specific anti-peptide antibodies, tumour samples from 50 consecutive patients with newly diagnosed prostate cancer (18 well, 15 moderately and 17 poorly differentiated) and four patients with benign prostatic hyperplasia (BPH) were immunostained for heregulin-alpha (an isoform of heregulin) and erbB-3 proteins. Representative areas from each case were used to assess immunoreactivity. RESULTS: Heregulin-alpha was expressed (i.e. > or = 10% of tumour cells positive) in 36 (72%) and erbB-3 in 27 (54%) of the 50 cases. High levels of expression of heregulin-alpha (> 90% of tumour cells stained) appeared to be related to high-grade tumours, but the association did not reach statistical significance. There was no correlation between the levels of expression of erbB-3 and tumour grade. All four samples from BPH stained negatively for heregulin-alpha and erbB-3. Fourteen patients had bony metastases identified by bone scintigraphy and all received androgen ablation after undergoing transurethral resection of the prostate. Immunoreactivity for heregulin-alpha and erbB-3 were absent in five cases, all of whom responded to hormone manipulation and remained symptom-free at the time of review (mean follow up 3 years, range 2-4). Despite hormone manipulation, the nine patients overexpressing heregulin-alpha and/or erbB-3 died during a mean follow up of 2.5 years (range 0.5-4). CONCLUSION: The overexpression of heregulin-alpha and erbB-3 in prostate cancer is detectable by immunostaining. Activation of the type 1 growth-factor receptor system by heregulin-alpha and/or the erbB-3 receptor appears to be associated with a less favourable prognosis in advanced disease.

Adenocarcinoma↗
PubMed1996

The role of the nurse practitioner in a urology service.

OBJECTIVE: To evaluate the role of the nurse practitioner in urology and to determine the impact on the work of junior doctors. METHODS: Written criteria were defined before the postholder was appointed and subsequent performance was assessed against these criteria. Training was provided and the quality of work was assessed by direct observation. Senior House Officers (SHOs) were asked whether the post had increased their opportunities to attend theatre, outpatients and post-graduate training sessions and had decreased the number of 'inappropriate' tasks they had to perform. RESULTS: The nurse practitioner accomplished all the tasks that were defined before the appointment. The assessment of patients in pre-admission and haematuria clinics was satisfactory. The continuity of information, care of patients and counselling for patients receiving complex surgery were improved. Sixty-three per cent of all patients seen in the pre-admission clinic and all patients in a haematuria clinic were assessed initially by the nurse practitioner. Because the nurse practitioner was involved in setting up intravenous drug administration and infusions, administrative tasks and in obtaining results from the laboratory, the number of 'inappropriate' tasks performed by the SHOs decreased and they were able to attend more sessions of training and education. CONCLUSIONS: The nurse practitioner in clinical urological practice constitutes an effective use of resources and relieves junior medical staff from other tasks, allowing them to receive a more focused training. In addition, the quality of patient care was thought to be improved in some areas. The framework of a job plan for a nurse practitioner is described.

Humans↗
PubMed1996

Bladder cancer.

Bladder cancer is the fourth most common cancer in England and Wales. The most common presenting symptom is macroscopic haematuria. The management options for superficial and invasive bladder cancer depend on the stage at presentation. Most superficial bladder cancers are managed by transurethral resection and cytoscopic follow-up. The prognosis for patients with invasive bladder cancer is less good. The role of chemical, radiotherapeutic and surgical intervention are discussed.

Antineoplastic Agents↗
PubMed1994

Expression and functional activity of fibroblast growth factors and their receptors in human pancreatic cancer.

We have analysed expression of the first 7 members of the family of heparin-binding fibroblast growth factor (FGFs) and their 4 high-affinity receptors (FGFRs) in human pancreatic carcinoma cell lines, both at the mRNA and protein levels. In cell lines expressing FGFRs, 2 typical patterns were observed: (i) expression of FGFR-I, -3 or -4 along with the expression of at least one FGF; (ii) co-expression of FGFR-3 and FGFR-4 in the absence of FGF expression. Using RT-PCR, transcripts representing multiple isoforms of both extracellular and intracellular domains of FGFR-I were detected in the cell line PT45. A novel extracellular domain variant of FGFR-I was predicted to encode the first immunoglobulin loop in a potentially secreted form. Protein expression of the splice variants of FGFR-I was confirmed by immunoprecipitation with specific antibodies in radiolabelled ligand cross-linking experiments. The type I carboxyl end and the alpha subtype extracellular domain were detected in the PANC-I cell line, while the type I carboxyl terminus and the gamma subtype extracellular domain were expressed in the PT45 cell line. Expression of FGF-2 in PT45 was also detected by immunoprecipitation using 3 different anti-FGF-2 antibodies. Apart from the 18-kDa product, higher molecular weight isoforms, namely 22- and 23-kDa isoforms, were expressed. In an assay of anchorage-independent growth, exogenous FGF-2 stimulated a maximum 15-fold and 10-fold increase in colony formation by the cell lines MIA PACA-2 and PANC-I respectively. Treatment of monolayer cultures of the same cell lines did not promote growth. However, a specific neutralising antibody against FGF-2 reduced cell proliferation of MIA PACA-2 cells by 50%.

Base Sequence↗