Peter S.F. Chan

Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom.

Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto‐oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans.

Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin.

The flavonoid baicalin (baicalein 7-D-beta-glucuronate), isolated from the dried root of Scutellaria baicalensis Georgi (Huang Qin), is widely used in the traditional Chinese herbal medicine for its anti-inflammatory, anti-pyretic and anti-hypersensitivity effects. In the present study, we investigated the in vitro effects of baicalin on the growth, viability, and induction of apoptosis in several human prostate cancer cell lines, including DU145, PC-3, LNCaP and CA-HPV-10. The cell viability after treating with baicalin for 2-4 days was quantified by a colorimetric 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-s ulfophenyl)- 2H-tetrazolium (MTS) assay. The results showed that baicalin could inhibit the proliferation of prostate cancer cells. The responses to baicalin were different among different cell lines, with DU145 cells being the most sensitive and LNCaP cells the most resistant. Baicalin caused a 50% inhibition of DU145 cells at concentrations of 150 microM or above. The inhibition of proliferation of prostate cancer cells after a short period of exposure to baicalin was associated with induction by apoptosis, as evidenced by the typical nuclear fragmentation using Hoechst 33258 staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) labeling, DNA fragmentation, activation of caspase-3 and cleavage of poly-ADP-ribose polymerase (PARP). The results indicate that baicalin has direct anti-tumor effects on human prostate cancer cells.

Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients

High frequency loss of 3p21.3 region where RASSF1A located was demonstrated in several tumors. We aimed to investigate the methylation status of RASSF1A and the frequency of LOH in 3p21.3 region in bladder cancer. Three bladder cancer cell lines, 40 cases of bladder TCC and 14 cases of paired voided urine samples were subjected to methylation analysis. By methylation specific PCR, complete methylation of promoter region of RASSF1A gene were detected in cell lines T24 and UMUC3. Demethylation treatment re‐expressed RASSF1A in these 2 cell lines. Methylation of RASSF1A was also detected in 47.5% (19/40) of the TCC cases but not in 6 carcinoma in situ (CIS) or 6 normal urothelium samples. For LOH study, loss of 3p21.3 region was detected in 57.9% (11/19) of our cases. Interestingly, methylation of RASSF1A was found in 72.7% (8/11) of the cases with LOH but only in 12.5% (1/8) of the cases without LOH. Methylation of RASSF1A was detected in 50% (7/14) of voided urine samples, but not in normal control. It showed a higher sensitivity than conventional urine cytology in detecting cancer cells, especially for low grade cases. In conclusion, our results demonstrated a high frequency of RASSF1A methylation with frequent LOH in 3p21.3 region in bladder cancer. It suggested that it may be a potential tumor suppressor gene in this chromosomal region and can be silenced by promoter hypermethylation. Detection of aberrant gene methylation in routine voided urine was feasible and may provide a non‐invasive and sensitive approach for cancer detection.

Measurement and metabolism of isoflavonoids and lignans in the human male

Asian men, who consume a low fat/high fibre soya-based diet, have very much lower incidence of prostate cancer than men from North America and Europe. The soya bean is a rich source of the isoflavonic phyto-oestrogens, daidzein, genistein and equol, compounds which may be cancer-protective in Asian populations. The lignans, enterolactone and enterodiol, plant oestrogens derived from cereals and vegetables, may act in a similar manner in vegetarian men. We report here on the measurement of isoflavonoids and lignans, by gas chromatography-mass spectrometry, in prostatic fluid of men from Asia and Europe and also on the metabolism of these compounds in Western men following dietary supplementation.

In situ hybridization study of PSP94 (prostatic secretory protein of 94 amino acids) expression in human prostates

The prostatic secretory protein of 94 amino acids (PSP94), also named β‐microseminoprotein, is one of the major proteins secreted by the human prostate. However, its value as a prognostic marker for prostate cancers is still under debate. The aim of the present study was to examine the expression pattern of this protein in fetal, pubertal, and aged human prostates.

PSP94 (or β‐microseminoprotein) is a secretory protein specifically expressed and synthesized in the lateral lobe of the rat prostate

Prostatic secretory protein of 94 amino acids (PSP94), also called β‐microseminoprotein, is a small, nonglycosylated protein, rich in cysteine residues. It was first isolated as a major protein from human seminal plasma. Subsequently, its homologous proteins were identified, and their cDNAs or genes have been cloned in primates, pigs, and rodents.

17-year follow-up of a randomized prospective controlled trial of adjuvant intravesical doxorubicin in the treatment of superficial bladder cancer

PURPOSE To evaluate the efficacy of adjuvant intravesical doxorubicin in superficial transitional cell carcinoma of the urinary bladder on long-term follow-up. MATERIALS AND METHODS Between July 1986 and November 1991, all patients harboring superficial bladder cancers (Ta or T1) with one or more of these criteria (stage>a, grade>1, size>1 cm, multiple or recurrent tumors) were randomized to receive either 50 mg doxorubicin or no adjuvant therapy. Patients with recurrences were allowed to receive doxorubicin or other intravesical agents. Recurrence, progression and survival were analyzed. RESULTS There were 82 patients included (64 males and 18 females). The mean age was 64 years. Forty-six patients were randomized to the doxorubicin group and 36 to the control group. Final analysis was made at median follow-up of 45, 128 and 131.5 months for recurrence, progression and survival, respectively. Recurrence free, progression free and disease specific survival did not differ significantly between groups. The 10-year Kaplan-Meier estimates for recurrence free, progression free and disease specific survival were 67%, 84% and 92%, respectively for the doxorubicin group, and were 50%, 89% and 97%, respectively for the control group. Tumor size predicted recurrence (p=0.013) and grade predicted progression (p=0.004) with multivariate analysis. CONCLUSIONS Adjuvant intravesical doxorubicin could not be shown to improve recurrence, progression and survival of superficial bladder cancer, compared with control on long-term follow-up. Tumor size and grade were shown to be prognostic factors for recurrence and progression, respectively.

Identification of differently expressed genes in chemical carcinogen-induced rat bladder cancers

Possible altered gene expression patterns in bladder tumour carcinogenesis in rat bladder cancers induced by BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] was examined by cDNA microarray analysis of gene expression profiles. Thirty Sprague-Dawley rats were given drinking water containing 0.05% BBN ad libitum for 24 to 28 weeks. Equal numbers of control rats were given tap water without BBN. After treatment, the rat bladders were excised for RNA extraction and histopathological examinations. Total RNAs were extracted from rat transitional cell carcinoma (TCC) tissues and micro-dissected normal rat bladder epithelia. The atlas glass rat microarray was used, which included oligonucleotides of 1081 rat genes. Some of the up-regulated genes in rat bladder TCCs were further confirmed by Northern blotting. Our results showed that the transcriptions of 30 genes were significantly elevated in the rat bladder TCCs, and these included fly proto-oncogene, Lipocortin 2, COX IV, COX V a, and cathepsin D. Also, 15 genes were significantly down-regulated in the rat bladder TCCs and they included B7.1, TNFr1, APOA1 and VHL. The results of cDNA microarray analysis demonstrated that normal rat bladder epithelia and bladder TCC exhibited different and specific gene statement profiles. The increased expressions of the identified genes may play an important role in the chemically induced bladder carcinogenesis.SummaryPossible altered gene expression patterns in bladder tumour carcinogenesis in rat bladder cancers induced by BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] was examined by cDNA microarray analysis of gene expression profiles. Thirty Sprague-Dawley rats were given drinking water containing 0.05% BBN ad libitum for 24 to 28 weeks. Equal numbers of control rats were given tap water without BBN. After treatment, the rat bladders were excised for RNA extraction and histopathological examinations. Total RNAs were extracted from rat transitional cell carcinoma (TCC) tissues and micro-dissected normal rat bladder epithelia. The atlas glass rat microarray was used, which included oligonucleotides of 1081 rat genes. Some of the up-regulated genes in rat bladder TCCs were further confirmed by Northern blotting. Our results showed that the transcriptions of 30 genes were significantly elevated in the rat bladder TCCs, and these included fly proto-oncogene, Lipocortin 2, COX IV, COX V a, and cathepsin D. Also, 15 genes were significantly down-regulated in the rat bladder TCCs and they included B7.1, TNFr1, APOA1 and VHL. The results of cDNA microarray analysis demonstrated that normal rat bladder epithelia and bladder TCC exhibited different and specific gene statement profiles. The increased expressions of the identified genes may play an important role in the chemically induced bladder carcinogenesis.