Further Analytical Studies on a Mercuri Thiol Adduct Isolated from a Human Prostate Cancer Cell Line (LNCaP)

Thiols play vital roles in cellular metabolism knowledge of which may be important in the design of future anticancer drugs. Previous work on the composition of the thiols present in human cancer cell lines has shown the presence of an unknown low molecular weight species, deemed to be a “Conthiol”, which could be important in this respect. This was prepared and isolated from a human prostate cancer cell line (LNCaP) in the form of an adduct of 2-mercuri-4-nitrophenol;it accounts for 56.5% of the total cellular thiols present in this cell line. Initial LC-MS analysis of this adduct had indicated that the possible molecular weight of the thiol was in the region of 467 daltons. In further analytical studies to identify the thiol, attempts were made to release it from the adduct by passage through a Thiopropyl Sepharose6B column. LC-MS analysis of the column eluate revealed two components yielding negative ion fragments of 427 m/z and 449 m/z. Only the former component contained thiol, indicating that a breakdown and/or possible rearrangement of the Conthiol had occurred. Further investigations of the column thiol eluate using ICP-MS analysis showed that the sulfur content agreed with the spectrophotometric analysis result (Ellman assay) and that the molecule did not contain phosphate. Amino acid analyses of the eluate were negative. In an attempt to prevent the breakdown of the thiol released by the Thiopropyl Sepharose 6B column, the adduct was treated with 5% v/v bromine water prior to applying to the column. In this instance the thiol containing eluate obtained from the column was treated with an equimolar quantity of mercuric chloride forming a fresh adduct, RS-Hg-SR. LC-MS analysis of this mercurial adduct detected a negative ion fragment of 782 m/z which on further ionization gave a ladder like pattern showing loss of mass units of 58 in each rung. This would seem to suggest the presence of a repeat polymer like structure containing 5 monomers, which, plus the thiol atom, gives a possible formula weight of 322;probably revealing only a part of the unknown Conthiol molecule whose properties and formula weight do not correlate with any known cellular thiol. Further analysis of the thiol released from the adduct on the Thiopropyl Sepharose 6B column by Infra-red (FTIR) provided little information except to confirm the presence of the thiol group and C=O stretch bands together with the possibility of a lactam ring at 1651 and 1634 cm·s-1.

Diagnostic strategies and the incidence of prostate cancer： reasons for the low reported incidence of prostate cancer in China

We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Research on Cancer （IARC）, the age-standardized incidence of prostate cancer in China is 1.6/105 person years （PY）, with a mortality rate of 1.0/105 PY and mortality-to-incidence rate ratio （MR/IR） = 0.63. The MR/IR ratio of prostate cancer in China was found to be higher than the average in Asia （MR/IR = 0.57） and much higher than that in North America （MR/IR = 0.13）. These data indicate that in China most prostate cancers were in the advanced stages at the time of diagnosis, and that patients had a short survival time thereafter. In 2004, Stamey et al. reported a retrospective American study of prostate cancer for the years 1983-2003. It was shown that most cases of prostate cancer detected by prostate-specific antigen （PSA） screening were in the advanced stage at the start of this 20-year period. These early follow-up data are quite similar to the results obtained from mass PSA screening of elderly men in Changchun, China. However, after the American programmes for early diagnosis and treatment of prostate cancer were accepted, tumours were diagnosed at earlier stages. On the basis of these findings, mass screening should be performed in the whole of China using serum PSA to facilitate early diagnosis and treatment of prostate cancer.

A longitudinal study of PSA and its influential factors in a cohort of Chinese men with initial PSA levels less than 4 ng ml-1

To evaluate the longitudinal change in prostate-specific antigen （PSA） and the influence of initial PSA on the PSA change. We retrospectively analysed health examination data collected at Beijing Hospital from March 2007 to November 2011. Men with an initial PSA levels less than 4 ng ml- 1 and an annual PSA test for 5 years were enrolled into the study. The men were separated into four groups by the initial PSA level （0-0.99, 1-1.99, 2-2.99 and 3-3.99 ng ml- 1）, and the difference in PSA change among the four groups was analysed. A total of 1330 men were enrolled into the study. The mean age, initial PSA and PSA velocity （PSAV） were 58.17± 14.63 （range 24-91） years, 1.18±0.79 （range 0-4） ng m1-1 and 0.04±0.25 （range -1.34±2.02） ng m1-1 year-1, Pearson＇s correlation analysis showed no correlation between initial PSA and PSAV （r=-0.036, P=0. 189）. The PSAV of the 0-0.99, 1-1.99, 2-2.99 and 3-3.99 ng m1-1 initial PSA groups was 0.03±0.11, 0.07±0.32, 0.03±0.34 and -0.01±0.43 ng m1-1 year-1, respectively （P=0.06）. As the initial PSA increased, the percentage of having a PSAV over 0.75 ng m1-1 year-1 and a negative PSAV both significantly increased. Males with a baseline PSA of 0-0.99, 1-1.99, 2-2.99 and 3-3.99 ng ml- 1 had a 1.88%, 6.16%, 16.30% and 57.81% chance, respectively, that their PSA would increase above 4.0 ng ml- 1 over the following 4 years （P〈0.0001）. The PSAV has no correlation with the initial PSA level. However, as the initial PSA increases, the chance that males will have an abnormal PSA or PSAV in the future increases.