The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients＇ sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points： point A, pre-treatment; point B, at the nadir of the prostate- specific antigen （PSA） level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients＇ sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I （ApoC-I）. Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-i protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.

Bone markers predict survival in castration-resistant prostate cancer patients treated with docetaxel

AIM: To investigate the relationship between clinicopathological features and bone turnover markers in castration-resistant prostate cancer(CRPC) patients treated with docetaxel.METHODS: Thirty-three patients were enrolled in this study. Serum levels of carboxyterminal cross-linked telopeptide of type 1 collagen generated by metalloproteinases(1CTP) and alkaline phosphatase(ALP) were measured at the start of docetaxel chemotherapy. We examined the relationship between clinicopathological features and serum levels of 1CTP and ALP levels in CRPC patients treated with docetaxel.RESULTS: For the total patient group, the mean ± standard deviation(SD) values for docetaxel chemotherapy dose, dose intensity, dosage interval, and num-ber of cycles were 59.3 ± 10.6 mg/m2, 13.9 ± 5.2 mg/m2 per week, 4.7 ± 1.2 wk, and 11.2 ± 7.4, respectively. Fourteen patients died from prostate cancer. Patients were divided into two groups according to mean + SD of serum 1CTP(8.2 ng/m L) and ALP(538.2 IU/L) levels at the start of docetaxel chemotherapy. Patients with lower levels of serum 1CTP and ALP had significantly better survivals than those with higher serum levels(P < 0.05).CONCLUSION: Serum levels of 1CTP and ALP are predictors of survival in patients with CRPC who are treated with docetaxel.

Worsening of the low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio in patients with prostate cancer after androgen deprivation therapy

Dear Editor, Prostate cancer （PCa） is the most frequently diagnosed male cancer in Western countries, and the number of PCa patients is also rapidly increasing in ]apan.1,2 Simultaneously, androgen deprivation therapy （ADT） has also been increasingly used in PCa patients in recent years2-5 However, the long-term use of ADT is associated with a variety of pivotal adverse events, including diabetes, anemia, osteoporosis, serum lipid profile changes, and cardiovascular disease （CVD）.1,2 Higher low-density lipoprotein cholesterol （LDL-C） and/or lower high-density lipoprotein cholesterol （HDL-C） are well-established risk factors for CVD, and control of their levels has been an important goal in the treatment and prevention of CVD.6,7 Recently, another alternative parameter, the LDL-C to HDL-C （L/H） ratio, has been reported to be strongly associated with CVD and is thought to be a better predictor of future CVD than LDL-C alone. Closely monitoring serum lipid profile, including the L/H ratio changes affected by ADT, is a key to preventing CVD in PCa patients. Moreover, we previously suggested that a higher L/H ratio might have an impact on the development of arterial stiffness after ADT administration,r Although some cutoff points of the L/H ratio have been reported in clinical use, it has been suggested that thrombosis can occur when the L/H ratio increases to around 2.5 or more in East Asian populations.6 The aim of the present study was to investigate the changes in serum lipid profile and to identify the clinical factors associated with an increased L/H ratio in PCa patients who received ADT.