Bladder cancer-associated nuclear matrix proteins.

The early diagnosis of bladder cancer is central to the effective treatment of the disease. Presently, there are no methods available to easily and specifically identify the presence of bladder cancer cells. The prevailing method for the detection of bladder cancer is the identification of bladder cancer cells by morphological examination of exfoliated cells or biopsy material by a pathologist. A hallmark of the malignant or transformed phenotype is an abnormal nuclear shape, the presence of multiple nucleoli, and altered patterns of chromatin organization. Nuclear structural alterations are so prevalent in cancer cells that they are commonly used as markers of transformation for many types of cancer. Nuclear shape is determined by the nuclear matrix, the dynamic skeleton of the nucleus. The nuclear matrix is the structural component of the nucleus that determines nuclear morphology, organizes the DNA in a three-dimensional fashion that is tissue specific, and has a central role in the regulation of a number of nuclear processes, including the regulation of DNA replication and gene expression. Previous investigations into prostate and breast cancer have revealed that nuclear matrix protein (NMP) composition undergoes alterations with transformation and that the nuclear matrix can serve as a marker for the malignant phenotype. In this study, we have identified NMPs with which it is possible to differentiate human bladder tumors from normal bladder epithelial cells. We examined the NMP composition of 17 matched tumor and normal samples from patients undergoing surgery for bladder cancer. We have identified six proteins present in all tumor samples that are not present in the corresponding normal samples and three proteins that are unique to the normal bladder tissues in comparison with the tumor samples. Five of the six bladder cancer-associated proteins were also identified in three human bladder cancer cells lines examined (253j, UMUC-2, and T24). Therefore, we have demonstrated that nuclear matrix composition is able to differentiate bladder cancer from normal bladder tissue and may provide useful tools for early detection and recurrence of the disease. Importantly, these markers may provide valuable tools for cytopathological screening for bladder carcinoma.

1,25-Dihydroxy-16-ene-23-yne-vitamin D3 and prostate cancer cell proliferation in vivo.

OBJECTIVES: 1,25-Dihydroxyvitamin D can inhibit the proliferation of prostate cancer cells, but its clinical use is limited by hypercalcemia. We examined the effects of a "noncalcemic" vitamin D analogue, 1,25-Dihydroxy-16-ene-23-yne-cholecalciferol (16-23-D3), on the proliferation of human prostate cancer cells in a mouse model. METHODS: Twenty-four athymic nude mice were inoculated with human prostate carcinoma cells from the PC-3 cell line. Twelve mice (experimental group) received injections of 1.6 micrograms of 16-23-D3 on alternate days over a 22-day period. Twelve mice (control group) received sham injections. Tumor volumes, pathologic findings, and terminal serum calcium levels were compared between groups. RESULTS: The relative increase in tumor volume was significantly lower in the experimental than in the control group in the first interval following treatment (P < 0.01). Mean tumor volumes in the experimental group were approximately 15% smaller than in the control group. Serum calcium levels did not differ between groups. CONCLUSIONS: 16-23-D3 showed modest antiproliferative effects on prostate cancer cells in this model without evidence of drug-induced hypercalcemia. These findings support the concept that vitamin D analogues can inhibit the proliferation of human prostate cancer cells in vivo.

Human prostate cancer cells: inhibition of proliferation by vitamin D analogs.

1,25-Dihydroxyvitamin D [1,25(OH)2D3, calcitriol] can inhibit the proliferation of some human prostate cancer cells but its clinical use is limited by hypercalcemia. We therefore explored the bioactivity of less calcemic vitamin D analogs. We studied the effects of calcitriol and 3 synthetic analogs at concentrations of 10(-6) to 10(-12) M on the in vitro proliferation of 3 human prostate carcinoma cell lines: DU 145, PC-3, and LNCaP. Calcitriol and analogs showed significant antiproliferative activity on PC-3 and LNCaP cells. DU 145 cells were inhibited by the analogs only. We conclude that vitamin D analogs warrant further investigation as therapeutic agents in prostate cancer.