870 CEACAM1 EXPRESSION DISTINGUISHES INDOLENT FROM LETHAL PROSTATE CANCER
Derya TilkiMaria A. SvenssonShahrokh F. ShariatB.B. SingerOliver ReichChristian G. StiefOve AndrénSwen-Olov AnderssonJonas JohanssonFrancesca DemichelisMark A. RubinSefa ErgünSaeed Rafii
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Expression (computer science)
We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.
Prostate biopsy
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Prostate cancer is a malignancy commonly occuring in male genitourinary system.Androgen receptor promotes gene transcription in prostate cell growth and carcinogenesis of prostate cancer,which makes it to become an important target in prostate cancer treatment possibly.Prostate cancer may be deteriorated into be castration-resistant prostate cancer easily after androgen deprivation therapy,so it is popular to seek the effective androgen receptor antagonists for treating of castration-resistant prostate cancer.This review focuses on the action mechanism and the development of androgen receptor antagonists for the treatment of prostate cancer.
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Circulating tumor cell
Localized disease
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Androgen deprivation therapy has been the standard treatment for the patients with advanced prostate cancer. Androgen deprivation therapy initially suppresses the growth of prostate cancer. However, most patients eventually progress to castration-resistant prostate cancer. Novel drugs, including enzalutamide and abiraterone acetate, are recently able to be used for the patients with castration-resistant prostate cancer. Even so, the therapeutic options for castration-resistant prostate cancer are not enough. Interestingly, androgen receptor degradation enhancer ASC-J9 is reported to degrade the androgen receptor, resulting in the suppression of the growth in castration-resistant prostate cancer cells. In this chapter, ASC-J9 for prostate cancer is reviewed.
Enzalutamide
Abiraterone acetate
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Prostate cancer is one of the most common and socially significant cancers among men. The aim of this study was to identify significant changes in the expression of exosomal miRNAs associated with an increase in the level of prostate specific antigen in castration-resistant prostate cancer during therapy and to evaluate them as potential prognostic markers for this category of disease. High-throughput miRNA sequencing was performed on 49 blood plasma samples taken from 11 Russian patients with castration-resistant cancer during therapy. Bioinformatic analysis of the obtained miRNA-seq data was carried out. Additionally, miRNA-seq data from the PRJNA562276 project were analyzed to identify exosomal miRNAs associated with castration-resistant prostate cancer. We found 34 differentially expressed miRNAs associated with the progression of castration-resistant prostate cancer during therapy in Russian patients. It was also shown that hsa-miRNA-148a-3p expression can serve as a potential prognostic marker. We found the exosomal miRNA expression signature associated with castration-resistant prostate cancer progression, in particular on the Russian patient cohort. Many of these miRNAs are well-known players in either oncogenic transformation or tumor suppression. Further experimental studies with extended sampling are required to validate these results.
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Abstract : Prostate cancer cells have a remarkable affinity to develop metastases in bone. Clinical data and laboratory observations both suggest that bone-malignant epithelium interactions play a central role in prostate cancer progression. We have developed an in vitro model system that reflects the most common cellular features of prostate cancer bone metastases. The model consists of the prostate cancer cell lines: MDA PCa 2a or MDA PCa 2b (the TabBO cells) co-cultured with primary mouse osteoblasts (PMO). The two cell types share medium but are not in physical contact because the prostate cancer cells are plated in cell-culture inserts. We have established the optimal conditions for growing prostate cancer cells in co-culture with PMO. Using those conditions, we defined the effect that prostate cancer cells have in PMO in our model system. This effect reflects the interaction between prostate cancer cells and osteoblasts in prostate cancer bone metastases. Therefore we conclude that our model system may be suitable to study the molecular and cellular events involved in the new bone formation observed in prostate cancer bone metastases.
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To evaluate the spatial distribution of prostate cancer detected at a single positive biopsy (PBx) and a repeat PBx (rPBx).We evaluated 533 consecutive men diagnosed with prostate cancer who underwent radical prostatectomy using a clinical map document based on XML (cMDX©)-based map model of the prostate. We determined the number of cancer foci, relative tumour volume, Gleason score, zone of origin, localisation, and pathological stage after stratification according to the number of PBx sessions (PBx vs rPBx). The distribution of 3966 prostate cancer foci was analysed and visualised on heat maps. The colour gradient of the heat map was reduced to six colours representing the frequency classification of prostate cancer using an image posterisation effect. Additionally, the spatial distribution of organ-confined prostate cancer between PBx and rPBx was evaluated.Prostate cancer diagnosed on PBx was mostly localised to the apical portion and the peripheral zone of the prostate. Prostate cancer diagnosed on rPBx was more frequently found in the anterior portion and the base of the prostate. Organ-confined prostate cancer foci were mostly localised in the dorsolateral zone of the prostate in men at PBx, whereas men at rPBx had more prostate cancer foci in the anterior portion.The spatial distribution of prostate cancer with rPBx differs significantly from the spatial distribution of prostate cancer with PBx. The whole anterior portion of the prostate should be considered by rPBx.
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Objective To investigate the expressions of mitosis regulative factor STK-15 in prostate cancer and the relationship between STK-15 and the biological behavior of prostate cancer.Methods The expressions of STK-15 were examined by using immunohistochemical staining on 63 cases of prostate cancer and 16 cases of normal prostate tissues.And the expressions of STK-15 mRNA were detected by using RT-PCR in 14 cases of prostate cancer,BPH,and normal prostate tissues respectively.Results The STK15 protein was expressed in 98%(62/63) of prostate cancer tissue and in 19%(3/16) of normal prostate tissues.The difference between these expression rates was significant(P0.001).Meanwhile,the positive expression rates of STK-15 mRNA in prostate cancer,BPH,and normal prostate tissue were 93%(13/14),21%(3/14) and 14%(2/14) respectively.Compared with those in BPH and normal prostate tissue,the STK-15 mRNA expression rate in prostate cancer was significantly high(P0.001).Meanwhile,there was no significant difference between those in BPH and normal prostate tissue(P0.05).Conclusion The expressions of STK-15 increase in prostate cancer tissues which may contribute to the prostate carcinogenesis.
Prostate Diseases
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