99mTc‐(EDDA/tricine)‐HYNIC‐GnRH analogue as a potential imaging probe for diagnosis of prostate cancer
Arezou Masteri FarahaniFariba MalekiNourollah SadeghzadehSaeid AbediankenariSeyed Mohammad AbediMostafa Erfani
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Prostate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC-conjugated GnRH analogue and labeled it by 99m Tc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate 99m Tc-(tricine/EDDA)-HYNIC-Ahx-[DLys6 ]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN-CaP and DU-145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN-CaP were superior to DU-145 cells. The Kd values for LN-CaP and DU-145 cells were 41.91 ± 7.03 nM and 55.96 ± 10.56 nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of 99m Tc-HYNIC-Ahx-[DLys6 ]GnRH was 4.14 at 1 hr p.i. that decreased to 2.41 at 4 hr p.i. in LN-CaP tumor-xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor-mediated. The lesion was visualized clearly using 99m Tc-[DLys6 ]GnRH at 1 hr p.i. Accordingly, this research highlights the capability of 99m Tc-(tricine/EDDA)-HYNIC-Ahx-[DLys6 ]GnRH peptide as a promising agent for GnRHR-expressing tumor imaging.Keywords:
Tricine
[Objective] To establish a Tricine-SDS-PAGE method to separate and purify small peptides from Periplaneta americana.[Method] The effects of the Tricine-SDS-PAGE method with different proportions of three gels to separate the small peptides were compared,and the proper method for small peptides separation was established.[Result] The Marker could be separated by Tricine-SDS-PAGE to a certain extent,however,the samples assembled in the separation,spacer and stacking gels and could not been separated.[Conclusion] we should seek for the most appropriate Tricine-SDS-PAGE method or better methods for separating small pepetides.
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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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An efficient method for the separation of proteins in the mass range 1-100 kDa with minigel electrophoresis system was developed in the present study. Tricine (N-(2-Hydroxy-1,1-bis (hydroxymethyl) ethyl) glycine)-SDS-PAGE allows a resolution for proteins smaller than 30 kDa at lower acrylamide concentration than that in other electrophoretic methods. But reliable Tricine-SDS- PAGE protocols for minigel system remain to be established. In our study, Tricine-SDS-PAGEs were conducted with different composition of gels varied with concentration of acrylamide-bisacrylamide, urea, and glycerol, to develop optimized protocols of Tricine-SDS gels for minigel system. Our results indicated that gel composition containing 10% glycerol (w/v) and 4.2M urea could provide an ideal resolution for separation of small mass proteins. Then calibration curves for different types of separating gels demonstrated effective linear mobilities, and correlation coefficients of all gels were above 0.95, and the highest is the 10%T, 3%C gel, which reached 0.97. Results from the immunoblotting experiment of a 14-kDa mouse HMGA2 polypeptide also showed that the optimized protocols of minigel had excellent compatibility with Western Blot. In conclusion, the developed protocols of Tricine-SDS-PAGE for minigel provide a new choice for efficient, reproducible and convenient separation of low molecular weight proteins.
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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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Abstract Background We assessed the effect of biopsy location on the prostate cancer detection and clinically significant prostate cancer. Methods A total of 2774 patients with 12‐core prostate transrectal ultrasound‐guided prostate biopsy were included for per core analysis. Multivariate Cox regression analysis was performed to evaluate the effect of the location of biopsy on the prostate cancer and clinically significant prostate cancer detection. Results Prostate cancer was found in 775 patients (27.9%) and 576 prostate cancer patients (20.8%) were found to be clinically significant. The core length ( P = .043), tumor length ( P < .001), and % tumor length ( P < .001) were significantly different according to the biopsy location. The detection rates for prostate cancer and clinically significant prostate cancer differed significantly according to the location of biopsy. Multivariate analysis revealed that the apical core was significantly related with increased detection of prostate cancer and clinically significant prostate cancer. The lateral core, in addition to apical core, was found to be significantly related with increased detection rates of prostate cancer and clinically significant prostate cancer in men with prostate‐specific antigen <10 ng/mL. Conclusions More in‐depth discussions on the location of standard 12‐core prostate biopsy are considered necessary. Apical core and lateral core biopsies may be helpful, especially in patients with prostate‐specific antigen ˂10 ng/mL if additional biopsies are planned following findings of no target lesions on imaging studies.
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