The Role of Cysteine Cathepsins in Cancer Progression and Drug Resistance.

Cysteine cathepsins are lysosomal enzymes belonging to the papain family. Their expression is misregulated in a wide variety of tumors, and ample data prove their involvement in cancer progression, angiogenesis, metastasis, and in the occurrence of drug resistance. However, while their overexpression is usually associated with highly aggressive tumor phenotypes, their mechanistic role in cancer progression is still to be determined to develop new therapeutic strategies. In this review, we highlight the literature related to the role of the cysteine cathepsins in cancer biology, with particular emphasis on their input into tumor biology.

Identification of Clinically Significant Prostate Cancer by Combined PCA3 and AMACR mRNA Detection in Urine Samples.

PURPOSE: Preclinical evaluation of PCA3 and AMACR transcript simultaneous detection in urine to diagnose clinical significant prostate cancer (prostate cancer with Gleason score ≥7) in a Russian cohort. PATIENTS AND METHODS: We analyzed urine samples of patients with a total serum PSA ≥2 ng/mL: 31 men with prostate cancer scheduled for radical prostatectomy, 128 men scheduled for first diagnostic biopsy (prebiopsy cohort). PCA3, AMACR, PSA and GPI transcripts were detected by multiplex reverse transcription quantitative polymerase chain reaction, and the results were used for scores for calculation and statistical analysis. RESULTS: There was no significant difference between clinically significant and nonsignificant prostate cancer PCA3 scores. However, there was a significant difference in the AMACR score (patients scheduled for radical prostatectomy p=0.0088, prebiopsy cohort p=0.029). We estimated AUCs, optimal cutoffs, sensitivities and specificities for PCa and csPCa detection in the prebiopsy cohort by tPSA, PCA3 score, PCPT Risk Calculator and classification models based on tPSA, PCA3 score and AMACR score. In the clinically significant prostate cancer ROC analysis, the PCA3 score AUC was 0.632 (95%CI: 0.511-0.752), the AMACR score AUC was 0.711 (95%CI: 0.617-0.806) and AUC of classification model based on the PCA3 score, the AMACR score and total PSA was 0.72 (95%CI: 0.58-0.83). In addition, the correlation of the AMACR score with the ratio of total RNA and RNA of prostate cells in urine was shown (tau=0.347, p=6.542e-09). Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use. CONCLUSION: The AMACR score is a good predictor of clinically significant prostate cancer. Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use. Evaluation of the AMACR score and classification models based on it for clinically significant prostate cancer detection with larger samples and a follow-up analysis is promising.

Near-infrared fluorescence with indocyanine green for diagnostics in urology: initial experience.

INTRODUCTION: Fluorescence imaging with indocyanine green is used in urology for the detection of sentinel lymph nodes and identification of prostate margins in radical prostatectomy for delineation of resection zone and selective clamping of vessels in partial nephrectomy; for identification and evaluation of length of ureteral strictures; for assessment of perfusion and viability of anastomoses during reconstructive stage of cystectomy. Safety of this technique is proven, while its diagnostic value and usefulness is still controversial. METHODS: This pilot study of using the SPY Elite Fluorescence Imaging System for diagnostics was performed in the I.M. Sechenov First Moscow State Medical University. Ten patients were enrolled: four patients underwent retropubic RP and lymph node dissection, five patients underwent partial nephrectomy, and one patient underwent ureteroplasty. Fluorophore was injected transrectally with TRUS guidance during RP in order to assess the lymph nodes. During partial nephrectomy, the compound was injected intravenously to differentiate the tumor from parenchyma by its blood supply. During ureteroplasty, the indocyanine green solution was injected into the renal pelvis to dye the ureter and locate the stricture. RESULTS: Sensitivity of this technique for visualization of sentinel lymph nodes was 100%, and specificity was 73.3%. In patients who underwent partial nephrectomy, all lesions were malignant and hypofluorescent when compared with healthy parenchyma. SPY allowed us to determine the location and extension of the stricture during ureteroplasty. No hypersensitivity reactions or complications were observed during injection of the compound.