Large-scale Prospective Validation Study of a Multiplex RNA Urine Test for Noninvasive Detection of Upper Tract Urothelial Carcinoma.

BACKGROUND: Current approaches for diagnosis and monitoring of upper tract urothelial carcinoma (UTUC) are often invasive, costly, and not efficient for early-stage and low-grade tumors. OBJECTIVE: To validate a noninvasive urine-based RNA test for accurate UTUC diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Urine samples were prospectively collected from 61 patients with UTUC and 99 controls without urothelial carcinomas, in five clinical centers between October 2022 and August 2023 prior to any invasive test (cystoscope or ureteroscope) or treatment. All samples were analyzed with a urine-based RNA test composed of eight genes (CA9, CCL18, ERBB2, IGF2, MMP12, PPP1R14D, SGK2, and SWINGN). The test results were presented with a risk score for each participant, which was applied to categorize patients into low- or high-risk groups. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The diagnosis of UTUC was based mainly on preoperative radiological examination criteria and confirmed by postoperative pathological results. The recursive feature elimination and support vector machine algorithms, χ2, and Student t test were used. RESULTS AND LIMITATIONS: The eight-gene urine test accurately detected UTUC patients and controls with an area under the curve (AUC) of 0.901 in a single-center testing cohort (n = 93) and an AUC of 0.926 in a multicenter clinical validation cohort (n = 66). In the merged validation cohort, the eight-gene urine test achieved high sensitivity of 90.16%, specificity of 88.89%, and overall accuracy of 89.38%. Remarkably, excellent performance was achieved in 11 low-grade UTUC patients with accuracy of 100%. However, this study collected the urine of UTUC patients only at a single preoperative time point and did not perform continuous tests during the pathological process of UTUC in the surveillance population. CONCLUSIONS: Our results demonstrated that the eight-gene urine test can differentiate accurately between UTUC and other urological diseases with high sensitivity and specificity. In clinical practice, it may be used for identifying UTUC patients effectively, leading to reduced reliance on ureteroscopy and blind surgery. PATIENT SUMMARY: In this study, we investigated a multiplex RNA urine test for noninvasive upper tract urothelial carcinoma (UTUC) diagnosis before treatment. We found that the risk scores derived from the multiplex RNA urine test differed significantly between UTUC patients and corresponding controls.

Circulating tumor cells in patients undergoing androgen deprivation therapy with versus without cryosurgery for metastatic prostate cancer: a retrospective analysis.

BACKGROUND: The study aimed to assess the value of circulating tumor cells (CTCs) as a prognostic and treatment response marker in patients undergoing androgen deprivation therapy (ADT) plus cryosurgery vs. ADT alone for metastatic prostate cancer (mPCA). METHODS: This retrospective analysis included 43 patients with mPCA: 23 receiving ADT alone (control) and 20 receiving additional cryosurgery (cryosurgery group). CTCs and progression-free survival (PFS) were compared between the two groups. Cox proportional hazards regression was conducted to identify variables associated with PFS. RESULTS: Median PFS was 35 months (IQR, 33­37) in the cryosurgery group vs. 30 months (IQR, 27­32) in the control (p < 0.001). CTCs count was significantly lower in the cryosurgery group at both 3 months (z = 2.170, p = 0.030) and 12 months (z = 2.481; p = 0.013). In comparison to the baseline, the number of CTCs at both 3 and 12 months was lower in the cryosurgery group (p = 0.004 and p < 0.001, respectively), but not in the ADT alone group. In multivariate Cox regression, shorter PFS was associated with baseline PSA ≧100 ng/ml (HR 6.584, 95% CI, 5.309­8.166), biopsy Gleason score ≧ 8 (HR 2.064, 95% CI, 1.608­2.650), clinic T stage>T2b (HR 5.021, 95% CI, 3.925­6.421), number of bone metastases>3 (HR 3.421, 95% CI, 2.786­4.202), positive CTCs at 3 months post-treatment (HR 6.833, 95% CI, 5.176­9.022), positive CTCs 1 year post-treatment (HR 6.051, 95% CI, 4.347­8.424). Prostate cryosurgery was associated with longer PFS (HR 0.062, 95% CI, 0.048­.080). CONCLUSIONS: CTC was a prognostic and treatment response marker for mPCA. ADT plus cryosurgery could reduce CTCs and prolong PFS vs. ADT alone in mPCA patients with low metastatic volume.

NANOG regulates the proliferation of PCSCs via the TGF-ß1/SMAD pathway.

PURPOSE: In prostate cancer, castration resistance is a factor that frequently leads to death in individuals with this disease. Recent studies have suggested that prostate cancer stem cells (PCSCs) are pivotal regulators in the establishment of castration resistance. The nanog homeobox (NANOG) and the transforming growth factor (TGF)-ß1/drosophila mothers against decapentaplegic protein (SMAD) signaling pathways are involved in several cancer stem cells but are not involved in PCSCs. The purpose of this study is to investigate the effect of NANOG on the proliferation of PCSCs regulated by the TGF-ß1/SMAD signaling pathway. METHODS: In this study, we used flow cytometry to isolate CD44+/CD133+/NANOG+ PCSCs from DU145 prostate cancer cells. Then we used short hairpin RNA to silence NANOG and observed the biological behavior and the TGF-ß1/SMAD signal of PCSCs. RESULTS: NANOG decreased PCSC proliferation, increased apoptosis, and blocked cell cycling at G0/G1. Furthermore, reduction in the TGF-ß1, p15, and p-SMAD2 expression was observed. CONCLUSION: These findings suggest that NANOG positively regulates the growth of PCSCs through the TGF-ß1/SMAD signaling pathway.

Cancer cell membrane-cloaked mesoporous silica nanoparticles with a pH-sensitive gatekeeper for cancer treatment.

Nanoparticular drug delivery system (NDDS) has great potential for enhancing the efficacy of traditional chemotherapeutic drugs. However, it is still a great challenge to fabricate a biocompatible NDDS with simple structure capable of optimizing therapeutic efficacy, such as high tumor accumulation, suitable drug release profile (e.g. no premature drug leakage in normal physiological conditions while having a rapid release in cancer cells), low immunogenicity, as well as good biocompatibility. In this work, a simple core/shell structured nanoparticle was fabricated for prostate cancer treatment, in which a mesoporous silica nanoparticle core was applied as a container to high-efficiently encapsulate drugs (doxorubicin, DOX), CaCO3 interlayer was designed to act as sheddable pH-sensitive gatekeepers for controlling drug release, and cancer cell membrane wrapped outlayer could improve the colloid stability and tumor accumulation capacity. In vitro cell experiments demonstrated that the as-prepared nanovehicles (denoted as DOX/MSN@CaCO3@CM) could be efficiently uptaken by LNCaP-AI prostate cancer cells and even exhibited a better anti-tumor efficiency than free DOX. In addition, Live/Dead cell detection and apoptosis experiment demonstrated that MSN/DOX@CaCO3@CM could effectively induce apoptosis-related death in prostate cancer cells. In vivo antitumor results demonstrated that DOX/MSN@CaCO3@CM administration could remarkably suppress the tumor growth. Compared with other tedious approaches to optimize the therapeutic efficacy, this study provides an effective drug targeting system only using naturally biomaterials for the treatment of prostate cancer, which might have great potential in clinic usage.

Is cryosurgery a feasible local therapy for bone metastatic prostate cancer?

INTRODUCTION: This study aims to assess whether cryosurgery is a feasible local therapy for bone metastatic prostate cancer (bmPCa). METHODS: A total of 23 patients with bmPCa who received cryosurgery and adjuvant androgen deprivation therapy (ADT) were included in the cryosurgery group (Group 1). Another 23 matched patients who received only ADT served as the control (Group 2). Prostate-specific antigen (PSA) nadir level, time to PSA nadir, time to castration-resistant prostate cancer (CRPC), progression-free survival and therapy response of bone metastases were compared between the groups. RESULTS: The median follow-up time in Group 1 and Group 2 patients was 37 (range 19-53) months and 42 (range 24-56) months, respectively. Patients in Group 1 had fewer local complications, lower PSA nadir level (0.23 ng/mL vs. 4.01 ng/mL; p = 0.024), shorter median time to PSA nadir (3 months vs. 7 months; p < 0.001), longer median time to CRPC (36 months vs. 27 months; p = 0.002) and longer progression-free survival (35 months vs. 26 months; p = 0.003) compared to those in Group 2. Therapy responses of bone metastases were similar in the two treatment groups (p = 0.689). CONCLUSION: Cryosurgery is a feasible local therapy for bmPCa patients with prostate volume less than 50 mL and without bulk tumours outside the prostate capsula. Cryosurgery may decrease PSA nadir level, local complications and time to PSA nadir, delay time to CRPC and improve progression-free survival.

Cytoreductive cryosurgery in patients with bone metastatic prostate cancer: A retrospective analysis.

The current study is a retrospective analysis of 49 patients with bone metastatic prostate cancer: 26 receiving androgen deprivation therapy (ADT) alone versus 23 receiving cytoreductive cryosurgery of the primary tumor plus ADT treatment. Progression-free survival (PFS) was the primary outcome variable, and Cox proportional hazards regression analysis was used to identify predictors for PFS. The baseline characteristics were generally comparable between the 2 groups. Median follow-up time was 41 months (range 24-56) and 37 months (range 19-53) in ADT alone group and cryosurgery groups, respectively. Patients receiving cryosurgery had significantly longer PFS (35 vs 25 months, P = 0.0027) and time to castration resistance (36 vs 25 months, P = 0.0011). Cox multivariate analysis associated longer PFS with the following factors: cryosurgery (HR0.207, 95% CI 0.094-0.456), lower prostate specific antigen at diagnosis (≤100 ng/ml, HR0.235, 95% CI 0.072-0.763) and lower Gleason score (≤7, HR0.195, 95% CI 0.077-0.496). Cryosurgery reduced the risk of progression by 79.3%. In conclusion, cytoreductive cryosurgery of the primary tumor in patients with bone metastatic prostate cancer could reduce the risk of progression and delay time to castration-resistant prostate cancer.

The Comparison of Urinary Stones Between She Minority and Han Nationality in East Fujian, China.

BACKGROUND: The purpose of the study was to compare the incidence of urinary stones of She minority and Han nationality and analyze the composition of urinary stones. METHODS: The study was performed in 381 cases with 181 She minority and 200 Han nationality. The composition of stones was mainly analyzed by infrared absorption spectrum. The incidence of urinary stones at different ages, different gender and different parts was compared between She minority and Han nationality. RESULTS: The urinary stone incidence of males was about twice as high as in women in She minority and Han nationality, and the incidence reached its maximum between the ages of 41 and 60, but the incidence decreased after 60 years of age. The distribution characteristics of urethra stones between She minority and Han nationality showed a significant difference (p < 0.05). The differences of carbonate apatite and struvite in male and female were statistically significant between She minority and Han nationality (p < 0.05). The level of Ca2+ and HPO42- in serum showed significant difference between She minority and Han nationality (p < 0.05). CONCLUSIONS: According to these results, we put forward corresponding preventive measures of urinary stones in She minority.

Amygdalin inhibits renal fibrosis in chronic kidney disease.

Renal interstitial fibrosis is a common outcome of chronic renal diseases. Amygdalin is one of a number of nitrilosides, the natural cyanide­containing substances abundant in the seeds of plants of the prunasin family that are used to treat cancer and relieve pain. However, whether amygdalin inhibits the progression of renal fibrosis or not remains unknown. The present study aimed to assess the therapeutic potential of amygdalin by investigating its effect and potential mechanism on the activation of renal interstitial fibroblast cells and renal fibrosis in rat unilateral ureteral obstruction (UUO). Treatment of the cultured renal interstitial fibroblasts with amygdalin inhibited their proliferation and the production of transforming growth factor (TGF)­ß1. In the rat model of obstructive nephropathy, following ureteral obstruction, the administration of amygdalin immediately eliminated the extracellular matrix accumulation and alleviated the renal injury on the 21st day. Collectively, amygdalin attenuated kidney fibroblast (KFB) activation and rat renal interstitial fibrosis. These results indicate that amygdalin is a potent antifibrotic agent that may have therapeutic potential for patients with fibrotic kidney diseases.