Efficacy and safety of radiofrequency ablation for primary and secondary hyperparathyroidism with or without previous parathyroidectomy: a retrospective study.

INTRODUCTION: This study aimed to investigate and compare the therapeutic efficacy and safety of ultrasound-guided radiofrequency ablation (RFA), between primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT) patients, with or without previous parathyroidectomy (PTX). SUBJECTS AND METHODS: A total of 21 patients (7 PHPT, 14 SHPT) underwent RFA for hyperparathyroidism (HPT) at Kaohsiung Chang Gung Memorial Hospital, Taiwan. Five of the 14 SHPT patients had previously received PTX. The laboratory data, volume change of each parathyroid nodule, symptomatic scores, and complications were analyzed and compared between all groups at 1 and 7 days, and at 1, 3, 6, and 12 months after RFA. RESULTS: After RFA, the volume reduction ratio (VRR) for all patients at the last follow-up was 93.76%, and clinical symptoms significantly improved. At 12 months, all PHPT patients achieved successful treatment of intact PTH (iPTH). In SHPT patients, the mean iPTH value significantly decreased 1-day post-RFA, subsequently exhibiting a transient rebound which proceeded to decrease, with 57.1% reaching successful treatment standards. SHPT patients with PTX showed a lower complication score, shorter ablation time, higher iPTH baseline and outcomes, and lower VRR, compared to patients without PTX. The serum calcium level significantly decreased to normal range in 85.7% of all patients at 12 months. Severe hypocalcemia occurred in 23.8% at 1 week, and all were corrected with calcium supplements. CONCLUSIONS: RFA demonstrates a therapeutic efficacy similar to PTX. It can thus be considered an effective alternative treatment for PHPT, SHPT, or post-PTX patients who are unsuitable for another PTX.

Xenogeneic cell therapy provides a novel potential therapeutic option for cancers by restoring tissue function, repairing cancer wound and reviving anti-tumor immune responses.

Conventional cancer treatments such as surgery, radiotherapy, chemotherapy and targeted therapy, not only destruct tumors, but also injure the normal tissues, resulting in limited efficacy. Recent advances in cancer therapy have aimed at changing the host milieu of cancer against its development and progression by targeting tumor microenvironment and host immune system to eradicate tumors. To the host body, tumors arise in tissues. They impair the normal healthy tissue physiological function, become chronically inflamed and develop non-healing or overhealing wounds as well as drive immuno-suppressive activity to escape immunity attack. Therefore, the rational therapeutic strategies for cancers should treat both the tumors and the host body for the best efficacy to turn the deadly malignant disease to a manageable one. Xenogeneic cell therapy (i.e. cellular xenotransplantation) using cells from non-human source animals such as pigs has shown promising results in animal studies and clinical xenotransplantation in restoring lost tissue physiological function and repairing the wound. However, the major hurdle of xenogeneic cell therapy is the host immunological barriers that are induced by transplanted xenogeneic cells to reject xenografts. Possibly, the immunological barriers of xenogeneic cells could be used as immunological boosters to activate the host immune system. Here, we hypothesized that because of the biological properties of xenogeneic cells to the recipient humans, the transplantation of xenogeneic cells (i.e. cellular xenotransplantation) into cancer patients' organs of the same origin with developed tumors may restore the impaired function of organs, repair the wound, reduce chronic inflammation and revive the anti-tumor immunity to achieve beneficial outcome for patients.

The anti-tumor effect of intravesical administration of normal urothelial cells on bladder cancer.

BACKGROUND AIMS: Urothelial bladder cancer (UBC) is the second most common cancer of the genitourinary tract and for advanced forms of the disease it has a high mortality rate. There are no approved new molecularly targeted agents or chemotherapeutics for advanced UBC beyond cisplatin-based chemotherapy except the recently approved anti-programmed death ligand 1 (anti-PD-1/PD-L1) antibody. With complex genetic and epigenetic alterations in tumors, despite several druggable targets identified, to cure UBC is still a challenging unmet medical need. Like other cancers, UBC to the host body is considered as a wound, aging stem cell disease and immunosuppressive disorder. Therefore, we proposed a novel cellular approach to target the host body by intravesical instilling of normal urothelial cells that could repair the injury and reduce inflammation by activating body-reparative capacity and because non-self cells are transplanted, host body immune responses could be induced in the tumor microenvironment of UBC to restrain and even eliminate tumor cells. METHODS: In this study, we isolated and expanded normal male murine urothelial cells and intravesically administered them into the bladders of female mice of two orthotopic bladder tumor models and one urothelial injury model. RESULTS: We showed that the instillation of normal urothelial cells containing stem/progenitor cell population into bladders could have anti-tumor effect in orthotopic tumor models, possibly by activating immune responses and helping injured urothelium tissue recovery in a chemically induced urothelial injury model. CONCLUSIONS: Our findings could lead to an innovative and revolutionary cell therapy modality with normal urothelial cells as an effective and safe therapeutic option for UBC.

CCL2 increases αvß3 integrin expression and subsequently promotes prostate cancer migration.

BACKGROUND: Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family which is associated with the disease status and outcomes of cancers. Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. However, the effect of CCL2 on human prostate cancer cells is largely unknown. The aim of this study was to examine the role of CCL2 in integrin expression and migratory activity in prostate cancers. METHODS: Prostate cancer migration was examined using Transwell, wound healing, and invasion assay. The PKCδ and c-Src phosphorylations were examined by using western blotting. The qPCR was used to examine the mRNA expression of integrins. A transient transfection protocol was used to examine AP-1 activity. RESULTS: Stimulation of prostate cancer cell lines (PC3, DU145, and LNCaP) induced migration and expression of integrin αvß3. Treatment of cells with αvß3 antibody or siRNA abolished CCL2-increased cell migration. CCL2-increased migration and integrin expression were diminished by CCR2 but not by CCR4 inhibitors, suggesting that the CCR2 receptor is involved in CCL2-promoted prostate cancer migration. CCL2 activated a signal transduction pathway that includes PKCδ, c-Src, and AP-1. Reagents that inhibit specific components of this pathway each diminished the ability of CCL2 to effect cell migration and integrin expression. CONCLUSIONS: Interaction between CCL2 and CCR2 enhances migration of prostate cancer cells through an increase in αvß3 integrin production. GENERAL SIGNIFICANCE: CCL2 is a critical factor of prostate cancer metastasis.

Anabolic androgens affect the competitive interactions in cell migration and adhesion between normal mouse urothelial cells and urothelial carcinoma cells.

The urothelium is constantly rebuilt by normal urothelial cells to regenerate damaged tissues caused by stimuli in urine. However, the urothelial carcinoma cells expand the territory by aberrant growth of tumor cells, which migrate and occupy the damaged tissues to spread outside and disrupt the normal cells and organized tissues and form a tumor. Therefore, the interaction between normal urothelial cells and urothelial carcinoma cells affect the initiation and progression of urothelial tumors if normal urothelial cells fail to migrate and adhere to the damages sites to regenerate the tissues. Here, comparing normal murine urothelial cells with murine urothelial carcinoma cells (MBT-2), we found that normal cells had less migration ability than carcinoma cells. And in our co-culture system we found that carcinoma cells had propensity migrating toward normal urothelial cells and carcinoma cells had more advantages to adhere than normal cells. To reverse this condition, we used anabolic androgen, dihyrotestosterone (DHT) to treat normal cells and found that DHT treatment increased the migration ability of normal urothelial cells toward carcinoma cells and the adhesion capacity in competition with carcinoma cells. This study provides the base of a novel therapeutic approach by using anabolic hormone-enforced normal urothelial cells to regenerate the damage urothelium and defend against the occupancy of carcinoma cells to thwart cancer development and recurrence.

All-optical self-referencing measurement of vectorial optical arbitrary waveform.

We propose the Vectorial E-field Characterization Through all-Optical and self-Referenced (VECTOR) method to characterize vectorial optical arbitrary waveform with up to 100% duty cycle, which is free of ambiguity, iteration, radio-frequency or external optical reference, restriction on repetition rate, and requirement of external interferometric stabilization. The feasibility of VECTOR is experimentally verified by different waveforms created by a phase-modulated CW comb source and a built-in polarization line-by-line pulse shaper.

Self-referenced frequency comb measurement by using a polarization line-by-line pulse shaper.

A polarization line-by-line pulse shaper is used for generation and noniterative spectral phase retrieval of optical arbitrary waveforms (OAWs) spanning over the entire repetition period. The method is completely reference-free, making it particularly attractive in measuring high repetition-rate OAW.

Spontaneous ureteral rupture and review of the literature.

INTRODUCTION: Spontaneous ureteral rupture is defined as non-traumatic urinary leakage from the ureter. This is a diagnosis that, although uncommon, is important for emergency physicians to know about. The literature is relatively sparse. MATERIALS AND METHODS: This was a retrospective review of patients who were diagnosed with spontaneous ureteral rupture. From 2006 to 2012, 18 patients were diagnosed by radiography (computed tomography or intravenous urogram) with spontaneous ureteral rupture. These cases all showed extravasation of the contrast outside the excretory system. We evaluated underlying causes, diagnostic and therapeutic procedures, and outcomes. RESULTS: There were 9 men and 9 women with a median age of 59 years (range, 22-82 years). In 56% of patients, a ureteral stone was the cause; in 17% of, a ureteral stricture; in 1 patient, a ureteral tumor; and in the remaining 22%, no cause was identified. In 13 patients (72.2%), primary ureteroscopy to place D-J stents was performed. The average duration of ureteral catheter stenting was 21 days (range, 8-45 days). The other 5 patients (27.8%) were managed conservatively with antibiotic treatment and the outcome was good. CONCLUSIONS: Ureteral stones most commonly cause spontaneous ureteral rupture. In our experience, most patients received ureteroscopy and Double-J stenting. Conservative management with antibiotics also had good outcomes. Most patients had sudden onset of abdominal or flank pain. Spontaneous ureteral rupture should be kept in the differential diagnosis of patients with acute abdominal or flank pain in the emergency department.

Potential therapeutic roles of tanshinone IIA in human bladder cancer cells.

Tanshinone IIA (Tan-IIA), one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae, has been found to exhibit anticancer activity in various cancer cells. We have demonstrated that Tan-IIA induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. Here we explored the anticancer effect of Tan-IIA in human bladder cancer cell lines. Our results showed that Tan-IIA caused bladder cancer cell death in a time- and dose-dependent manner. Tan-IIA induced apoptosis through the mitochondria-dependent pathway in these bladder cancer cells. Tan-IIA also suppressed the migration of bladder cancer cells as revealed by the wound healing and transwell assays. Finally, combination therapy of Tan-IIA with a lower dose of cisplatin successfully killed bladder cancer cells, suggesting that Tan-IIA can serve as a potential anti-cancer agent in bladder cancer.

Noniterative data inversion of phase retrieval by omega oscillating filtering for optical arbitrary waveform measurement.

We propose a noniterative data inversion process for the phase retrieval by omega oscillating filtering method that could measure both isolated attosecond pulses and periodic optical arbitrary waveform (OAW). The built-in phase modulation depth recovery not only prevents the need of independent calibration (a critical advantage in the extreme ultraviolet regime) but provides a self-consistency check for the data integrity. Our experiments successfully retrieved OAW with ~100% duty cycle in the near infrared regime.

D-pinitol inhibits prostate cancer metastasis through inhibition of αVß3 integrin by modulating FAK, c-Src and NF-κB pathways.

Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. D-pinitol, a 3-methoxy analogue of d-chiro-inositol, was identified as an active principle in soy foods and legumes, and it has been proven to induce tumor apoptosis and metastasis of cancer cells. In this study, we investigated the anti-metastasis effects of D-pinitol in human prostate cancer cells. We found that D-pinitol reduced the migration and the invasion of prostate cancer cells (PC3 and DU145) at noncytotoxic concentrations. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. Treatment of prostate cancer cells with D-pinitol reduced mRNA and cell surface expression of αvß3 integrin. In addition, D-pinitol exerted its inhibitory effects by reducing focal adhesion kinase (FAK) phosphorylation, c-Src kinase activity and NF-kB activation. Thus, D-pinitol may be a novel anti-metastasis agent for the treatment of prostate cancer metastasis.

Portal Dynamics After Living Donor Liver Transplant in Pediatric Recipients: A 10-Year Follow-Up Retrospective Study.

BACKGROUND: It may be difficult for pediatric patients to evaluate the impact of liver transplantation (LT) on splenomegaly due to the natural growth course. The long-term dynamics of portal vein (PV) size and PV flow after LT in pediatric patients are unclear. We aimed to evaluate the long-term transition of the splenic size, PV size, and PV flow velocity in pediatric patients who underwent successful living donor liver transplantation (LDLT) and survived >10 years. METHODS: From October 2004 to December 2010, 39 pediatric patients (25 boys; 14 girls) underwent LDLT, received pre-LDLT and post-LDLT computed tomography scans and long-term ultrasound sonography follow-up, and survived >10 years without additional intervention at our institution. We analyzed the short- to mid-term and long-term impact of LDLT on splenic size, PV size, and PV flow velocity over time. RESULTS: The PV diameter increased throughout the 10-year follow-up (P < .001). The PV flow velocity increased 1 day after LDLT (P< .001); proceeded to decrease 3 days after LDLT, reaching a low point 6 to 9 months after LDLT; and remained stable throughout the 10-year follow-up. Regression of the splenic volume at 6 to 9 months after LDLT (P < .001) was noted. However, the splenic size steadily increased on long-term follow-up. CONCLUSIONS: Although LDLT has a significant short-term reduction effect on splenomegaly, the long-term transitional trend of the splenic size and PV diameter may increase along with children's growth. The PV flow reached a stable status 6 to 9 months after LDLT and remained so until 10 years after LDLT.

Ethnic differences in the age-related distribution of serum prostate-specific antigen values: A study in a Taiwanese male population.

This study investigates age-specific prostate-specific antigen (PSA) distributions in Taiwanese men and recommends reference ranges for this population after comparison with other studies. From January 1999 to December 2016, a total of 213,986 Taiwanese men aged above 19 years old without history of prostate cancer, urinary tract infection, or prostate infection were recruited from the Taiwan MJ cohort, an ongoing prospective cohort of health examinations conducted by the MJ Health Screening Center in Taiwan. Participants were divided into seven age groups. Simple descriptive statistical analyses were carried out and quartiles and 95th percentiles were calculated for each group as reference ranges for serum PSA in screening for prostate cancer in Taiwanese men. Serum PSA concentration correlated with age (r = 0.274, p<0.001). The median serum PSA concentration (5th to 95th percentile) ranged from 0.7 ng/ml (0.3 to 1.8) for men 20-29 years old (n = 6,382) to 1.6 ng/ml (0.4 to 8.4) for men over 79 years old (n = 504). The age-specific PSA reference ranges are as follows: 20-29 years, 1.80 ng/ml; 30-39 years, 1.80 ng/ml; 40-49 years, 2.0 ng/ml; 50-59 years, 3.20 ng/ml; 60-69 years, 5.60 ng/ml; 70-79 years, 7.40 ng/ml; over 80 years, 8.40 ng/ml. Almost no change occurred in the median serum PSA value in men 50 years old or younger, while a gradual increase was observed in men over 50. Taiwanese men aged 60 years above showed higher 95th percentile serum PSA values compared to Caucasian men and men in other Asian countries but were closer to those of Asian American and African American men. Results indicate significantly different PSA levels correlating to different ethnicities, suggesting that Oesterling's age-specific PSA reference ranges might not be appropriate for Taiwanese men. Our results should be further studied to validate the age-specific PSA reference ranges for Taiwanese men presented in this study.

Localization Strategy Prior to Radiofrequency Ablation for Primary and Secondary Hyperparathyroidism.

OBJECTIVE: Preoperative localization in patients with primary or secondary hyperparathyroidism before radiofrequency ablation (RFA) is crucial. There is currently a lack of consensus regarding imaging protocol. Evaluating the diagnostic performance of ultrasound, four-dimensional computed tomography (4D-CT), and technetium 99m-sestamibi single-photon-emission-computed tomography/computed tomography (SPECT/CT) is necessary for RFA of hyperparathyroidism. METHODS: This retrospective study recruited patients with primary or secondary hyperparathyroidism who underwent ultrasound, 4D-CT, and SPECT/CT before RFA at a single institution. The sensitivity, accuracy, and receiver operating characteristic curve analysis were used to evaluate the diagnostic performance of the imaging modalities. RESULTS: A total of 33 patients underwent RFA for hyperparathyroidism (8 patients with primary hyperparathyroidism, 25 patients with secondary hyperparathyroidism). Ultrasound had the highest sensitivity (0.953) and accuracy (0.943), while 4D-CT had higher sensitivity and accuracy than SPECT/CT (sensitivity/accuracy, 4D-CT vs. SPECT/CT: 0.929/0.920 vs. 0.741/0.716). Combined ultrasound with 4D-CT and the three combined modalities achieved equivalent, and the highest, diagnostic performance (sensitivity 1.000, accuracy 0.989). The lesion length and volume were important predictors of the diagnostic performance of 4D-CT and SPECT/CT (area under curve of length in 4D-CT/volume in 4D-CT/length in SPECT/volume in SPECT: 0.895/0.834/0.767/0.761). CONCLUSION: Combined ultrasound with 4D-CT provides optimal preoperative localization prior to RFA in patients with primary or secondary hyperparathyroidism. The length and volume of parathyroid lesions are determinative of the diagnostic performance of 4D-CT and SPECT/CT.

Polarization line-by-line pulse shaping for the implementation of vectorial temporal Talbot effect.

Vectorial optical arbitrary waveform generation is experimentally demonstrated by applying polarization line-by-line pulse shaping on a phase-modulated continuous laser frequency comb. Polarization shaped optical waveforms extending a 50-ps time window are successfully synthesized. Temporal Talbot effect is extended into the vectorial regime, where the distinct periodic temporal phases of the two orthogonally polarized pulse trains are exploited. In one example, we generate repetition-rate doubled circularly polarized pulses with alternating pulse-by-pulse handedness. In another example, complex instantaneous field polarizations are synthesized through the combination of line-by-line amplitude and temporal Talbot phase shaping. Our experimental results are measured through a dual-quadrature spectral interferometry system and are found in excellent agreements to the applied shaping controls.

Women urinate in the standing position do not increase post-void residual urine volumes.

AIMS: The effects of standing while voiding have seldom been investigated in women. We evaluate urodynamic parameters of voiding while standing in healthy women using uroflowmetry and post-void residual urine volume assessment. Results are compared with crouching and sitting. METHODS: Between July and October, 2008, a total of 30 healthy, nulliparous female volunteers were enrolled. Ages were 22-37 (mean: 28±4). Urodynamic studies were performed for all in sitting, crouching and standing positions; 3, 3 and 5 times in each position, respectively. Volunteers used homemade auxiliary appliances for collecting urine from the urethra and draining it forward when standing. Volume, maximum flow rate, mean flow rate and post-void residual urine volume were compared. RESULTS: Maximum and average flow rates in the sitting and standing positions were significantly different, but not between sitting and crouching or between crouching and standing. There were no differences in voided volume and post-void residual urine volume. There's no apparent learning curve for women in the standing position. CONCLUSIONS: Though flow rates are decreased while standing, post-void residual volume is not significantly different. Women have another choice for voiding in public restrooms.

Intravesical Administration of Xenogeneic Porcine Urothelial Cells Attenuates Cyclophosphamide-Induced Cystitis in Mice.

The urothelium of the bladder, renal pelvis, ureter and urethra is maintained through the regulated proliferation and differentiation of urothelial stem and progenitor cells. These cells provide a rich source of a novel urothelial cell therapy approach that could be used to protect, regenerate, repair and restore a damaged urothelium. Urothelial injury caused by physical, chemical and microbial stress is the pathological basis of cystitis (bladder inflammation). The loss of urothelial integrity triggers a series of inflammatory events, resulting in pain and hematuria such as hemorrhage cystitis and interstitial cystitis. Here we investigate a novel cell therapy strategy to treat cystitis by protecting the urothelium from detrimental stresses through intravesically instilling porcine urothelial cells (PUCs) into the bladder. Using a chemical-induced urothelial injury mouse model of cyclophosphamide (CPP)-induced hemorrhagic cystitis, we determined how the intravesical instillation of PUCs could protect the urothelium from toxic attack from CPP metabolites. We show that intravesical PUC instillation protected the bladder from toxic chemical attack in mice receiving CPP with reduced inflammation and edema. Compared with the vehicle control mice, the proliferative response to chemical injury and apoptotic cells within the bladder tissues were reduced by intravesical PUC treatment. Furthermore, the urothelium integrity was maintained in the intravesical PUC-treated group. After xenogeneic PUCs were introduced and adhered to the mouse urothelium, immunological rejection responses were observed with increased neutrophil infiltration in the lamina propria and higher immune-related gene expression. Our findings provide an innovative and promising intravesical PUC cell therapy for cystitis with urothelial injury by protecting the urothelium from noxious agents.

ASC-J9® increases the bladder cancer chemotherapy efficacy via altering the androgen receptor (AR) and NF-κB survival signals.

BACKGROUND: The current chemotherapy regimens may extend survival for patients with metastatic bladder cancer (BCa) for a few months, but eventually most patients succumb to disease because they develop resistance to their chemotherapy. METHODS: TCGA human clinical sample survey and urothelial tumor tissue microarrays (TMAs) were applied to investigate the expression of androgen receptor (AR) and NF-κB. Multiple BCa cell lines were used to test chemotherapy's efficacy via multiple assays including XTT, flow cytometry, TUNEL, and BrdU incorporation. The effects of the AR degradation enhancer, ASC-J9®, combined with various chemotherapy reagents were examined both in vivo and in vitro. RESULTS: We unexpectedly found that in muscle-invasive BCa (miBCa) the signals of both the AR and NF-κB were increased via a TCGA sample survey. Results from multiple approaches revealed that targeting these two increased signals by combining various chemotherapeutic agents, including Cisplatin, Doxorubicin or Mitomycin C, with ASC-J9® led to increase the therapeutic efficacy. The combined therapy increases the expression of the pro-apoptosis BAX gene and cell cycle inhibitor p21 gene, yet suppresses the expression of the pro-survival BCL2 gene in miBCa cells. Preclinical studies using an in vivo mouse model with xenografted miBCa cells confirmed in vitro cell line data showing that treatment with ASC-J9® combined with Cisplatin can result in suppressing miBCa progression better than Cisplatin alone. CONCLUSIONS: Together, these results support a novel therapeutic approach via combining Cisplatin with ASC-J9® to better suppress the progression of miBCa.

The Genomic Alterations of 5α-Reductases and Their Inhibitor Finasteride's Effect in Bladder Cancer.

BACKGROUND/AIM: Since androgens affect urothelial bladder cancer (UBC), we examined whether 5α-reductases (5-AR) have genomic alterations in UBC and whether 5α-reductase inhibitors (5-ARI) affect UBC. MATERIALS AND METHODS: The cBioPortal was used to analyze genomic alternations of 5-ARs in UBC cancer genomic datasets. Next, we used the Taiwan National Health Insurance Research database to conduct a population-based case-control study to investigate the effect of a 5-ARI, finasteride on UBC incidence. We also performed an XTT assay to examine the direct effect of finasteride on UBC cells. RESULTS: We found that 5-AR genomic alternations were observed in 29% of UBC patients and patients with alternations had shorter disease-free survival. Also, the use of finasteride with >180 cDDDs reduced the risk of UBC. Finasteride could directly inhibit UBC cell growth. CONCLUSION: Based on our findings, we concluded that 5-AR could be explored as a therapeutic target for UBC with 5-ARIs.

Androgen receptor facilitates the recruitment of macrophages in tumor microenvironment to promote upper urinary tract urothelial cell carcinoma progression.

Interactions between infiltrating macrophages in the tumor microenvironment (TME) and tumor cells contribute to tumor progression. The potential impacts of recruited macrophages to the upper urinary tract urothelial cell carcinomas (UUTUCs) progression remain unclear. Here we found human UUTUCs might recruit more macrophages than surrounding normal urothelial cells in human clinical specimens and in in vitro co-culture experiments with UUTUC cells and macrophages. The consequences of recruiting more macrophages to UUTUCs might then enhance UUTUC cell growth, migration and invasion. Further investigation found that the androgen receptor (AR) not only enhanced UUTUC cells capacity to recruit more macrophages, it could also promote the macrophages-enhanced UUTUC cells growth, migration and invasion. Downstream AR target cytokine search found AR might function through modulating CCL5 expression to influence UTTUC progression. Interruption of CCL5 partially reversed the AR-regulated macrophage-enhanced UUTUC progression. AR in UUTUC cells also increased tumor formation in vivo. Taken together, these results suggest that macrophages recruitment may enhance UUTUC progression, modulated by AR-CCL5 signal through alterations in chromatin state to establish a tumor microenvironment with recruited macrophages and cytokines to facilitate cell growth, migration and invasion.