[Research progress on the role of type II innate lymphoid cells in liver diseases].

Type II innate lymphoid cell (ILC2) is a newly identified innate immunological cell that belongs to the lymphocyte lineage in cell morphology, resides in the body's mucosal tissues, and has the dual functions of innate and adaptive immunity to promote tissue remodeling and repair after injury. Additionally, it is involved in the occurrence and development of a variety of liver diseases and plays an important role in maintaining the immunological homeostasis of the liver region. This article reviews the differentiation, development, and biological functions of ILC2, with particular attention to the research progress in liver diseases.

[Trend analysis of influenza vaccination among hospitalized elderly people in Beijing, 2013-2019].

OBJECTIVE: To analyze the influenza vaccination trend of hospitalized elderly people (≥ 60 years old) in Beijing from 2013 to 2019. METHODS: The influenza vaccination status and hospitalization information of elderly people were extracted from the Beijing Elderly Influenza Vaccination database (2013-2019) and the Beijing Urban Employee Basic Medical Insurance database (2013-2019), se-parately. The influenza vaccine coverage rates and annual percentage change were calculated to compare the vaccination trends of elderly people hospitalized due to different diseases. The subjects in 2018-2019 influenza season were divided into different groups according to demographic status, health conditions and hospitalization outcomes to describe and compare the distribution of influenza vaccination rates. RESULTS: The influenza vaccine coverage rates among the elderly people hospitalized due to cardiovascular diseases, cerebrovascular diseases, respiratory diseases or diabetes mellitus were 14.6%, 13.4%, 13.4% and 11.8%, respectively. The influenza vaccination rate among those hospitalized for cardiovascular diseases remained the highest across six influenza seasons and those hospitalized for diabetes mellitus remained the lowest. The largest annual decline of influenza vaccine coverage rate was observed among the hospitalized elderly due to diabetes mellitus (-7.85%). The distribution of vaccinated population was significantly associated with age, gender, hospitalization outcome and comorbidities among the hospitalized elderly people with specific diseases in 2018-2019. Among the elderly people hospitalized due to four different diseases, the vaccination rate of the patients aged 70-79 years was higher than that of the other age groups and that of the patients aged 60-69 years was the lowest. Among the elderly people hospitalized due to respiratory diseases, the vaccination rate of men was higher than that of women, while the situation reversed among the elderly people hospitalized due to cardiovascular diseases and diabetes mellitus. Vaccination rates decreased among the older adults with poor hospitalization outcomes. Among the elderly people hospitalized due to diabetes mellitus, those with 0 comorbidity had the lowest vaccination rate (7.9%). CONCLUSION: The trend of influenza vaccine coverage rates among the elderly people in Beijing from 2013 to 2019 was downward. We should pay more attention to influenza vaccination in elderly people with diabetes mellitus and aged 60-69 years, and carry out more research on the protective effects of influenza vaccine to promote influenza vaccine coverage among people with chronic diseases.

Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide.

BACKGROUND: Mutations in the androgen receptor (AR) ligand-binding domain (LBD), such as F877L and T878A, have been associated with resistance to next-generation AR-directed therapies. ARN-509-001 was a phase I/II study that evaluated apalutamide activity in castration-resistant prostate cancer (CRPC). Here, we evaluated the type and frequency of 11 relevant AR-LBD mutations in apalutamide-treated CRPC patients. PATIENTS AND METHODS: Blood samples from men with nonmetastatic CRPC (nmCRPC) and metastatic CRPC (mCRPC) pre- or post-abiraterone acetate and prednisone (AAP) treatment (≥6 months' exposure) were evaluated at baseline and disease progression in trial ARN-509-001. Mutations were detected in circulating tumor DNA using a digital polymerase chain reaction-based method known as BEAMing (beads, emulsification, amplification and magnetics) (Sysmex Inostics' GmbH). RESULTS: Of the 97 total patients, 51 had nmCRPC, 25 had AAP-naïve mCRPC, and 21 had post-AAP mCRPC. Ninety-three were assessable for the mutation analysis at baseline and 82 of the 93 at progression. The overall frequency of detected AR mutations at baseline was 7/93 (7.5%) and at progression was 6/82 (7.3%). Three of the 82 (3.7%) mCRPC patients (2 AAP-naïve and 1 post-AAP) acquired AR F877L during apalutamide treatment. At baseline, 3 of the 93 (3.2%) post-AAP patients had detectable AR T878A, which was lost after apalutamide treatment in 1 patient who continued apalutamide treatment for 12 months. CONCLUSIONS: The overall frequency of detected mutations at baseline (7.5%) and progression (7.3%) using the sensitive BEAMing assay was low, suggesting that, based on this assay, AR-LBD mutations such as F877L and T878A are not common contributors to de novo or acquired resistance to apalutamide. CLINICALTRIALS.GOV IDENTIFIER: NCT01171898.

Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC. PATIENTS AND METHODS: Patients (N = 297) were stratified by the number of prior therapies for metastatic disease (0-1 versus 2) and by prior NSAI use (adjuvant versus metastatic), and randomized (1 : 1 : 1) to receive oral once daily 1000 mg abiraterone acetate plus 5 mg prednisone (AA) versus AA with 25 mg E (AAE) versus 25 mg E alone (E). Each treatment arm was well balanced with regard to the proportion of patients with AR-positive breast cancer. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, clinical benefit rate, duration of response, and overall response rate. RESULTS: There was no significant difference in PFS with AA versus E (3.7 versus 3.7 months; hazard ratio [HR] = 1.1; 95% confidence interval [CI] 0.82-1.60; P = 0.437) or AAE versus E (4.5 versus 3.7 months; HR = 0.96; 95% CI 0.70-1.32; P = 0.794). Increased serum progesterone concentrations were observed in both arms receiving AA, but not with E. Grade 3 or 4 treatment-emergent adverse events associated with AA, including hypokalemia and hypertension, were less common in patients in the E (2.0% and 2.9%, respectively) and AA arms (3.4% and 1.1%, respectively) than in the AAE arm (5.8% for both). CONCLUSIONS: Adding AA to E in NSAI-pretreated ER+ MBC patients did not improve PFS compared with treatment with E. An AA-induced progesterone increase may have contributed to this lack of clinical activity. CLINICALTRIALSGOV: NCT01381874.

Bioinformatics-based design of a fusion vaccine with CTLA-4 variable region to combat Brucella.

Brucellosis has become a global zoonotic disease, seriously endangering the health of people all over the world. Vaccination is an effective strategy for protection against Brucella infection in livestock in developed countries. However, current vaccines are pathogenic to humans and pregnant animals, which limits their use. Therefore, it is very important to improve the safety and immune protection of Brucella vaccine. In this study, different bioinformatics approaches were carried out to predict the physicochemical properties, T/B epitope, and tertiary structure of Omp2b and Omp31. Then, these two proteins were sequentially linked, and the Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) variable region was fused to the N-terminal of the epitope sequence. In addition, molecular docking was performed to show that the structure of the fusion protein vaccine had strong affinity with B7 (B7-1, B7-2). This study showed that the designed vaccine containing CTLA-4 had high potency against Brucella, which could provide a reference for the future development of efficient brucellosis vaccines.

Bioinformatics-based design of a fusion vaccine with CTLA-4 variable region to combat Brucella

Brucellosis has become a global zoonotic disease, seriously endangering the health of people all over the world. Vaccination is an effective strategy for protection against Brucella infection in livestock in developed countries. However, current vaccines are pathogenic to humans and pregnant animals, which limits their use. Therefore, it is very important to improve the safety and immune protection of Brucella vaccine. In this study, different bioinformatics approaches were carried out to predict the physicochemical properties, T/B epitope, and tertiary structure of Omp2b and Omp31. Then, these two proteins were sequentially linked, and the Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) variable region was fused to the N-terminal of the epitope sequence. In addition, molecular docking was performed to show that the structure of the fusion protein vaccine had strong affinity with B7 (B7-1, B7-2). This study showed that the designed vaccine containing CTLA-4 had high potency against Brucella, which could provide a reference for the future development of efficient brucellosis vaccines.

Non-surgical management of microperforation induced by EMR of the stomach.

BACKGROUND: Perforation and bleeding are major complications associated with gastric endoscopic mucosal resection. Evident perforation during endoscopic mucosal resection can be managed by endoscopic clipping. However, management of microperforation is not well established. PATIENT AND METHOD: From January 2002 to June 2004, 109 early gastric cancers and 300 adenomas were treated with endoscopic mucosal resection. Iatrogenic perforations occurred in 4.16% (n=17) patients. Following exclusion of four evident perforations, microperforation was observed in 3.18% (n=13) patients. The clinical features of microperforation in patients were retrospectively reviewed. RESULTS: In a total of 13 microperforation cases, 2 patients were managed surgically. The remaining patients successfully recovered without surgical management. In the case of 11 patients without surgery, 7 experienced abdominal pain, which required analgesics, 2 patients experienced mild discomfort and 2 patients experienced no symptoms. A body temperature above 37.5 degrees C was observed in 9.1% (n=1) patients and leucocytosis above 9000 microL-1 was in 72.7% (n=8) patients. The mean duration of nasogastric tube drainage was 2.36+/-1.03 days, of fasting 4.18+/-1.17 days, of intravenous antibiotics 5.55+/-1.44 days and of hospitalisation 7.45+/-1.04 days. CONCLUSION: Microperforation induced by gastric endoscopic mucosal resection can be managed successfully using a non-surgical approach including fasting, nasogastric tube drainage and intravenous antibiotics.

C-myb Regulates Autophagy for Pulp Vitality in Glucose Oxidative Stress.

Diabetes mellitus is closely related to oral-complicated diseases by oxidative stress. This study investigates whether cellular myeloblastosis (c-myb) could protect human dental pulp cells against glucose oxidative stress and regulate autophagy activity for pulp vitality. Diabetes mellitus was induced by streptozotocin in Sprague-Dawley rats, and their pulp tissue in teeth was analyzed in terms of pulp cavity and molecules by hematoxylin and eosin and immunohistochemistry staining. Human dental pulp cells were serially subcultured and treated with glucose oxidase in the presence of elevated glucose to generate glucose oxidative stress. The replication-deficient adenovirus c-myb and small interfering RNA c-myb were introduced for c-myb expression. The pulp tissue from the diabetic rats was structurally different from normal tissue in terms of narrow pulp capacity, reduced c-myb, and dentinogenesis molecules. Glucose oxidase treatment decreased c-myb and dentinogenesis molecules (bone morphogenetic protein 2 and 7, dentin matrix protein 1, and dentin sialophosphoprotein) in human dental pulp cells. However, overexpression of c-myb by adenovirus c-myb increased dentinogenesis, autophagy molecules (autophagy protein 5, microtubule-associated protein 1A/1B-light chain 3, and Beclin-1), and cell survival via p-AMPK/AKT signaling even with glucose oxidative stress. In contrast, the lack of c-myb decreased the above molecules and cell survival by downregulating p-AMPK/AKT signaling. The results indicate that diabetes leads to irreversible damage to dental pulp, which is related to downexpression of autophagy via the p-AMPK/AKT pathway by decline of c-myb. The findings of this study provide a new insight that c-myb could ameliorate autophagy activity and that it is applicable for monitoring complicated diseases of dental pulp. The involvement of c-myb in pulp pathology could serve a therapeutic target in oral-complicated diseases.

Synergy and duality in peptide antibiotic mechanisms.

The molecular mechanisms by which peptide antibiotics disrupt bacterial DNA synthesis, protein biosynthesis, cell wall biosynthesis, and membrane integrity are diverse, yet historically have been understood to follow a theme of one antibiotic, one inhibitory mechanism. In the past year, mechanistic and structural studies have shown a rich diversity in peptide antibiotic mechanism. Novel secondary targeting mechanisms for peptide antibiotics have recently been discovered, and the mechanisms of peptide antibiotics involved in synergistic relationships with antibiotics and proteins have been more clearly defined. In apparent response to selective pressures, antibiotic-producing organisms have elegantly integrated multiple functions and cooperative interactions into peptide antibiotic design for the purpose of improving antimicrobial success.

PPARγ Maintains Homeostasis through Autophagy Regulation in Dental Pulp.

This study investigated the relevance between pulp vitality and autophagy in aged human dental pulp cells (HDPCs) and whether peroxisome proliferator-activated receptor gamma (PPARγ) affects autophagy regulation for homeostasis in the aging progress. In vivo experiments were used in human and Sprague-Dawley rat teeth obtained from young and adult individuals. Aging- and autophagy-related molecules were determined by immunohistochemistry and hematoxylin and eosin staining. HDPCs were serially subcultured until spontaneously arrested for in vitro aging, and the replication deficiency adenovirus was introduced for PPARγ overexpression. Subsequently, the effect of PPARγ on regulation of autophagy molecules, mitochondria activity, and cell viability was assessed using Western blotting, confocal microscopy, and the MTT assay, respectively. In adult pulp tissue, autophagy molecules (autophagy protein 5, microtubule-associated protein 1A/1B light chain, and Beclin-1) were increased, but aging-related (PPARγ and heme oxygenase 1 [HO-1]) and dentinogenesis (dentin sialophosphoprotein and dentin matrix acidic phosphoprotein) molecules were decreased. In aged HDPCs, autophagy and intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 were increased, while PPARγ and HO-1 were decreased. Under stimulation with lipopolysaccharide, autophagy- and aging-related molecules were differentially expressed between young and aged cells. PPARγ induced HO-1 and autophagy molecules but reduced inflammatory molecules in aged cells. In addition, PPARγ activated strong mitochondrial activity and cell viability in aging cells. Inhibition of HO-1 by tin protoporphyrin IX exacerbated autophagy and mitochondrial activity as well as cell viability in young cells. This study indicates that PPARγ maintains pulp homeostasis through the regulation of autophagy molecules during the life span of HDPCs.

Effect of beam blocking on linac head scatter factors.

PURPOSE: This study aimed to investigate the influence of beam blocking on head scatter within the context of a two-component x-ray source model. METHODS AND MATERIALS: Head scatter factors were measured for open rectangular fields defined by X and Y jaws and for fields blocked by a multileaf collimator (MLC) for a 6-MV photon beam from a Varian 2300CD accelerator. A simple formula based on consideration of linac head geometry and an x-ray source model was derived to determine when the head scatter factor for a shaped field depends only on jaw settings and when it is influenced by the blocking (cerrobend blocks or MLC) itself. RESULTS: Experimental data demonstrate that the assumption that head scatter is unaffected by the introduction of beam blocking is not always acceptable, particularly for fields blocked by an MLC. The ratios of open to blocked field dimensions were compared with simple functions characterizing the accelerator head geometry to predict changes in the behavior of head scatter factors observed experimentally. CONCLUSION: A simple formula can be used to determine when head scatter factors are influenced by beam blocking (cerrobend blocks or MLC).

Laparoscopic nephrectomy and nephroureterectomy in the pediatric patient.

The pediatric laparoscopic nephrectomy/nephroureterectomy literature is reviewed. The authors' method for pediatric nephrectomy/nephroureterectomy is presented, as well as the clinical experience from Washington University.

Analytical representation of enhanced dynamic wedge factors for symmetric and asymmetric photon fields.

The Enhanced Dynamic Wedge (EDW) presents many advantages over the physical wedge. However, in order to calculate monitor units (MUs) necessary to deliver a certain dose at a certain point, EDW factors (EDWFs) need to be determined. In this work, based on analysis of the golden segmented treatment table (GSTT) and the MU fraction model, an empirical analytic formula has been developed to calculate EDW factors for symmetric and asymmetric fields. This formalism is an extension of the MU fraction model. However in comparison with previous studies [J. P. Gibbons, Med. Phys. 25, 1411-1418 (1998) and M. Miften et al., Med. Dosim. 25, 81-86 (2000)], this formula is simpler, and easier to use. It is applicable to EDW fields of different sizes, wedge angles and different photon energies. For 6 and 18 MV beams from a Varian 21EX accelerator with 7 EDW angles (Varian Oncology Systems, Palo Alto, CA), more than 250 measured EDWFs for symmetric and asymmetric fields with different off-axis distances and field sizes were compared with model calculations. Results show that 80% and 98% of calculated EDWFs match corresponding measured values to within 0.5% and 1.0%, respectively, the maximum deviation being 1.3%.

Analytical representation of head scatter factors for shaped photon beams using a two-component x-ray source model.

An analytic representation proposed for the relative intensity distribution of the extra-focal source in a two-component x-ray source model serves as the basis for calculation. From this representation, a closed-form expression for head scatter factors defined on the central beam axis is derived by integrating over the area of the extra-focal source plane visible from the measurement point. The resulting expression is applicable to photon beams from different Varian accelerators and different photon energies, and includes effects arising from beam shaping with cerrobend blocks or multileaf collimators (MLCs). For 6- and 15-MV photon beams from Varian 600 C and 2300 CD accelerators (Varian Oncology Systems, Palo Alto, CA), 361 measured head scatter factors for square, rectangular, asymmetric, and arbitrarily shaped fields, formed by either the X and Y jaws, the MLC and Y jaws, or by the MLC alone, were compared with model calculations. Results show that 93.4% of calculated values match corresponding experimental points to within 0.5%, the average deviation being 0.23% and the maximum deviation 0.9%. Thus, as a consequence of this work, the different influence of the X jaws, the Y jaws, and the MLC on head scatter factors is quantitatively described. In particular, it is demonstrated that in the case of radially symmetric scattering, the collimator exchange effect arises as a result of the different distances of the X and Y jaws from the focal spot.

Analytical representation of head scatter factors for shaped photon beams using a two-component x-ray source model.

An analytic representation proposed for the relative intensity distribution of the extra-focal source in a two-component x-ray source model serves as the basis for calculation. From this representation, a closed-form expression for head scatter factors defined on the central beam axis is derived by integrating over the area of the extra-focal source plane visible from the measurement point. The resulting expression is applicable to photon beams from different Varian accelerators and different photon energies, and includes effects arising from beam shaping with cerrobend blocks or multileaf collimators (MLCs). For 6- and 15-MV photon beams from Varian 600C and 2300CD accelerators (Varian Oncology Systems, Palo Alto, CA), 361 measured head scatter factors for square, rectangular, asymmetric, and arbitrarily shaped fields, formed by either the X and Y jaws, the MLC and Y jaws, or by the MLC alone, were compared with model calculations. Results show that 93.4% of calculated values match corresponding experimental points to within 0.5%, the average deviation being 0.23% and the maximum deviation 0.9%. Thus, as a consequence of this work, the different influence of the X jaws, the Y jaws, and the MLC on head scatter factors is quantitatively described. In particular, it is demonstrated that in the case of radially symmetric scattering, the collimator exchange effect arises as a result of the different distances of the X and Y jaws from the focal spot.

Parametrization of head-scatter factors for rectangular photon fields using an equivalent square formalism.

Head-scatter factors of symmetric square and rectangular fields (field center on the central beam axis) defined by the upper (Y) and lower (X) jaws for 6 and 15 MV photon beams from 2300CD and 600C accelerators (Varian Associates, Inc., Palo Alto, CA) were measured, as well as those for fields shaped by the Y jaws and the multileaf collimator (MLC) of the 2300CD. For rectangular fields, the head-scatter factor for the field (x = a and y = b) was different from that for the field (y = a and x = b). This difference was 2% -3% for fields defined by conventional collimators when [formula, see text] was large, and became 4%-5% when the MLC and YT jaws were used to shape the fields with the X jaws retracted. In order to calculate values for head-scatter factors of rectangular fields accurately using an equivalent square formalism, the side of the equivalent square should be obtained with different weights for lower and upper jaws, as proposed by Vadash and Bjärngard [Med. Phys. 20, 733-734 (1993)]. Our measurements demonstrate that the relative weight (G) of upper and lower jaws is strongly dependent on their distances from the x-ray source, while the beam energy has little effect on the value of G. We further show that G can be calculated simply from these distances. An analytical representation for head-scatter factors of square and rectangular fields is also developed in this paper. The quality of this representation was judged by the root-mean-square (rms) deviation from measured head-scatter factors, which ranged from 0.11%-0.27%.

Linear accelerator photon beam quality at off-axis points.

Transmitted intensity through water was measured in a narrow-beam geometry for different energy x-ray beams from commercial accelerators. In order to accurately obtain the attenuation coefficient of the incident beam using transmission data, a novel formula was developed based on consideration of beam hardening in phantom. The value of the attenuation coefficient obtained by fitting transmission data to this formula was found to be independent of the absorber thickness used in experiments, whereas the attenuation coefficient obtained from the traditional formula, I(x) = I0 exp(-mux), changed by up to 7% with absorber thickness for a given beam. The beam hardening coefficient obtained from our formula indicates that the attenuation coefficient in water changes by about 0.33% per cm near the surface for the high-energy photon beams studied. Variations in beam quality with off-axis distance were subsequently investigated using the new formula. Results show that the attenuation coefficient at the water surface increased by about 15% for 15 and 18 MV beams, and by 11%-13% for 6 MV beams, when the off-axis distance at 100 cm from the source was changed from 0 to 18 cm. Consideration of the physics of bremsstrahlung production suggests that these variations should be mainly determined by the shape of the flattening filter, i.e., by the path length of rays traversing the filter in different directions. This expectation was confirmed by observing that the attenuation coefficient at the phantom surface can be related to the ray path of the beam in the flattening filter using the new transmission formula.

Evaluation of a commercial three-dimensional electron beam treatment planning system.

We evaluated a commercial three-dimensional (3D) electron beam treatment planning system (CADPLAN V.2.7.9) using both experimentally measured and Monte Carlo calculated dose distributions to compare with those predicted by CADPLAN calculations. Tests were carried out at various field sizes and electron beam energies from 6 to 20 MeV. For a homogeneous water phantom the agreement between measured and CADPLAN calculated dose distributions is very good except at the phantom surface. CADPLAN is able to predict hot and cold spots caused by a simple 3D inhomogeneity but unable to predict dose distributions for a more complex geometry where CADPLAN underestimates dose changes caused by inhomogeneity. We discussed possible causes for the inaccuracy in the CADPLAN dose calculations. In addition, we have tested CADPLAN treatment monitor unit and electron cut-out factor calculations and found that CADPLAN predictions generally agree with manual calculations.

Measurement of photon beam backscatter from collimators to the beam monitor chamber using target-current-pulse-counting and telescope techniques.

Backscattered radiation (BSR) arising from field-defining collimators and entering the beam monitor chamber (BMC) may contribute to observed variations in medical linear accelerator photon beam output with collimator setting. Measuring the magnitude of such contributions for particular accelerators under specified operating conditions is therefore important when attempting to understand and model accelerator head scatter. The present work was conducted to confirm some backscatter measurements for collimating jaws reported previously and to extend these to include other accelerators and a multileaf collimator (MLC). BSR reaching the BMC from the jaws of Clinac 600C, 2100C and 2300CD accelerators and from an MLC on the 2300CD was investigated using both target-current-pulse-counting and telescope methods. Our measurements show that for the Clinac 600C BSR-dependent output variations are negligible. However, for the 2100C and 2300CD BSR-dependent relative output increased in an almost linear fashion, by up to 2.4% for 15 and 18 MV beams, and by up to 1.7% for 6 MV beams, as the field size varied from 5 x 5 cm2 to 40 x 40 cm2. The magnitude of BSR dependent upon collimator location in the head, as expected, thereby contributing to the collimator exchange effect. An earlier study at our centre using the telescope method had reported higher BSR levels. This discrepancy was resolved when corrections for telescope block and room scatter, previously assumed negligible, were made.

CFTR suppresses tumor progression through miR-193b targeting urokinase plasminogen activator (uPA) in prostate cancer.

Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is expressed in the epithelial cells of a wide range of organs/tissues from which most cancers are derived. Although accumulating reports have indicated the association of cancer incidence with genetic variations in CFTR gene, the exact role of CFTR in cancer development and the possible underlying mechanism have not been elucidated. Here, we report that CFTR expression is significantly decreased in both prostate cancer cell lines and human prostate cancer tissue samples. Overexpression of CFTR in prostate cancer cell lines suppresses tumor progression (cell growth, adhesion and migration), whereas knockdown of CFTR leads to enhanced malignancies both in vitro and in vivo. In addition, we demonstrate that CFTR knockdown-enhanced cell proliferation, cell invasion and migration are significantly reversed by antibodies against either urokinase plasminogen activator (uPA) or uPA receptor (uPAR), which are known to be involved in various malignant traits of cancer development. More interestingly, overexpression of CFTR suppresses uPA by upregulating the recently described tumor suppressor microRNA-193b (miR-193b), and overexpression of pre-miR-193b significantly reverses CFTR knockdown-enhanced malignant phenotype and abrogates elevated uPA activity in prostate cancer cell line. Finally, we show that CFTR gene transfer results in significant tumor repression in prostate cancer xenografts in vivo. Taken together, the present study has demonstrated a previously undefined tumor-suppressing role of CFTR and its involvement in regulation of miR-193b in prostate cancer development.