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1.
J Cancer Res Ther ; 19(4): 945-950, 2023 Aug.
Article En | MEDLINE | ID: mdl-37675721

Background: The technique of laser en bloc resection of bladder tumor (ERBT) has been a valuable alternative technique to transurethral resection of bladder tumor (TURBT). However, the combination of laser ERBT and endoscopic submucosal dissection (ESD) technique has not been well studied. Here, a novel technique integrating a high-power green-light laser with ESD was presented. This study aimed to evaluate the safety and efficacy of high-power green-light laser endoscopic submucosal dissection (HPL-ESD) for the treatment of primary non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: From January 2015 to December 2018, a total of 56 patients with NMIBC underwent HPL-ESD. All tumors were transurethral en bloc resected in the ESD technique. Perioperative clinical data were retrospectively collected and analyzed. Results: All operations were safely performed by the technique of HPL-ESD without blood transfusion. The mean tumor diameter was 2.04 ± 0.65 cm, ranging from 0.5 to 3.5 cm. The mean operative time was 28.39 ± 16.04 min. The average serum hemoglobin decrease was 0.88 ± 0.54 g/dL. The mean postoperative catheterization time was 2.88 ± 0.94 days. The pathologic stages included pTa (32 cases), and pT1 (24 cases). Double-J stent indwelling was not performed for four patients whose tumors were adjacent to the ureteral orifice and no postoperative hydronephrosis was observed. Only one case of ectopic bladder tumor recurred due to irregular bladder irrigation during the 36-month follow-up. Conclusion: HPL-ESD is a safe and effective alternative for the treatment of primary NMIBCs, especially for tumors adjacent to the ureteral orifice.


Endoscopic Mucosal Resection , Non-Muscle Invasive Bladder Neoplasms , Urinary Bladder Neoplasms , Humans , Retrospective Studies , Urinary Bladder Neoplasms/surgery , Cystectomy
2.
Front Oncol ; 12: 1072361, 2022.
Article En | MEDLINE | ID: mdl-36741690

Background: Metastatic pheochromocytomas and paragangliomas are rare neuroendocrine tumors with a poor prognosis. Bladder paraganglioma concomitant with urothelial papilloma is even rarer. However, the rate of tumor response to cyclophosphamide-vincristine-dacarbazine (CVD) chemotherapy and 5-year overall survival for patients with metastatic PPGLs remained lower. We described, for the first time, a case of a patient with multiple metastatic bladder PGL who received octreotide LAR combined with CVD chemotherapy after urological surgery and then octreotide therapy was continued during follow-up. Case presentation: A 43-year-old male patient was admitted to the urology department for frequent micturition syncope concomitant with malignant hypertension. Preoperative findings were elevated levels of normetanephrine in 24-h urine or plasma. CT and MRI indicated diagnosis of suspicious bladder paraganglioma. Transurethral resection of bladder tumor combined with laparoscopic partial cystectomy was performed successfully after preoperative phenoxybenzamine with aggressive volume repletion for 7 days. The result of postoperative pathology was immediate-risk functional bladder paraganglioma (T2N0M0, Stage II) concomitant with urothelial papilloma, and the immunohistochemistry results of PPGL were positive for Ki-67 (15%), SDHB, CgA, and SSTR2. The patient achieved enhanced recovery with normal urination and no syncope after surgery. However, the results of 18F-FDG and 18F-DOTATATE PET/CT found that the metastatic localizations of bladder PGLs were in the liver, lung, and bones at the 8th month after surgery. The patient received octreotide long-acting repeatable plus six courses of CVD chemotherapy for 6 months, and then octreotide therapy was continued every 3 months until now. Metastatic localizations were stable in CT scans, and vanillylmandelic acid in 24-h urine was maintained at lower levels during follow-up. Conclusion: Octreotide long-acting repeatable plus CVD chemotherapy after surgery could achieve stable disease in the case with multiple metastatic bladder PGLs, and the following octreotide therapy could maintain a state of stable disease during the period of 6-month follow-up.

3.
Front Med (Lausanne) ; 8: 785331, 2021.
Article En | MEDLINE | ID: mdl-34881275

Background: Tripartite motif containing 46 was initially identified as the oncogene in several human tumors. However, the clinical value and potential functions of tripartite motif containing 46 (TRIM46) in clear cell renal cell carcinoma (ccRCC) remained largely unclear. Methods: The expressing patterns, clinical involvement, and prognostic values of TRIM46 were analyzed using the data obtained from TCGA and GEO databases. A nomogram was constructed to examine the outcome of patients with ccRCC. We estimated the association between TRIM46 with tumor immunity in ccRCC. Results: Tripartite motif containing 46 was highly expressed in ccRCC, and its upregulation revealed an unfavorable prognosis. A nomogram based on TRIM46 expressions and other independent prognostic factors could robustly predict the overall survival of tumor patients. TRIM46 has a strong positive correlation with NUMBL, CACNB1, THBS3, ROBO3, MAP3K12, ANKRD13D, PIF1, PRELID3A, ANKRD13B, and PCNX2. Mechanically, TRIM46 displayed regulatory functions in ccRCC progression via several tumor-associated pathways. Besides, we observed that TRIM46 was distinctly related to tumor immunity in ccRCC. Conclusions: Our findings provide a novel tumor promotive role regarding TRIM46 function in the malignant progression of ccRCC.

4.
J Cancer Res Ther ; 17(3): 625-629, 2021 Jul.
Article En | MEDLINE | ID: mdl-34269291

AIMS: This study aimed to evaluate the role of serum prostate-specific antigen (PSA) levels and multiparametric magnetic resonance imaging (mpMRI) in the diagnosis of granulomatous prostatitis (GP) induced by intravesical Bacillus Calmette-Guérin vaccine (BCG) therapy in patients with nonmuscle invasive bladder cancer (NMIBC). SUBJECTS AND METHODS: We retrospectively analyzed eight patients with bladder cancer who underwent intravesical BCG therapy after transurethral resection of bladder tumor (TURBt) cancer. All these eight patients received 12-core transrectal ultrasound-guided prostate systemic biopsies. Clinical data on PSA with T1-weighted imaging (T1WI), T2WI, diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) on mpMRI were enrolled in the study. H and E and acid-fast staining was performed to pathologically prove GP. RESULTS: Four of all eight cases were above 4 ng/ml total PSA (tPSA) levels and four cases were within normal ranges, while free PSA/tPSA levels decreased to lower than 16% in all patients. Every patient had hard prostatic nodules through digital rectal examination (DRE). All characters of prostate mpMRI did not show signal intensity (SI) of prostate cancer before BCG therapy but showed abnormal signals after BCG therapy. All nodular lesions showed equal SI on T1WI, lower SI on T2WI, higher SI on DWI, and lower SI on ADC after BCG therapy. Pathologic results were GP and acid-fast staining outcomes were positive in all biopsies. CONCLUSIONS: Perioperative serum PSA levels, prostate magnetic resonance imaging, and DRE may help in the diagnosis of GP induced by intravesical BCG therapy. In general, male patients with middle- and high-risk NMIBC are recommended to undertake DRE, PSA, and prostate mpMRI, if possible, before and after TURBt."


BCG Vaccine/adverse effects , Kallikreins/blood , Prostate-Specific Antigen/blood , Prostate/diagnostic imaging , Prostatitis/diagnosis , Urinary Bladder Neoplasms/therapy , Administration, Intravesical , Aged , BCG Vaccine/administration & dosage , Biomarkers/blood , Biopsy , Cystectomy , Digital Rectal Examination , Humans , Immunotherapy/adverse effects , Immunotherapy/methods , Male , Middle Aged , Multiparametric Magnetic Resonance Imaging , Prostate/pathology , Prostatitis/blood , Prostatitis/immunology , Prostatitis/pathology , Retrospective Studies , Urinary Bladder Neoplasms/pathology
5.
Medicine (Baltimore) ; 100(11): e24949, 2021 Mar 19.
Article En | MEDLINE | ID: mdl-33725966

ABSTRACT: Currently, no effective prognostic model of clear cell renal cell carcinoma (ccRCC) based on immune cell infiltration has been developed. Recent studies have identified 6 immune groups (IS) in 33 solid tumors. We aimed to characterize the expression pattern of IS in ccRCC and evaluate the potential in predicting patient prognosis. The clinical information, immune subgroup, somatic mutation, copy number variation, and methylation score of patients with TCGA ccRCC cohort were downloaded from UCSC Xena for further analysis. The most dominant IS in ccRCC was the inflammatory subgroup (immune C3) (86.5%), regardless of different pathological stages, pathological grades, and genders. In the C3 subgroup, stage IV (69.1%) and grade 4 (69.9%) were the least presented. Survival analysis showed that the IS could effectively predict the overall survival (OS) (P < .0001) and disease-specific survival (DSS) (P < .0001) of ccRCC alone, of which group C3 (OS, HR = 2.3, P < .001; DSS, HR = 2.84, P < .001) exhibited the best prognosis. Among the most frequently mutated ccRCC genes, only VHL and PBRM1 were found to be common in the C3 group. The homologous recombination deficiency score was also lower. High heterogeneity was observed in immune cells and immunoregulatory genes of IS. Notably, CD4+ memory resting T cells were highly infiltrating, regulatory T cells (Treg) showed low infiltration, and most immunoregulatory genes (such as CX3CL1, IFNA2, TLR4, SELP, HMGB1, and TNFRSF14) were highly expressed in the C3 subgroup than in other subgroups. Enrichment analysis showed that adipogenesis, apical junction, hypoxia, IL2 STAT5 signaling, TGF-beta signaling, and UV response DN were activated, whereas E2F targets, G2M checkpoint, and MYC targets V2 were downregulated in the C3 group. Immune classification can more accurately classify ccRCC patients and predict OS and DSS. Thus, IS-based classification may be a valuable tool that enables individualized treatment of patients with ccRCC.


Carcinoma, Renal Cell/classification , Immunophenotyping/methods , Kidney Neoplasms/classification , Lymphocyte Subsets/immunology , Tumor Microenvironment/immunology , Biomarkers, Tumor/immunology , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/mortality , Chemokine CX3CL1 , DNA Copy Number Variations/immunology , DNA-Binding Proteins , Gene Expression Regulation, Neoplastic/immunology , HMGB1 Protein , Humans , Interferon-alpha , Kidney Neoplasms/immunology , Kidney Neoplasms/mortality , Lymphocytes, Tumor-Infiltrating/immunology , Methylation , Mutation/immunology , Neoplasm Grading , Neoplasm Staging , P-Selectin , Predictive Value of Tests , Prognosis , Receptors, Tumor Necrosis Factor, Member 14 , Signal Transduction/immunology , Survival Analysis , Toll-Like Receptor 4 , Transcription Factors , Von Hippel-Lindau Tumor Suppressor Protein
6.
Ther Adv Urol ; 13: 1756287220984046, 2021.
Article En | MEDLINE | ID: mdl-33633798

AIMS: Management of inflammatory renal disease (IRD) can still be technically challenging for laparoscopic procedures. The aim of the present study was to compare the safety and feasibility of laparoscopic and hand-assisted laparoscopic nephrectomy in patients with IRD. PATIENTS AND METHODS: We retrospectively analyzed the data of 107 patients who underwent laparoscopic nephrectomy (LN) and hand-assisted laparoscopic nephrectomy (HALN) for IRD from January 2008 to March 2020, including pyonephrosis, renal tuberculosis, hydronephrosis, and xanthogranulomatous pyelonephritis. Patient demographics, operative outcomes, and postoperative recovery and complications were compared between the LN and HALN groups. Multivariable logistic regression analysis was conducted to identify the independent predictors of adverse outcomes. RESULTS: Fifty-five subjects in the LN group and 52 subjects in the HALN group were enrolled in this study. In the LN group, laparoscopic nephrectomy was successfully performed in 50 patients (90.9%), while four (7.3%) patients were converted to HALN and one (1.8%) case was converted to open procedure. In HALN group, operations were completed in 51 (98.1%) patients and conversion to open surgery was necessary in one patient (1.9%). The LN group had a shorter median incision length (5 cm versus 7 cm, p < 0.01) but a longer median operative duration (140 min versus 105 min, p < 0.01) than the HALN group. There was no significant difference in blood loss, intraoperative complication rate, postoperative complication rate, recovery of bowel function, and hospital stay between the two groups. Multivariable logistic regression revealed that severe perinephric adhesions was an independent predictor of adverse outcomes. CONCLUSION: Both LN and HALN appear to be safe and feasible for IRD. As a still minimally invasive approach, HALN provided an alternative to IRD or when conversion was needed in LN.

7.
Gynecol Endocrinol ; 37(1): 97-100, 2021 Jan.
Article En | MEDLINE | ID: mdl-32945709

Mutations of the CYP17A1 gene could cause complete or partial and combined or isolated 17α-hydroxylase/17,20-lyase deficiency (17OHD), which is characterized by hypertension, hypokalemia, and abnormal development of the genitalia. Most of the mutations are located in the coding sequence, and very few are located in the intronic region. The aim of this study is to investigate the novel intronic CYP17A1 mutation and its possible influence on phenotype. A 30-year-old Chinese female patient (46, XY) was referred to our Urology Department for severe hypertension, hypokalemia and a right adrenal mass. Physical examination revealed a hypertrophic clitoris and blind-ending vagina. Hormone analysis exhibited increased concentrations of ACTH and low levels of cortisol and sexual steroids. Mutation analysis revealed compound heterozygous CYP17A1 mutations, with c.1072C > T (p.Arg358*) in one allele and a novel intronic splicing mutation (c.970-1G > A) in another allele. Bioinformatics software predicted that the novel mutation may activate a cryptic splice site, shifting the reading frame and introducing a premature stop codon. In conclusion, we discovered a novel splicing mutation of the CYP17A1 gene in a Chinese patient with 17OHD. Our study extended the CYP17A1 mutation spectrum and provided valuable information for patient management and genetic counseling.


Adrenal Hyperplasia, Congenital/genetics , Cytochrome P-450 Enzyme System/deficiency , RNA Splice Sites/genetics , Steroid 17-alpha-Hydroxylase/genetics , Adult , Codon, Nonsense , Cytochrome P-450 Enzyme System/genetics , Female , Humans , Introns
9.
Aging (Albany NY) ; 12(24): 25356-25372, 2020 11 20.
Article En | MEDLINE | ID: mdl-33229623

Dysregulated expression of RNA-binding proteins (RBPs) is strongly associated with the development and progression of multiple tumors. However, little is known about the role of RBPs in kidney renal clear cell carcinoma (KIRC). In this study, we examined RBP expression profiles using The Cancer Genome Atlas database and identified 133 RBPs that were differentially expressed in KIRC and non-tumor tissues. We then systematically analyzed the potential biological functions of these RBPs and established PPIs. Based on Lasso regression and Cox survival analyses, we constructed a risk model that could independently and accurately predict prognosis based on seven RBPs (NOL12, PABPC1L, RNASE2, RPL22L1, RBM47, OASL, and YBX3). Survival times were shorter in patients with high risk scores for cohorts stratified by different characteristics. Gene set enrichment analysis was also performed to further understand functional differences between high- and low-risk groups. Finally, we developed a clinical nomogram with a concordance index of 0.792 for estimating 3- and 5-year survival probabilities. Our results demonstrate that this risk model could potentially improve individualized diagnostic and therapeutic strategies.


Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/metabolism , RNA-Binding Proteins/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/mortality , Gene Expression Regulation, Neoplastic/physiology , Gene Regulatory Networks , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/mortality , Nomograms , Prognosis , Transcriptome
10.
J Int Med Res ; 48(10): 300060520961238, 2020 Oct.
Article En | MEDLINE | ID: mdl-33044120

OBJECTIVE: To compare the operative and oncologic outcomes between hand-assisted laparoscopic radical nephrectomy (HALRN) and laparoscopic radical nephrectomy (LRN) for large (stage ≥T2b) and locally advanced renal cell carcinoma. METHODS: We retrospectively collected data from patients who underwent HALRN or LRN for stage ≥T2b renal cell carcinoma from January 2011 to January 2018 in our institution. The patients' demographics, perioperative parameters, and postoperative follow-up data were compared between the two groups. The survival outcome was estimated using the Kaplan-Meier method. RESULTS: The HALRN group comprised 78 patients, and the LRN group comprised 63 patients. The median operative duration was significantly shorter in the HALRN than LRN group. The two groups were equivalent in terms of the incision length, blood loss, complication rate, and duration of hospitalization. In the HALRN and LRN groups, the 5-year overall survival rates were 69.4% and 73.1%, the 5-year cancer-specific survival rates were 80.0% and 83.3%, and the 5-year progression-free survival rates were 66.4% and 74.7%, respectively, with no significant differences. CONCLUSIONS: Compared with LRN, HALRN may offer a shorter operative duration and equivalent surgical outcomes without sacrificing oncological efficacy. In addition, HALRN has specific advantages for extremely large and complicated renal tumors.


Carcinoma, Renal Cell , Hand-Assisted Laparoscopy , Kidney Neoplasms , Laparoscopy , Carcinoma, Renal Cell/surgery , Humans , Kidney Neoplasms/surgery , Nephrectomy , Retrospective Studies , Treatment Outcome
11.
Biomed Res Int ; 2020: 1932948, 2020.
Article En | MEDLINE | ID: mdl-32461965

Clear cell renal cell carcinoma (ccRCC) is the most common lethal subtype of renal cancer, and changes in tumor metabolism play a key role in its development. Solute carriers (SLCs) are important in the transport of small molecules in humans, and defects in SLC transporters can lead to serious diseases. The expression patterns and prognostic values of SLC family transporters in the development of ccRCC are still unclear. The current study analyzed the expression levels of SLC family members and their correlation with prognosis in ccRCC patients with data from Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), cBioPortal, the Human Protein Atlas (HPA), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO). We found that the mRNA expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly lower in ccRCC tissues than in normal tissues and the protein expression levels of SLC22A6, SLC22A7, SLC22A13, and SLC34A1 were also significantly lower. Except for SLC22A7, the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were correlated with the clinical stage of ccRCC patients. The lower the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were, the later the clinical stage of ccRCC patients was. Further experiments revealed that the expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly associated with overall survival (OS) and disease-free survival (DFS) in ccRCC patients. High SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 expression predicted improved OS and DFS. Finally, GSE53757 and ICGC were used to revalidate the differential expression and clinical prognostic value. This study suggests that SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 may be potential targets for the clinical diagnosis, prognosis, and treatment of ccRCC patients.


Carcinoma, Renal Cell , Kidney Neoplasms , Solute Carrier Proteins , Adult , Aged , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/metabolism , Female , Humans , Kidney/chemistry , Kidney/metabolism , Kidney Neoplasms/diagnosis , Kidney Neoplasms/metabolism , Male , Middle Aged , Prognosis , Protein Interaction Maps/genetics , Solute Carrier Proteins/analysis , Solute Carrier Proteins/genetics , Solute Carrier Proteins/metabolism , Transcriptome/genetics
12.
BMC Surg ; 19(1): 167, 2019 Nov 11.
Article En | MEDLINE | ID: mdl-31711457

BACKGROUND: Abdominal cocoon is a rare peritoneal lesion and is difficult to diagnose because of its lack of special clinical manifestations. Until now, there is no case report of abdominal cocoon combined with cryptorchidism and seminoma. CASE PRESENTATION: A case of abdominal cocoon with cryptorchidism and seminoma was diagnosed and treated in our hospital. The patient had no symptoms except occasional abdominal pain. He underwent laparoscopy because of bilateral cryptorchidism and seminoma in the right testis. During the surgery, he was diagnosed with abdominal cocoon due to the thick fibrous tissues which was tightly adhered and encased part of intestine like a cocoon. Enterolysis and bilateral cryptochiectomy were performed after the diagnosis and nutritional and symptomatic support was provided after the surgery. The patient recovered well and was discharged soon. The postoperative pathological examination confirmed the presence of bilateral cryptorchidism and seminoma in the patient's right testis. CONCLUSION: There are only a handful of cases where a patient has both abdominal cocoon and cryptorchidism. Since the etiologies of both diseases remain unknown, further research is required to investigate effective diagnosis and treatment for the diseases and explore the potential connection between the two diseases.


Cryptorchidism/diagnosis , Seminoma/diagnosis , Testicular Neoplasms/diagnosis , Abdominal Pain/diagnosis , Abdominal Pain/etiology , Adult , Cryptorchidism/complications , Cryptorchidism/surgery , Diagnosis, Differential , Humans , Laparoscopy/methods , Magnetic Resonance Imaging , Male , Scrotum , Seminoma/complications , Seminoma/surgery , Testicular Neoplasms/complications , Testicular Neoplasms/surgery , Ultrasonography , Urologic Surgical Procedures, Male/methods
13.
Medicine (Baltimore) ; 97(27): e11445, 2018 Jul.
Article En | MEDLINE | ID: mdl-29979446

To investigate the best surgical occasion of laparoscopic cyst decortications (LCDs) in patients with autosomal dominant polycystic kidney disease (ADPKD), in accordance with the renal volume (RV). We retrospectively analyzed 135 (65 male and 70 female) patients with ADPKD who underwent LCD between June 2011 and October 2015. Patients were divided into 4 groups according to the volume of the operated kidney measured from computed tomography scans: group A (28 patients, RV < 500 mL), group B (63 patients, RV = 500-1000 mL), group C (30 patients, RV = 1000-1500 mL), and group D (14 patients, RV > 1500 mL). We studied postoperative indicators at least 1-year follow-up. For each RV group, therapeutic responses of LCD in these patients with ADPKD were assessed by improvement of clinical parameters and manifestations. A significant glomerular filtration rate (GFR) improvement was found in RV group B (31.8 ±â€Š11.1 mL/min; final GFR 36.9 ±â€Š12.7 mL/min; P < 0.01), and RV group C (21.1 ±â€Š8.7 mL/min; final GFR 27.4 ±â€Š9.2 mL/min; P < 0.01). RV group C had much higher GFR improvements than did RV group B (P < 0.01). In addition, refractory pain in patients of RV groups B, C, and D was much relieved by LCD treatment. Compared with other RV groups, blood pressures in patients with ADPKD of RV group D were also improved (P < 0.01). Our study indicates that RV could be used to evaluate LCD clinical outcomes in patients with ADPKD. The results of LCD for patients with ADPKD with RV between 500 and 1500 mL were encouraging, especially with regards to renal function improvement and pain relief. Therefore, RV may become a useful marker to predict the timing of LCD surgery in patients with ADPKD.


Kidney/surgery , Laparoscopy/methods , Polycystic Kidney, Autosomal Dominant/surgery , Adult , Arterial Pressure , Biomarkers , Female , Glomerular Filtration Rate , Humans , Kidney/diagnostic imaging , Kidney/physiopathology , Laparoscopy/adverse effects , Male , Middle Aged , Pain Measurement , Postoperative Complications/epidemiology , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
14.
Mol Cell Biochem ; 434(1-2): 135-142, 2017 Oct.
Article En | MEDLINE | ID: mdl-28470345

This study was to investigate the involvement of long non-coding RNA (lncRNA) colon cancer-associated transcript-1 (CCAT1) in renal cell carcinoma (RCC) and to further uncover its underlying mechanism. In this study, the expression of CCAT1 and Livin of RCC tissues or cells was determined using qRT-PCR (quantitative real-time PCR) and western blot, respectively. RNA pulldown and RIP (RNA-Binding Protein Immunoprecipitation) assays were performed to examine the sequence interaction between CCAT1 and Livin. The viability and apoptosis of RCC cells was assessed by MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and TUNEL (TdT-mediated dUTP nick end labeling) assays, respectively. Mice of tumor animal models were established to observe the effect of CCAT1 on RCC tumor growth. The relative expression of CCAT1 in RCC tissues and cell lines was obviously higher than that of the control. CCAT1 knockdown could reduce cell viability and increase the apoptosis of RCC cells in vitro. Furthermore, Livin was significantly inhibited by CCAT1 silencing; RNA pulldown and RIP assays showed that CCAT1 was physically associated with Livin protein. Moreover, Livin overexpression not only significantly inhibited RCC cell apoptosis and increased cell viability, but completely reversed the si-CCAT1-mediated repression of cell viability. More importantly, CCAT1 silencing could inhibit the growth of RCC in vivo that was accompanied by the reduction of Livin in RCC tissues. CCAT1 inhibits RCC cell apoptosis and increases cell viability through up-regulation of Livin.


Adaptor Proteins, Signal Transducing/metabolism , Apoptosis/genetics , Carcinoma, Renal Cell/pathology , Inhibitor of Apoptosis Proteins/metabolism , Kidney Neoplasms/pathology , Neoplasm Proteins/metabolism , RNA, Long Noncoding/genetics , Up-Regulation , Humans
15.
Mol Oncol ; 7(6): 1019-30, 2013 Dec.
Article En | MEDLINE | ID: mdl-23916135

PURPOSE: Metastasis, the main cause of death from cancer, remains poorly understood at the molecular level. EXPERIMENTAL DESIGN: Based on a pattern of reduced expression in human prostate cancer tissues and tumor cell lines, a candidate suppressor gene (SPARCL1) was identified. We used in vitro approaches to determine whether overexpression of SPARCL1 affects cell growth, migration, and invasiveness. We then employed xenograft mouse models to analyze the impact of SPARCL1 on prostate cancer cell growth and metastasis in vivo. RESULTS: SPARCL1 expression did not inhibit tumor cell proliferation in vitro. By contrast, SPARCL1 did suppress tumor cell migration and invasiveness in vitro and tumor metastatic growth in vivo, conferring improved survival in xenograft mouse models. CONCLUSIONS: We present the first in vivo data suggesting that SPARCL1 suppresses metastasis of prostate cancer.


Calcium-Binding Proteins/biosynthesis , Extracellular Matrix Proteins/biosynthesis , Gene Expression Regulation, Neoplastic , Prostatic Neoplasms/metabolism , Tumor Suppressor Proteins/biosynthesis , Animals , Calcium-Binding Proteins/genetics , Cell Line, Tumor , Extracellular Matrix Proteins/genetics , Heterografts , Humans , Male , Meta-Analysis as Topic , Mice , Mice, SCID , Neoplasm Metastasis , Neoplasm Transplantation , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Tumor Suppressor Proteins/genetics
16.
PLoS One ; 8(1): e54979, 2013.
Article En | MEDLINE | ID: mdl-23383020

BACKGROUND: Robust transcriptional signatures in cancer can be identified by data similarity-driven meta-analysis of gene expression profiles. An unbiased data integration and interrogation strategy has not previously been available. METHODS AND FINDINGS: We implemented and performed a large meta-analysis of breast cancer gene expression profiles from 223 datasets containing 10,581 human breast cancer samples using a novel data similarity-based approach (iterative EXALT). Cancer gene expression signatures extracted from individual datasets were clustered by data similarity and consolidated into a meta-signature with a recurrent and concordant gene expression pattern. A retrospective survival analysis was performed to evaluate the predictive power of a novel meta-signature deduced from transcriptional profiling studies of human breast cancer. Validation cohorts consisting of 6,011 breast cancer patients from 21 different breast cancer datasets and 1,110 patients with other malignancies (lung and prostate cancer) were used to test the robustness of our findings. During the iterative EXALT analysis, 633 signatures were grouped by their data similarity and formed 121 signature clusters. From the 121 signature clusters, we identified a unique meta-signature (BRmet50) based on a cluster of 11 signatures sharing a phenotype related to highly aggressive breast cancer. In patients with breast cancer, there was a significant association between BRmet50 and disease outcome, and the prognostic power of BRmet50 was independent of common clinical and pathologic covariates. Furthermore, the prognostic value of BRmet50 was not specific to breast cancer, as it also predicted survival in prostate and lung cancers. CONCLUSIONS: We have established and implemented a novel data similarity-driven meta-analysis strategy. Using this approach, we identified a transcriptional meta-signature (BRmet50) in breast cancer, and the prognostic performance of BRmet50 was robust and applicable across a wide range of cancer-patient populations.


Breast Neoplasms/genetics , Gene Expression Profiling/methods , Analysis of Variance , Breast Neoplasms/pathology , Cluster Analysis , Humans
17.
J Exp Clin Cancer Res ; 32: 9, 2013 Feb 13.
Article En | MEDLINE | ID: mdl-23406686

BACKGROUND: Although a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association. METHODS: We systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords "metabolic syndrome" and "prostate cancer". We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs). RESULTS: The literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96). CONCLUSIONS: The overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required.


Metabolic Syndrome/epidemiology , Prostatic Neoplasms/epidemiology , Cohort Studies , Humans , Longitudinal Studies , Male , Neoplasm Grading , Neoplasm Recurrence, Local/epidemiology , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Risk Factors
18.
Gene ; 510(2): 180-4, 2012 Dec 01.
Article En | MEDLINE | ID: mdl-22975209

The reduced folate carrier (RFC1) plays a crucial role in mediating folate delivery into a variety of cells. RFC1 polymorphism (A80G) has been reported to be associated with increased risk of neural tube defects (NTDs). However, results derived from individually underpowered studies are conflicting. We performed a systematic search of MEDLINE and EMBASE databases and carried out a meta-analysis on the association between RFC1 polymorphism (A80G) and NTDs risk. Overall, a significant correlation between RFC1 A80G polymorphism and NTDs risk was found neither in infants nor in maternal (allele contrast in infants: OR(RE)=1.15, 95% CI: 0.92-1.45; allele contrast in mothers: OR(RE)=1.24, 95% CI: 0.98-1.56). The present meta-analysis failed to support a positive association between RFC1 A80G polymorphism and susceptibility to NTDs. It is important to realize, however, that socio-economic factors, and gene-environment and gene-gene interactions, could have influenced the outcome of our meta-analysis. For this reason, a relationship between the A80G polymorphism and NTD risk cannot be entirely discounted.


Genetic Predisposition to Disease , Neural Tube Defects/genetics , Reduced Folate Carrier Protein/genetics , Humans , Polymorphism, Genetic
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