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This study retrospectively examines the effectiveness of low-frequency electrical stimulation for addressing nocturia in patients experiencing urinary incontinence after undergoing radical prostatectomy. We reviewed the outcomes of 32 patients who had undergone radical prostatectomy and subsequently experienced urinary incontinence. These patients were divided into the control group (n = 16) who received pelvic floor muscle training and the treatment group (n = 16) who underwent electrophysiological appropriate technique treatment in conjunction with pelvic floor muscle training. We assessed changes in nocturnal voided volume, polyuria index, and nocturia-related quality of life at three different time points: before treatment, after 2 weeks, and at the 3-month follow-up. After 3-month follow-up, both groups exhibit reductions in nocturnal voided volume, and polyuria index compared with baseline and the 2-week mark (p < .05). Treatment group outperformed the control group (p < .05). The quality of life in the treatment group remained consistently high, while the control group did not show a statistically significant difference from baseline (p > .05). The total effective rate was significantly higher in the treatment group (93.75%) than in the control group (75.00%, p = .044). This retrospective analysis suggests that electrophysiological appropriate technique treatment effectively mitigates nocturnal, leading to improved quality of life in patients with urinary incontinence following radical prostatectomy in the near term.
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Noctúria , Prostatectomia , Qualidade de Vida , Humanos , Masculino , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Estudos Retrospectivos , Noctúria/etiologia , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Terapia por Estimulação Elétrica , Neoplasias da Próstata/cirurgia , Incontinência Urinária/etiologiaRESUMO
Objective: To systematically identify and quantify the incidence and risk factors of postoperative urinary incontinence (UI) in holmium laser enucleation of the prostate (HoLEP), aiming to provide a basis for intervention strategies. Methods: Relevant studies on postoperative UI in HoLEP were searched in databases including PubMed, Web of Science, EMBase, CNKI, Wanfang Data Knowledge Service Platform, VIP and CBMdisc, with the search period up to April 2024. Titles, abstracts and full texts were screened using the Endnote application. Studies meeting the inclusion and exclusion criteria underwent quality assessment and data extraction. The incidence of postoperative UI and/or adjusted or unadjusted odds ratios (OR), relative risks or ratios were recorded, and analysis was conducted using Stata 15.0 software. Results: A total of 17 studies encompassing 7939 patients were included. The pooled incidence of UI after HoLEP was 1.12, 95% CI (1.11-1.13); the 3-month postoperative incidence was 1.06, 95% CI (1.05-1.06); the 6-month postoperative incidence was 1.04, 95% CI (1.03-1.05); the 12-month postoperative incidence was 1.05, 95% CI (1.03-1.06); and the incidence of permanent UI after HoLEP was 1.01, 95% CI (1.00-1.01). The occurrence of UI after HoLEP exhibited a time-dependent variation. The risk factors for UI after HoLEP included the following: age (OR = 1.03, 95% CI: 1.01-1.06); body mass index (BMI; OR = 1.10, 95% CI: 1.01-1.20); prostate volume (OR = 1.77, 95% CI: 1.39-2.27); prostate-specific antigen (PSA) (OR = 0.98, 95% CI: 0.87-0.92); International Prostate Symptom Score (IPSS) (OR = 0.94, 95% CI: 0.83-1.07). Conclusion: The results of this study indicate a decreasing trend in the incidence of postoperative UI after HoLEP over time, with a time-dependent change. Age, BMI, prostate volume, PSA and IPSS are risk factors for postoperative UI after HoLEP. Age and prostate volume have a significant impact on UI. Therefore, preoperative assessment and intervention for these factors are crucial in reducing the occurrence of postoperative UI in HoLEP.
Postoperative urinary incontinence incidence and risk factors in HoLEP The results of this study indicate a decreasing trend in the incidence of postoperative urinary incontinence after HoLEP over time, with a time-dependent change. Age, body mass index, prostate volume, diabetes and preoperative urinary retention are risk factors for postoperative urinary incontinence after HoLEP. Age and prostate volume have a significant impact on urinary incontinence. Therefore, preoperative assessment and intervention for these factors are crucial in reducing the occurrence of postoperative urinary incontinence in HoLEP.
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Background: Prostate cancer (PCa) incidence and mortality rates are rising, necessitating precise prognostic tools to guide personalized treatment. Dysregulation of programmed cell death pathways in tumor suppression and cancer development has garnered increasing attention, providing a new research direction for identifying biomarkers and potential therapeutic targets. Methods: Integrating multiple database resources, we constructed and optimized a prognostic signature based on the expression of programmed cell death-related genes (PCDRG) using ten machine learning algorithms. Model performance and prognostic effects were further evaluated. We analyzed the relationships between signature and clinicopathological features, somatic mutations, drug sensitivity, and the tumor immune microenvironment, and constructed a nomogram. The expression level of PCDRGs were evaluated and compared. Results: Of 1560 PCDRGs, 149 were differentially expressed in PCa, with 34 associated with biochemical recurrence. The PCDRG-derived index (PCDI), constructed using the random forest algorithm, exhibited optimal prognostic performance, successfully stratifying PCa patients into two groups with significant prognostic differences. Patients with high PCDI scores exhibited poorer survival and lower immunotherapy benefit. PCDI was closely associated with the infiltration of specific immune cells, particularly positive correlations with macrophages and T helper cells, and negative correlations with neutrophils, suggesting that PCDI may influence the tumor immune microenvironment, thereby affecting patient prognosis and treatment response. PCDI was associated with age, pathological stage, somatic mutations, and drug sensitivity. The PCDI-based nomogram demonstrated excellent performance in predicting biochemical recurrence in PCa patients. Finally, the differential expression of these PCDRGs was verified based on cell lines and PCa patient expression profile data. Conclusion: This study developed an effective prognostic indicator for prostate cancer, PCDI, using machine learning approaches. PCDI reflects the link between aberrant programmed cell death pathways and disease progression and treatment response.
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Objective: To explore the potential imaging biomarkers for predicting Traditional Chinese medicine (TCM) deficiency and excess syndrome in prostate cancer (PCa) patients by radiomics approach based on MR imaging. Methods: A total of 121 PCa patients from 2 centers were divided into 1 training cohort with 84 PCa patients and 1 validation cohort with 37 PCa patients. The PCa patients were divided into deficiency and excess syndrome group according to TCM syndrome differentiation. Radiomic features were extracted from T2-weighted imaging (T2WI), diffusion-weighted imaging and apparent diffusion coefficient images originated from diffusion-weighted imaging. A radiomic signature was constructed after reduction of dimension in training group by the minimum redundancy maximum relevance and the least absolute shrinkage and selection operator. The performance of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve. Results: The radiomic scores of PCa with TCM excess syndrome group were statistically higher than those of PCa with TCM deficiency syndrome group among T2WI, diffusion-weighted imaging and apparent diffusion coefficient imaging models. The area under ROC curves for T2WI, diffusion-weighted imaging and apparent diffusion coefficient imaging models were 0.824, 0.824, 0.847 in the training cohort and 0.759, 0.750, 0.809 in the validation cohort, respectively. The apparent diffusion coefficient imaging model had the best discrimination in separating patients with TCM excess syndrome and deficiency syndrome, and its accuracy was 0.788, 0.778 in the training and validation cohort, respectively. The calibration curve demonstrated that there was a high consistency between the prediction of radiomic scores and the actual classification of TCM's deficiency and excess syndrome in PCa. Conclusion: The radiomic signature based on MR imaging can be performed as a non-invasive, potential approach to discriminate TCM deficiency syndrome from excess syndrome in PCa, in which apparent diffusion coefficient imaging model has the best diagnostic efficiency.
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Kidney renal clear cell carcinoma (KIRC) is a frequent malignant tumor characterized by a high degree of heterogeneity and genetic instability. DNA double-strand breaks generated by homologous recombination deficit (HRD) are a well-known contributor to genomic instability, which can encourage tumor development. It is not known, however, whether the molecular characteristics linked with HRD have a predictive role in KIRC. The discovery cohort comprised 501 KIRC patients from The Cancer Genome Atlas database. Genome and transcriptome data of HRD patients were used for comprehensive analysis. Single cell RNA sequencing (scRNA-seq) was used to verify the test results of bulk RNA-seq. In the present study, patients with a high HRD score had a worse prognosis compared with those with a low HRD score. The DNA damage response signaling pathways and immune-related signaling pathways were notably enriched in the HRD-positive subgroup. Further comprehensive analysis of the tumor microenvironment (TME) revealed that the signal of exhausted CD8+ T cells was enriched in the HRD-positive subgroup. Finally, scRNA-seq analyses confirmed that the immune-related signaling pathways were upregulated in HRD-positive patients. In conclusion, the present study not only demonstrated that a high HRD score is a valid prognostic biomarker in KIRC patients, but also revealed the TME in HRD-positive tumors.
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To evaluate the clinical efficacy of pelvic floor low-frequency electrical stimulation combined with anus lifting training in the treatment of urinary incontinence after radical prostatectomy in a Chinese cohort. Fifty-five patients with urinary incontinence after radical prostatectomy were randomly divided into treatment group and control group. Patients in control group received only anus lifting training therapy, while treatment group combined with pelvic floor low-frequency electrical stimulation. The urinary control including urinary incontinence questionnaire (ICI-Q-SF), urinary incontinence quality of life (I-QOL), visual analogue scale (VAS), and pelvic floor muscle strength assessment (Glazer) of the two groups of patients before treatment and every week was recorded for statistical analysis. There was a statistically significant difference between treatment group and control group in the urinary control curve. The scores of ICI-Q-SF, I-QOL, VAS, and Glazer in the treatment group after 2 weeks were statistically different from those before treatment, and effects were accumulating with the extension of treatment time. Compared with the control group, the scores of treatment group in the 2 to 10 weeks improved more significantly. Especially, in the sixth week, total effective rate of treatment group was significantly better than that of control group (74.07% [20/27], 35.71% [10/28], p < .05). The difference between two groups gradually narrowed after 10 weeks and no significant difference after 10 weeks of treatment between two groups. Pelvic floor low-frequency electrical stimulation combined with anus lifting training after radical prostatectomy can significantly shorten the recovery time of urinary incontinence in patients after radical prostatectomy.
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Qualidade de Vida , Incontinência Urinária , Masculino , Humanos , Canal Anal , População do Leste Asiático , Remoção , Prostatectomia/efeitos adversos , Incontinência Urinária/etiologia , Incontinência Urinária/terapia , Estimulação ElétricaAssuntos
Asiático , Racismo , Humanos , China , National Institutes of Health (U.S.) , Estados UnidosRESUMO
US universities must proactively address potential concerns.
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While it is widely accepted that the Chinese Communist Party (CCP) occupies a dominant position in the Chinese political system, few studies have demonstrated CCP's dominant position based on rigorous statistical analysis. Our paper presents the first such analysis using an innovative measure of regulatory transparency in the food industry across nearly 300 prefectures in China over 10 years. We show that actions by the CCP, while broadly scoped and not targeting the food industry, significantly improved regulatory transparency in the industry. In sharp contrast, food-industry-specific interventions by the State Council, which exercises direct regulatory supervision of the industry, had no impact on regulatory transparency. These results hold in various specifications and robustness checks. Our research contributes to research in China's political system by empirically and explicitly demonstrating the dominating power of the CCP.
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BACKGROUND: Castration-resistant prostate cancer (CRPC) is a major cause of recurrence and mortality among prostate cancer (PCa) patients. Myeloid-derived suppressor cells (MDSCs) regulate castration resistance in PCa. Previously, it was shown that intercellular communication was efficiently mediated by exosomes (Exos), but the role and the mechanism of MDSC-derived Exos in CRPC progression was unclear. METHODS: In this study, the circRNA expression profiles in PC3 cells treated with MDSC-Exo and control cells were investigated using a circRNA microarray. RESULTS: The data showed that circMID1 (hsa_circ_0007718) expression was elevated in PC3 cells treated with MDSC-Exo. Moreover, high circMID1 expression was found in PCa compared with benign prostatic hyperplasia (BPH) tissues and in CRPC patients compared with hormone sensitive prostate cancer (HSPC) patients. Further studies showed that MDSC-Exo accelerated PCa cell proliferation, migration, and invasion, while circMID1 deficiency inhibited MDSC-Exo-regulated CRPC progression in vitro and in vivo. Mechanistically, MDSC-derived exosomal S100A9 increased circMID1 expression to sponge miR-506-3p, leading to increased MID1 expression and accelerated tumor progression. CONCLUSION: Together, our results showed that a S100A9/circMID1/miR-506-3p/MID1 axis existed in MDSC-Exo-regulated CRPC progression, which provided novel insights into MDSC-Exo regulatory mechanisms in CRPC progression.
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Exossomos , MicroRNAs , Células Supressoras Mieloides , Neoplasias de Próstata Resistentes à Castração , Linhagem Celular Tumoral , Proliferação de Células/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Células Supressoras Mieloides/metabolismo , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , RNA Circular/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Bladder cancer (Bca) is the most common cancer in urinary system. Recent studies revealed that circular RNAs (circRNAs) play vital roles in the development and progression of cancers. circMBOAT2 serves as an oncogenic gene in various kinds of cancer, promoting cell growth and metastasis. Nevertheless, the biological function of circMBOAT2 in Bca has not been reported. METHODS: qRT-PCR was used to measure the mRNA, circRNA and miRNA expression levels in Bca tissues and cells. Loss-of function experiments were carried to investigate the effect of circMBOAT2 on cell proliferation and migration. Nuclear mass separation, RNA pull-down and dual-luciferase reporter were performed to the molecular mechanisms underlying the functions of circMBOAT2. RESULTS: In this research, we identified that circMBOAT2 expression was increased in Bca tissues and positively corelated with unfavorable prognosis. In vitro assay demonstrated that suppression of circMBOAT2 impaired the proliferation and migration of Bca cells. Mechanically, circMBOAT2 was predominantly spread in cytoplasm and it sponged miR-433-3p to strengthen CREB1 expression. CONCLUSION: Hence, our study suggested that circMBOAT2 may serve as an oncogene in the development and progression of Bca and it will be the novel tumor biomarker and therapeutic target for Bca.
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MicroRNAs/metabolismo , RNA Circular/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Circular/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
Adjuvant chemotherapy(AC) plays a substantial role in the treatment of locally advanced gastric cancer (LAGC), but the response remains poor. We aims to improve its efficacy in LAGC. Therefore, we identified the expression of eight genes closely associated with platinum and fluorouracil metabolism (RRM1, RRM2, RRM2B, POLH, DUT, TYMS, TYMP, MKI67) in the discovery cohort (N=291). And we further validated the findings in TCGA (N=279) and GEO. Overall survival (OS) was used as an endpoint. Univariate and multivariate Cox models were applied. A multivariate Cox regression model was simulated to predict the OS. In the discovery cohort, the univariate Cox model indicated that AC was beneficial to high-RRM1, high-DUT, low-RRM2, low-RRM2B, low-POLH, low-KI67, low-TYMS or low-TYMP patients, the results were validated in the TCGA cohort. The multivariate Cox model showed consistent results. Cumulative analysis indicated that patients with low C-Score respond poorly to the AC, whereas the high and medium C-Score patients significantly benefit from AC. A risk model based on the above variables successfully predicted the OS in both cohorts (AUC=0.75 and 0.67, respectively). Further validation in a panel of gastric cancer cell (GC) lines (N=37) indicated that C-Score is significantly associated with IC50 value to fluorouracil. Mutation profiling showed that C-Score was associated with the number and types of mutations. In conclusion, we successfully simulated a predictive signature for the efficacy of AC in LAGC patients and further explored the potential mechanisms. Our findings could promote precision medicine and improve the prognosis of LAGC patients.
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It has been reported that the two major types of RNA interference triggers, the classical Dicer-generated small RNAs (siRNAs), which function with all members of the Argonaute (Ago) protein family in mammals, and the Ago2-sliced small RNAs (sli-siRNAs), which function solely through Ago2, have similar potency in target cleavage and repression. Here, we show that sli-siRNAs are generally more potent than siRNAs in silencing mismatched targets. This phenomenon is usually more apparent in targets that have mismatched nucleotides in the 3' supplementary region than in targets with mismatches in the seed region. We demonstrate that Ago2 slicer activity is a major factor contributing to the greater silencing efficiency of sli-siRNA against mismatched targets and that participation of non-slicing Agos in silencing mismatched siRNA targets may dilute the slicing ability of Ago2. The difference in length of the mature guide RNA used in sli-RISCs and si-RISCs may also contribute to the observed difference in knockdown efficiency. Our data suggest that a sli-siRNA guide strand is likely to have substantially stronger off-target effects than a guide strand with the same sequence in a classical siRNA and that Dicer and non-slicing Agos may play pivotal roles in controlling siRNA target specificity.
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Pareamento Incorreto de Bases , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Animais , Proteínas Argonautas/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Células HEK293 , Humanos , Camundongos , MicroRNAs/química , MicroRNAs/metabolismo , Processamento Pós-Transcricional do RNA , RNA Interferente Pequeno/química , Complexo de Inativação Induzido por RNA/metabolismo , Ribonuclease III/metabolismoRESUMO
BACKGROUND: The plant Alisma plantago-aquatica Linnaeus, which is widely distributed in southwest of China, is the main material of traditional Chinese medicine "Zexie". It was used as folk medicine for immune-modulation, anti-tumor, anti-inflammatory and antibacterial. Previous chemical studies on A. plantago-aquatica reported the identification of triterpenes, diterpenes, sesquiterpenes, steroids, alkaloids and phenolic acid. Terpenes and phenolic acid were regard as major secondary metabolites from this medicine plant. RESULTS: A new phenolic acid, plantain A (1), along with four known compounds (2-5) were isolated and identified from A. plantago-aquatica by extensive chromatographic and spectrometric methods. In the present study, the levels of TNF-α, IL-1ß, COX-2, PEG2 and TGF-ß1 were increased in model group rats, whereas on treatment with the isolated compound (1 and 4) at 50 mg/kg, there was a significant decrease in the cytokine levels. Therefore, the anti-CNP effect of 1 and 4 may be related to their anti-inflammatory properties. CONCLUSIONS: A new phenolic acid and four known phenolic compounds were isolated from A. plantago-aquatica. Moreover, compounds 1 and 4 shows significant anti-chronic prostatitis activity in rats.
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BACKGROUND: Gastric Cancer is one of the most lethal malignancies worldwide. Gamma-glutamyl transpeptidase (GGT) is an enzyme mainly involved in cellular glutathione homeostasis. We aim to explore the clinical value of GGT in gastric cancer. RESULTS: Among 322 patients enrolled, 65/82 patients were determined as GGT positive in serum/tumor, respectively. High tumor GGT expression is significantly associated with lymph node metastasis, histological subtype, and Her2 expression. Kaplan-Meier curve shows that high tumor GGT patients have shorter overall survival (P log-rank=0.001) and progress-free survival (P log-rank =0.001). Patients with both high tumor and serum GGT have the poorest prognosis. The multivariable Cox analysis shows that the hazard ratio of overall survival for high tumor GGT is 1.69 (95% CI 1.19-2.37). High serum GGT is a poor prognostic factor in adjuvant chemotherapy hazard ratio=2.18, 95%CI (1.15-4.47). These findings were further validated in six online datasets. Gene Sets Enrichment Analysis showed that GGT promotes cancer progression through EMT, KRAS, SRC and PKCA pathways. METHODS: Tumor GGT and serum GGT levels were evaluated with immuno-histochemistry staining and enzymatic assay, respectively. Kaplan-Meier curve and Cox regression model were used to test the association between GGT and gastric cancer prognosis. Independent datasets from Gene Expression Omnibus and Gene Sets Enrichment Analysis were applied to validate the findings and explore the potential mechanisms. CONCLUSION: Both tumor GGT and serum GGT are poor prognostic factors in gastric cancer. Patients with high tumor and serum GGT levels require more intense treatment and follow-up.
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Biomarcadores Tumorais/metabolismo , Neoplasias Gástricas/diagnóstico , gama-Glutamiltransferase/metabolismo , Carcinogênese , Feminino , Glutationa/metabolismo , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , gama-Glutamiltransferase/genéticaRESUMO
To explore the role of miRNAs in colorectal cancers (CRC), we have deep sequenced 48 pairs of frozen CRC samples, of which 44 pairs produced high quality sequencing data. By using a combined approach of our bias reduction small RNA (smRNA) deep sequencing protocol and Illumina small RNA TruSeq method for sample bar coding, we have obtained data from samples of relatively large size with bias reduced digital profile results. This novel approach allowed us to validate many previously published results using various techniques to profile miRNAs in CRC tissues or cell lines and to characterize 'true' miRNA signatures highly expressed in colon/rectum (CR) or CRC tissues. According to our results, miR-21, a miRNA that is up-regulated in CRC, and miR-143, a miRNA that is down-regulated in CRC, are the two miRNAs that dominated the miRNA population in CR tissues, and probably are also the most important miRNAs in CRCs. These two miRNAs, together with the other eight miRNAs, miR-148a, -194, -192, 200b, -200c, -10b, -26a, and -145, with descending expressing levels, constituted the top 10 highly expressed miRNAs in CR/CRC. Using TaqMan miRNA qPCR, we detected the relative expression of some of the CRC miRNAs in 10 CRC cell lines, validated their dysregulation under cancer condition, and provided possible explanation for their dysregulation, which could be caused by APC, KRAS, or TP53 mutations. We believe these results will provide a new direction in future miRNA-related CRC development studies, and application of miRNAs in CRC diagnosis/prognosis, and therapy.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Ribonucleotide reductase (RR) is an essential enzyme involved in DNA synthesis. We hypothesized that RR subunit M2 (RRM2) might be a novel prognostic and predictive biomarker for estrogen receptor (ER)-negative breast cancers. METHODS: Individual and pooled survival analyses were conducted on six independent large-scale breast cancer microarray data sets; and findings were validated on a human breast tissue set (ZJU set). RESULTS: Gene set enrichment analysis revealed that RRM2-high breast cancers were significantly enriched for expression of gene sets that increased in proliferation, invasiveness, undifferentiation, embryonic stem/progenitor-like phenotypes, and poor patient survival (p < 0.01). Independent and pooled analyses verified that increased RRM2 mRNA levels were associated with poor patient outcome in a dose-dependent manner. The prognostic power of RRM2 mRNA was comparable to multiple gene signatures, and it was superior to TNM stage. In ER-negative breast cancers, RRM2 showed more prognostic power than that in ER-positive breast cancers. Further analysis indicated that RRM2 was a more accurate prognostic biomarker for ER-negative breast cancers than the pathoclinical indicators and uPA. A new RR inhibitor, COH29, could significantly enhance the chemosensitivity to doxorubicin in ER-negative MDA-MB-231 cells, but not in ER-positive MCF-7 cells. CONCLUSION: RRM2 appears to be a promising prognostic biomarker and therapeutic target for ER-negative breast cancer patients.
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Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Ribonucleosídeo Difosfato Redutase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Feminino , Humanos , Células MCF-7 , Pessoa de Meia-Idade , Prognóstico , Receptores de Estrogênio/metabolismo , Ribonucleosídeo Difosfato Redutase/metabolismo , Análise de Sobrevida , Adulto JovemRESUMO
The main purpose of this study is to investigate the interactions between Lin28 and Her2 in gastric cancer. Lin28 and Her2 expression were evaluated in surgically resected samples of 298 gastric cancer patients using immunohistochemical staining. The correlations between Lin28/Her2 expression and clinical variables were retrospectively analyzed. The mRNA level of LIN28 and HER2 was detected by reverse-transcriptase polymerase chain reaction. Among all gastric cancer patients, 33.9% (101/298) were determined as Her2-positive, and 43.0% (128/298) were defined as Lin28-positive. Lin28 was significantly associated with Her2, advanced tumor stage, lesion size, and Ki67 level (p<0.05 for each). Kaplan-Meier analysis illustrated that both Lin28 and Her2 are poor prognostic factors in gastric cancer; Lin28(+)/Her2(+) patients have the poorest survival (median survival = 17 months, p<0.01). Multivariate Cox analysis showed that Lin28 is a significant prognostic factor (hazard ratio (HR) = 1.79, 95% confidence interval (CI) 1.23-2.62). Further stratification analysis indicated that Lin28 may be a prognostic factor in chemotherapy. In vitro data on MKN-28 and MKN-45 cells showed that Lin28 can upregulate Her2 expression at translational level. Both Lin28 and Her2 are poor prognostic factors in gastric cancer. Lin28 may regulate Her2 post-transcriptionally in gastric cancer cells, which indicates it might be a potential target in the treatment of gastric cancer.
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Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a RNA/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Western Blotting , Proliferação de Células , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptor ErbB-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
PURPOSE: To investigate the prognostic significance of ribonucleotide reductase small subunit M2 (RRM2) in low- and intermediate-risk prostate cancer (PCa). MATERIALS AND METHODS: A retrospective outcome study was conducted on 164 eligible PCa samples from the City of Hope (n = 90) and the Taipei Medical University (n = 74). The RRM2 protein levels were detected by immunohistochemistry. Biochemical recurrence was assessed using Kaplan-Meier and Cox proportional hazard analyses. Cell invasion assays, Ras/Raf, and matrix metallopeptidase 9 activities were determined to evaluate the role of RRM2 on invasiveness of PCa. RESULTS: Expression of RRM2 was significantly increased in patients with higher Gleason score, who had advanced T stage, and who were margin/capsule positive (P<0.05). Analysis revealed that the expression of RRM2 positively associated with biochemical recurrence of PCa in the City of Hope set (hazard ratio = 5.26; 95% CI 1.50-24.71) and the Taipei Medical University set (hazard ratio = 2.55; 95% CI 1.30-9.22). In stratification analysis, RRM2 was significantly correlated with poor outcome in patients with lower-risk PCa, including those with Gleason score 4 to 7, margin(-), capsule(-), and stage T1-T2. In patients with Gleason score 4 to 7, the risk of recurrence was proportional to RRM2 protein levels. The prognostic performance of RRM2 was superior to that of pathoclinical factors, including margin/capsule status and T stage. An in vitro study demonstrated that RRM2 could promote tumor invasion activities in PCa cell lines. Suppression of RRM2 reduced the Ras/Raf and matrix metallopeptidase 9 activities. CONCLUSION: RRM2 plays a critical role in proliferation and invasion of PCa. Adding RRM2 as a biomarker in clinical assessments may increase model precision in predicting recurrence in patients with low-risk PCa.