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BACKGROUND: The role of tumor inflammatory microenvironment in the advancement of cancer, particularly prostate cancer, is widely acknowledged. ELL-associated factor 2 (EAF2), a tumor suppressor that has been identified in the prostate, is often downregulated in prostate cancer. Earlier investigations have shown that mice with EAF2 gene knockout exhibited a substantial infiltration of inflammatory cells into the prostatic stroma. METHODS: A cohort comprising 38 patients who had been diagnosed with prostate cancer and subsequently undergone radical prostatectomy (RP) was selected. These patients were pathologically graded according to the Gleason scoring system and divided into two groups. The purpose of this selection was to investigate the potential correlation between EAF2 and CD163 using immunohistochemistry (IHC) staining. Additionally, in vitro experimentation was conducted to verify the relationship between EAF2 expression, macrophage migration and polarization. RESULTS: Our study demonstrated that in specimens of human prostate cancer, the expression of EAF2 was notably downregulated, and this decrease was inversely associated with the number of CD163-positive macrophages that infiltrated the cancerous tissue. Cell co-culture experiments revealed that the chemotactic effect of tumor cells towards macrophages was intensified and that macrophages differentiated into tumor-associated macrophages (TAMs) when EAF2 was knocked out. Additionally, the application of cytokine protein microarray showed that the expression of chemokine macrophage migration inhibitory factor (MIF) increased after EAF2 knockout. CONCLUSIONS: Our findings suggested that EAF2 was involved in the infiltration of CD163-positive macrophages in prostate cancer via MIF.
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Maize silk is a specialized type of stigma, covered with numerous papillae for pollen grain capture. However, the developmental process of stigmatic papillae and the underlying regulatory mechanisms have remained largely unknown. Here, we combined the cytological, genetic and molecular studies to demonstrate that three homologous genes ZmSPL10, ZmSPL14 and ZmSPL26 play a central role in promoting stigmatic papilla formation in maize. We show that their triple knockout mutants are nearly complete lack of stigmatic papilla, resulting in a severe reduction in kernel setting. Cellular examination reveals that stigmatic papilla is developed from a precursor cell, which is the smaller daughter cell resulting from asymmetric cell division of a silk epidermal cell. In situ hybridization shows that ZmSPL10, ZmSPL14 and their target genes SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A are preferentially expressed in the precursor cells of stigmatic papillae. Moreover, ZmSPL10, ZmSPL14 and ZmSPL26 directly bind to the promoters of SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A and promote their expression. Further, Zmwox3a knockout mutants display severe defects in stigmatic papilla formation and reduced seed setting. Collectively, our results demonstrate that ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla development through regulating auxin signaling and ZmWOX3A expression.
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Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos , Proteínas de Plantas , Transducción de Señal , Zea mays , Zea mays/genética , Zea mays/crecimiento & desarrollo , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutación/genética , Flores/genética , Flores/crecimiento & desarrollo , Regiones Promotoras Genéticas/genética , Genes de Plantas , Unión Proteica , FenotipoRESUMEN
Flowering time is a key agronomic trait determining environmental adaptation and yield potential of crops. The regulatory mechanisms of flowering in maize still remain rudimentary. In this study, we combine expressional, genetic, and molecular studies to identify two homologous SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors ZmSPL13 and ZmSPL29 as positive regulators of juvenile-to-adult vegetative transition and floral transition in maize. We show that both ZmSPL13 and ZmSPL29 are preferentially expressed in leaf phloem, vegetative and reproductive meristem. We show that vegetative phase change and flowering time are moderately delayed in the Zmspl13 and Zmspl29 single knockout mutants and more significantly delayed in the Zmspl13/29 double mutants. Consistently, the ZmSPL29 overexpression plants display precocious vegetative phase transition and floral transition, thus early flowering. We demonstrate that ZmSPL13 and ZmSPL29 directly upregulate the expression of ZmMIR172C and ZCN8 in the leaf, and of ZMM3 and ZMM4 in the shoot apical meristem, to induce juvenile-to-adult vegetative transition and floral transition. These findings establish a consecutive signaling cascade of the maize aging pathway by linking the miR156-SPL and the miR172-Gl15 regulatory modules and provide new targets for genetic improvement of flowering time in maize cultivars.
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Flores , Proteínas de Plantas , Proteínas de Plantas/metabolismo , Flores/fisiología , Zea mays/genética , Zea mays/metabolismo , Hojas de la Planta/metabolismo , Meristema/genética , Meristema/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Metastatic prostate cancer (mPCa) patients complicated with bladder outlet obstruction (BOO) are often referred to a urologist. Androgen deprivation therapy (ADT) combined with indwelling catheter usually be the initial management. To retrospectively analysis the safety and efficacy of simultaneous thulium laser resection of the prostate (TmLRP) and transperineal prostate biopsy in metastatic prostate cancer with bladder outlet obstruction. From January 2016 to December 2021, 67 clinically diagnosed mPCa with BOO patients were included in this study. All patients were preoperatively assessed with international prostate symptom score (IPSS), QoL, serum prostate-specific antigen (PSA), prostate volume evaluation by transrectal ultrasound, postvoid residual urine volume (PVR), and maximum flow rate (Qmax). Preoperative and perioperative parameters at 1-, 3-, and 6-month follow-up were also evaluated. All complications were recorded. Simultaneous TmLRP and transperineal prostate biopsy had obvious advantages for clinically diagnosed mPCa patients with BOO, including short overall operation time (52 ± 23.3 min), little hemoglobin decrease (0.6 ± 0.7 g/l), and short hospital stay (average 3.8 days). In addition, simultaneous TmLRP and transperineal prostate biopsy also brought them significant improvement on IPSS, QoL score, Qmax, and PVR volume (P < 0.001) at 1-, 3-, and 6-month follow-up after operation compared to preoperative parameters. Complications were in a low incidence. Simultaneous TmLRP and transperineal prostate biopsy is a bloodless operation with immediate effect and little perioperative complication. Importantly, it is a promising technology in the diagnosis and treatment of clinically diagnosed mPCa patients with BOO.
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Neoplasias de la Próstata , Obstrucción del Cuello de la Vejiga Urinaria , Masculino , Humanos , Próstata/cirugía , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/cirugía , Tulio , Antagonistas de Andrógenos , Calidad de Vida , Estudios Retrospectivos , Obstrucción del Cuello de la Vejiga Urinaria/diagnóstico , Obstrucción del Cuello de la Vejiga Urinaria/etiología , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Biopsia , Rayos LáserRESUMEN
OBJECTIVE: To explore the effect of a novel transurethral thulium laser vapoenucleation of the prostate with low-power conventional pulse mode (LP-ThuVEP) on sexual function in patients with benign prostatic hyperplasia (BPH). METHODS: 89 BPH patients admitted to Department of Urology, Jintan People's Hospital, Affiliated to Jiangsu University, from January 2022 to June 2023 were selected and randomly divided into the LP-ThuLEP group (45 cases) and the transurethral plasma kinetic resection of the prostate (TUPKRP) group (44 cases). Perioperative indicators were recorded, and the IPSS, Qmax, Qavg, PVR, and QoL of the two groups of patients before surgery and 3 months and 6 months after surgery were comparatively analyzed. The effect of surgery on male sexual function was evaluated through the International Index of Erectile Function-5 (IIEF-5) score and the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) score. RESULTS: Compared with the TUPKRP group, the LP-ThuVEP group had no statistically significant difference in operation time (P>0.05), but there were statistical differences in bladder irrigation time and indwelling urinary catheter time (P<0.05) and significant statistical differences in the decrease in hemoglobin on the day of surgery and the disappearance time of gross hematuria induced by defecation after surgery (P<0.001). The perioperative complications of the two groups were comparable. Among the urinary tract symptom indicators, the LP-ThuVEP group had statistically significant differences in IPSS score, QoL score, and PVR compared with the TUPKRP group 3 months after surgery (P<0.05). In terms of male sexual function, there was a statistical difference in IIEF-5 scores between the two groups at 3 months and 6 months after surgery (P<0.05); Except that there was no statistical difference in the ejaculation-related satisfaction scores between the two groups at 3 months after surgery (P>0.05), there had all significant statistical differences in ejaculation function and satisfaction scores between and within the groups at 3 months and 6 months after surgery (P<0.001). CONCLUSION: Compared with TUPKRP, the LP-ThuVEP can also effectively relieve urinary tract obstruction caused by BPH and has the advantages of less damage and faster recovery of erectile function and ejaculatory function of patients.
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Disfunción Eréctil , Terapia por Láser , Hiperplasia Prostática , Resección Transuretral de la Próstata , Humanos , Masculino , Próstata/cirugía , Hiperplasia Prostática/cirugía , Disfunción Eréctil/cirugía , Calidad de Vida , Resultado del TratamientoRESUMEN
The epidermal hair and stomata are two types of specialized structures on the surface of plant leaves. On mature maize leaves, stomatal complexes and three types of hairs are distributed in a stereotyped pattern on the adaxial epidermis. However, the spatiotemporal relationship between epidermal hair and stomata development and the regulatory mechanisms governing their formation in maize remain largely unknown. Here, we report that three homologous ZmSPL transcription factors, ZmSPL10, ZmSPL14 and ZmSPL26, act in concert to promote epidermal hair fate on maize leaf. Cytological analyses revealed that Zmspl10/14/26 triple mutants are completely glabrous, but possess ectopic stomatal files. Strikingly, the precursor cells for prickle and bicellular hairs are transdifferentiated into ectopic stomatal complexes in the Zmspl10/14/26 mutants. Molecular analyses demonstrated that ZmSPL10/14/26 bind directly to the promoter of a WUSCHEL-related homeobox gene, ZmWOX3A, and upregulate its expression in the hair precursor cells. Moreover, several auxin-related genes are downregulated in the Zmspl10/14/26 triple mutants. Our results suggest that ZmSPL10/14/26 play a key role in promoting epidermal hair fate on maize leaves, possibly through regulating ZmWOX3A and auxin-related gene expression, and that the fates of epidermal hairs and stomata are switchable.
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Hojas de la Planta , Zea mays , Diferenciación Celular , Epidermis , Factores de Transcripción/genética , Zea mays/genéticaRESUMEN
Phytohormones play important roles in regulating various aspects of plant growth and development as well as in biotic and abiotic stress responses. Stomata are openings on the surface of land plants that control gas exchange with the environment. Accumulating evidence shows that various phytohormones, including abscisic acid, jasmonic acid, brassinosteroids, auxin, cytokinin, ethylene, and gibberellic acid, play many roles in the regulation of stomatal development and patterning, and that the cotyledons/leaves and hypocotyls/stems of Arabidopsis exhibit differential responsiveness to phytohormones. In this review, we first discuss the shared regulatory mechanisms controlling stomatal development and patterning in Arabidopsis cotyledons and hypocotyls and those that are distinct. We then summarize current knowledge of how distinct hormonal signaling circuits are integrated into the core stomatal development pathways and how different phytohormones crosstalk to tailor stomatal density and spacing patterns. Knowledge obtained from Arabidopsis may pave the way for future research to elucidate the effects of phytohormones in regulating stomatal development and patterning in cereal grasses for the purpose of increasing crop adaptive responses.
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Proteínas de Arabidopsis , Arabidopsis , Reguladores del Crecimiento de las Plantas/fisiología , Estomas de Plantas/fisiología , Ácido Abscísico , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Arabidopsis/fisiología , Citocininas , Regulación de la Expresión Génica de las PlantasRESUMEN
Thulium laser resection of the prostate (TmLRP), a major treatment for benign prostatic hyperplasia (BPH), has several postoperative complications that affect the patients' quality of life. The aim of this study was to investigate the effect of the M1 macrophage-secreted reactive oxygen species (ROS) on prostatic wound healing, and the role of MAPK signaling in this process. A co-culture model in vitro was established using macrophages and prostate epithelial or stromal cells. Cell proliferation, migration, apoptosis, MAPK pathway-related gene expression levels were evaluated by standard assays. In addition, an in vivo model of prostatectomy was established in beagles by subjecting them to TmLRP, and were either treated with N-acetyl-L-cysteine (NAC) and or placebo. Wound healing and re-epithelialization were analyzed histopathologically in both groups, in addition to macrophage polarization, oxidative stress levels and MAPK pathway-related proteins expressions. Intracellular ROS levels were significantly increased in the prostate epithelial and stromal cells following co-culture with M1-like macrophages and H2O2 exposure via MAPK activation, which affected their proliferation, migration and apoptosis, and delayed the wound healing process. The cellular functions and wound healing capacity of the prostate cells were restored by blocking or clearing the macrophage-secreted ROS. In the beagle model, increased ROS levels impaired cellular functions, and appropriate removing ROS accelerated the wound healing process.
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Terapia por Láser , Macrófagos/enzimología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Estrés Oxidativo , Próstata/cirugía , Especies Reactivas de Oxígeno/metabolismo , Cicatrización de Heridas , Animales , Antioxidantes/farmacología , Apoptosis , Movimiento Celular , Proliferación Celular , Técnicas de Cocultivo , Perros , Células Epiteliales/enzimología , Células Epiteliales/patología , Transición Epitelial-Mesenquimal , Humanos , Terapia por Láser/instrumentación , Rayos Láser , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacos , Fenotipo , Próstata/enzimología , Próstata/patología , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal , Células del Estroma/enzimología , Células del Estroma/patología , Células THP-1 , Tulio , Factores de Tiempo , Cicatrización de Heridas/efectos de los fármacosRESUMEN
PURPOSE: To compare the safety and efficacy of thulium laser enucleation of the prostate (ThuLEP) versus thulium laser resection of the prostate (TmLRP) in small prostates (≤ 30 g) and to test the validity of ThuLEP for bladder neck contracture (BNC). METHODS: A total of 115 patients with benign prostatic hyperplasia (BPH) (prostate size ≤ 30 g) were randomly assigned to ThuLEP (n = 56) or TmLRP (n = 59). All patients were evaluated preoperatively and at 1, 3, 6, and 12 months after surgery. Baseline characteristics of the patients, perioperative data, postoperative outcomes and complications were assessed. RESULTS: Comparisons of the baseline and perioperative data demonstrated no significant differences between the ThuLEP and TmLRP groups. Significant improvement was noted in the International Prostate Symptom Score, quality of life, maximal urinary flow rate (Qmax) and post-void residual volume (PVR) in both groups at the 12-month follow-up, and assessment showed no differences in these parameters between the two groups. The TmLRP group showed a significantly higher rate (13.6%) of BNC than the ThuLEP group (1.8%; P = 0.045). There were no significant differences in other complications between the two groups (P > 0.05). CONCLUSIONS: ThuLEP and TmLRP are both safe and efficient procedures for the treatment of patients with small prostate volume, while ThuLEP can significantly reduce the risk of BNC in patients with a small prostate because the procedure enucleates adenomas without thermal damage to the bladder neck.
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Contractura/epidemiología , Terapia por Láser/métodos , Complicaciones Posoperatorias/epidemiología , Prostatectomía/métodos , Hiperplasia Prostática/cirugía , Obstrucción del Cuello de la Vejiga Urinaria/epidemiología , Anciano , Anciano de 80 o más Años , Humanos , Láseres de Estado Sólido , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Elongation factor for RNA polymerase 2 (ELL2) and ELL associated factor 2 (EAF2) have been reported to have tumor suppressive properties in prostate epithelial cells. AIMS: We investigated ELL2 expression in human prostate cancer specimens, and ELL2 protein stability and ubiquitination in prostate cancer cells. MATERIALS AND METHODS: Immunostaining analysis of human prostate cancer specimens was used to determine ELL2 expression in tumor and normal tissues. ELL2 knockdown in prostate cancer cell lines LNCaP and C4-2 was used to compare proliferation and motility. Deletion and site-directed mutagenesis was used to identify amino acid residues in ELL2 that were important for degradation. RESULTS: ELL2 protein was downregulated in prostate cancer specimens and was up-regulated by androgens in prostate cancer cell lines LNCaP and C4-2. ELL2 knockdown enhanced prostate cancer cell proliferation and motility. ELL2 protein has a short half-life and was stabilized by proteasome inhibitor MG132. Amino acid residues K584 and K599 in ELL2 were important for ELL2 degradation. EAF2 could stabilize ELL2 and inhibited its polyubiquitination. CONCLUSION: Our findings provide further evidence that ELL2 is a potential tumor suppressor frequently down-regulated in clinical prostate cancer specimens and provides new insights into regulation of ELL2 protein level by polyubiquitination and EAF2 binding.
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Neoplasias de la Próstata/metabolismo , Factores de Transcripción/metabolismo , Factores de Elongación Transcripcional/metabolismo , Andrógenos/metabolismo , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Leupeptinas/farmacología , Masculino , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/genética , Estabilidad Proteica , Factores de Elongación Transcripcional/biosíntesis , Factores de Elongación Transcripcional/genética , UbiquitinaciónRESUMEN
BACKGROUND: Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. METHODS: Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. RESULTS: The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. CONCLUSION: Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc.
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Andrógenos , Complicaciones Intraoperatorias , Próstata , Testosterona/análogos & derivados , Resección Transuretral de la Próstata/efectos adversos , Uretra , Andrógenos/administración & dosificación , Andrógenos/efectos adversos , Andrógenos/metabolismo , Animales , Modelos Animales de Enfermedad , Perros , Complicaciones Intraoperatorias/metabolismo , Complicaciones Intraoperatorias/fisiopatología , Complicaciones Intraoperatorias/terapia , Macrófagos/patología , Macrófagos/fisiología , Masculino , Próstata/patología , Próstata/cirugía , Repitelización/efectos de los fármacos , Repitelización/fisiología , Estadística como Asunto , Testosterona/administración & dosificación , Testosterona/efectos adversos , Testosterona/metabolismo , Tulio/farmacología , Resección Transuretral de la Próstata/métodos , Uretra/lesiones , Uretra/patología , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiologíaRESUMEN
Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer genesis and progression, including prostate cancer. Large amount of lncRNAs have been found that differentially expressed between prostate cancer tissues and normal prostate tissues. Whether these lncRNAs could serve as a novel biomarker for prostate cancer diagnosis or prognosis, and their biological functions in prostate cancer need further investigation. In the present study, we identified that lncRNA lnc-MX1-1 is over-expressed in prostate cancer tissues compared with their adjacent normal prostate tissues by gene expression array profiling. The expression of lnc-MX1-1 in 60 prostate cancer cases was determined by real-time quantitative PCR and the correlations between lnc-MX1-1 expression and patients' clinical features were further analyzed. Next, we impaired lnc-MX1-1 expression using RNAi in LNCaP and 22Rv1 prostate cancer cells to explore the effects of lnc-MX1-1 on proliferation and invasiveness of the cells. Our results showed that there was a significant association between over-expression of lnc-MX1-1 and patients' clinical features such as PSA, Gleason score, metastasis, and recurrence free survival. Moreover, knockdown of lnc-MX1-1 reduced both proliferation and invasiveness of LNCaP and 22Rv1 cells. In conclusion, the results suggest that lnc-MX1-1 may serve as a potential biomarker and therapeutic target for prostate cancer.
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Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , ARN Largo no Codificante/metabolismo , Proliferación Celular , Humanos , Masculino , Invasividad Neoplásica , Regulación hacia ArribaRESUMEN
BACKGROUND: ELL-associated factor 2 (EAF2) is an androgen-regulated tumor suppressor in the prostate. However, the mechanisms underlying tumor suppressive function of EAF2 are still largely unknown. Identification of factors capable of modulating EAF2 function will help elucidate the mechanisms underlying EAF2 tumor suppressive function. METHODS: Using eaf-1(the ortholog of EAF2) mutant C. elegans model, RNAi screen was used to identify factors on the basis of their knockdown to synergistically enhance the reduced fertility phenotype of the eaf-1 mutant C. elegans. In human cells, the interaction of EAF2 with FOXA1 and the effect of EAF2 on the FOXA1 protein levels were determined by co-immunoprecipitation and protein stability assay. The effect of EAF2 and/or FOXA1 knockdown on the expression of AR-target genes was determined by real-time RT-PCR and luciferase reporter assays. The effect of EAF2 and/or FOXA1 knockdown on LNCaP human prostate cancer cell proliferation and migration was tested using BrdU assay and transwell migration assay. RESULTS: RNAi screen identified pha-4, the C. elegans ortholog of mammalian FOXA1, on the basis of its knockdown to synergistically enhance the reduced fertility phenotype of the eaf-1 mutant C. elegans causing sterility. EAF2 co-immunoprecipitated with FOXA1. EAF2 knockdown enhanced endogenous FOXA1 protein level, whereas transfected GFP-EAF2 down-regulated the FOXA1 protein. Also, EAF2 knockdown enhanced the expression of AR-target genes, cell proliferation, and migration in LNCaP cells. However, FOXA1 knockdown inhibited the effect of EAF2 knockdown on AR-target gene expression, cell proliferation, and migration in LNCaP cells, suggesting that FOXA1 can modulate EAF2 regulation of AR transcriptional activation, cell proliferation, and migration. CONCLUSIONS: These findings suggest that regulation of the AR signaling pathway, cell proliferation, and migration through FOXA1 represents an important mechanism of EAF2 suppression of prostate carcinogenesis.
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Factor Nuclear 3-alfa del Hepatocito/metabolismo , Neoplasias de la Próstata/metabolismo , Receptores Androgénicos/metabolismo , Factores de Transcripción/metabolismo , Animales , Western Blotting , Caenorhabditis elegans , Línea Celular Tumoral , Proliferación Celular/fisiología , Regulación hacia Abajo , Factor Nuclear 3-alfa del Hepatocito/genética , Humanos , Inmunoprecipitación , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Interferencia de ARN/fisiología , Receptores Androgénicos/genética , Factores de Transcripción/genética , Activación Transcripcional , Transfección/métodosRESUMEN
PURPOSE: To evaluate the long-term durability and complication rates after thulium laser resection of prostate (TmLRP) through a prospective multiple-center study. MATERIALS AND METHODS: From November 2004 to December 2011, we prospectively studied 2,216 patients with symptomatic benign prostatic hyperplasia (BPH) treated with thulium laser resection of the prostate at four medical centers. Patients were assessed on International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), and postvoid residual urine (PVR). Perioperative complications were classified according to the modified Clavien classification system. RESULTS: Of 2,216 patients treated with TmLRP, 1,353 (61.1 %), 1,129 (50.9 %), 847 (38.2 %), and 541 (24.4 %) patients were followed at 5, 6, 7, and 8 years, respectively. Postoperatively, IPSS, QoL, Qmax, and PVR showed a significant improvement from 3 month after surgery and remained significantly improved during the entire follow-up period (p < 0.01). Minor complications occurred in 526 (23.7 %) of the 2,216 patients (Clavien 1: 21.5 %; Clavien 2: 2.3 %). Major complications requiring re-interventions occurred in 48 (2.2 %) of the 2,216 patients (Clavien 3: 2.2 %). No Clavien 4 or Clavien 5 complication had occurred. Urethral stricture and bladder neck contracture occurred in 2.6 % (58) and 1.6 % (35) patients, respectively. Persistent stress incontinence was found in 0.1 % (2) of the patients. Re-operation as a result of BPH recurrence was required in 1.2 % (27) patients. CONCLUSIONS: Thulium laser resection of the prostate is a safe and effective procedure with excellent durability in the treatment of symptomatic BPH.
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Láseres de Estado Sólido/uso terapéutico , Síntomas del Sistema Urinario Inferior/cirugía , Prostatectomía/métodos , Hiperplasia Prostática/cirugía , Tulio , Anciano , Humanos , Síntomas del Sistema Urinario Inferior/etiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Hiperplasia Prostática/complicaciones , Calidad de Vida , Reoperación , Resultado del TratamientoRESUMEN
PURPOSE: To assess the efficacy of intra-arterial chemotherapy as a bladder-preservation treatment in patients with muscle-invasive bladder cancer (MIBC) following transurethral resection of bladder tumors (TURBT). MATERIALS AND METHODS: From 2005 June to 2012 November, 46 patients diagnosed with MIBC (clinical stage T2-T3N0M0) underwent three courses of cisplatin-based intra-arterial chemotherapy as a remedial approach for bladder preservation after TURBT. All patients also received intravesical instillation of chemotherapy as a maintenance strategy. RESULTS: All 46 patients completed the treatment with minor complications. The median follow-up time was 34.5 months (range, 8-87 months). Thirty-two patients (69.6%) demonstrated complete response. The three-year and five-year overall survival was 70.65 and 61.23%, and the disease-specific survival over the same periods was 78.03 and 67.62%, respectively. During the entire follow-up period, more than 80% preserved their bladder. CONCLUSIONS: Intra-arterial chemotherapy can be performed as a remedial treatment for MIBC patient following TURBT. Combined with TURBT, it offers an option for bladder preservation therapy on patients who are unable or unwilling to undergo radical cystectomy.
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Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Cistectomía/métodos , Tratamientos Conservadores del Órgano/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Administración Intravesical , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Quimioterapia Adyuvante , Cisplatino/efectos adversos , Cistectomía/efectos adversos , Cistectomía/mortalidad , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Intraarteriales , Estimación de Kaplan-Meier , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Tratamientos Conservadores del Órgano/efectos adversos , Tratamientos Conservadores del Órgano/mortalidad , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: The function and significance of estrogen receptor ß (ERß) in bladder cancer remains a field of hot debate. In this study, we aimed to (a) evaluate ERß as a novel prognostic marker of recurrence free survival; and (b) digest the underlying mechanism by elucidating the relationship between ERß expression and cadherin switch. METHODS: We examined the expression levels of ERß, E-cadherin and N-cadherin in 42 initial non-muscle-invasive urothelial bladder carcinomas via immunohistochemistry. Correlation analysis was performed among ERß expression, cadherin switch and recurrence free survival. Moreover, in vitro studies were performed to validate the identified correlation using two bladder cancer cell lines RT4 and 253J. Upon stimulation with an ERß selective agonist diarylpropionitrile, E-cadherin, N-cadherin expressions; cell migration and invasion capacity were assessed. RESULTS: Expression of ERß protein was seen in 34 bladder cancer cases (80.9%), and 21 (50%) specimens showed non-cadherin switch (positive E-cadherin and negative N-cadherin). ERß expression and the non-cadherin switch are both accompanied with better recurrence free survival. Also, the least ERß expression was observed in specimens that undergo cadherin switch. Moreover, these results were consistent with our observations in bladder cancer RT4 and 253J cell lines studies. Diarylpropionitrile stimulation resulted in an increase in E-cadherin, a decrease in N-cadherin expression and abolished cell migration and invasion. CONCLUSION: ERß is a prognostic marker of recurrence free rate in non-muscle-invasive bladder cancer, potentially through suppressing cadherin switch, and may act as a potential target for bladder cancer therapy.
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Biomarcadores de Tumor/metabolismo , Cadherinas/metabolismo , Carcinoma de Células Transicionales/mortalidad , Receptor beta de Estrógeno/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Neoplasias de la Vejiga Urinaria/mortalidad , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Línea Celular Tumoral , Movimiento Celular , Terapia Combinada , Cistectomía , Quimioterapia , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Pronóstico , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To report the results of a randomized prospective trial with a 4-year follow-up, comparing the thulium laser resection of the prostate-tangerine technique (TmLRP-TT) with transurethral resection of prostate (TURP) for treatment of symptomatic benign prostatic hyperplasia (BPH). METHODS: BPH patients (96) were randomized for surgical treatment with TmLRP-TT (47) or TURP (49). All patients were assessed pre-operatively and followed at 12, 24, 36, and 48 months post-operatively. Several parameters related to BPH were collected at each follow-up, including International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rates (Qmax), and post-void residual volume (PVR). All late complications were also recorded. RESULTS: Dramatic improvement in micturition parameters was observed after TmLRP-TT compared with pre-operative values. Median IPSS decreased 75.6 % in the subsequent 12 months and 61.2 % in 48 months, while median QoL decreased by 80.4 and 59.1 %, respectively. Compared with baseline, numerical values of Qmax increased 1.07-fold and those of PVR decreased 73.1 % in the fourth year. Moreover, all micturition parameters in the TmLRP-TT group were similar to those of TURP patients at every annual assessment. Some late complications after the operations were also observed: one patient suffered from urethral strictures and one from bladder-neck contractures after TmLRP-TT. Re-operation rates were equal in the two groups. CONCLUSIONS: Micturition remained stable after TmLRP-TT during the 4-year follow-up. Outcomes compared favourably with TURP, with lower peri-operative morbidity and equally low occurrence of late adverse effects. Thus, TmLRP-TT can be an available option for BPH patients, especially older, high-risk patients.
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Terapia por Láser/métodos , Láseres de Estado Sólido/uso terapéutico , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Hiperplasia Prostática/diagnóstico , Factores de Tiempo , Resultado del TratamientoRESUMEN
It is becoming increasingly clear that N6-methyladenosine (m6A) plays a key role in post-transcriptional modification of eukaryotic RNAs in cancer. The regulatory mechanism of m6A modifications in prostate cancer is still not completely elucidated. Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), an m6A reader, has been revealed to function as an oncogenic RNA-binding protein. However, its contribution to prostate cancer progression remains poorly understood. Here, we found that HNRNPA2B1 was highly overexpressed and correlated with a poor prognosis in prostate cancer. In vitro and in vivo functional experiments demonstrated that HNRNPA2B1 knockout impaired proliferation and metastasis of prostate cancer. Mechanistic studies indicated that HNRNPA2B1 interacted with primary miRNA-93 and promoted its processing by recruiting DiGeorge syndrome critical region gene 8 (DGCR8), a key subunit of the Microprocessor complex, in an METTL3-dependent mechanism, while HNRNPA2B1 knockout significantly restored miR-93-5p levels. HNRNPA2B1/miR-93-5p downregulated FERM domain-containing protein 6 (FRMD6), a cancer suppressor, and enhanced proliferation and metastasis in prostate cancer. In conclusion, our findings identified a novel oncogenic axis, HNRNPA2B1/miR-93-5p/FRMD6, that stimulates prostate cancer progression via an m6A-dependent manner.
RESUMEN
Benign prostatic hyperplasia (BPH) is a condition that becomes more common with age and manifests itself primarily as the expansion of the prostate and surrounding tissues. However, to date, the etiology of BPH remains unclear. In this respect, we performed single-cell RNA sequencing of prostate transition zone tissues from elderly individuals with different prostate volumes to reveal their distinct tissue microenvironment. Ultimately, we demonstrated that a reduced Treg/CD4+ T-cell ratio in the large-volume prostate and a relatively activated immune microenvironment were present, characterized partially by increased expression levels of granzymes, which may promote vascular growth and profibrotic processes and further exacerbate BPH progression. Consistently, we observed that the prostate gland of patients taking immunosuppressive drugs usually remained at a smaller volume. Furthermore, in mouse models, we confirmed that both suppression of the immune system with rapamycin and induction of Treg proliferation with low doses of IL-2 therapy indeed prevented the progression of BPH. Taken together, our findings suggest that an activated immune microenvironment is necessary for prostate volume growth and that Tregs can reverse this immune activation state, thereby inhibiting the progression of BPH.
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Hiperplasia Prostática , Humanos , Masculino , Animales , Ratones , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Interleucina-2 , Sirolimus/farmacología , Sirolimus/uso terapéutico , Próstata/metabolismo , Modelos Animales de EnfermedadRESUMEN
Hybrid maize displays superior heterosis and contributes over 30% of total worldwide cereal production. However, the molecular mechanisms of heterosis remain obscure. Here we show that structural variants (SVs) between the parental lines have a predominant role underpinning maize heterosis. De novo assembly and analyses of 12 maize founder inbred lines (FILs) reveal abundant genetic variations among these FILs and, through expression quantitative trait loci and association analyses, we identify several SVs contributing to genomic and phenotypic differentiations of various heterotic groups. Using a set of 91 diallel-cross F1 hybrids, we found strong positive correlations between better-parent heterosis of the F1 hybrids and the numbers of SVs between the parental lines, providing concrete genomic support for a prevalent role of genetic complementation underlying heterosis. Further, we document evidence that SVs in both ZAR1 and ZmACO2 contribute to yield heterosis in an overdominance fashion. Our results should promote genomics-based breeding of hybrid maize.