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1.
Eur Urol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38692956

RESUMO

BACKGROUND: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤3 cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. INTERVENTION: Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. RESULTS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1-yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS: In patients with NMIBC of ≤3 cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR (funded by GRF/ECS, RGC, reference no.: 24116518; ClinicalTrials.gov number, NCT02993211). PATIENT SUMMARY: Conventionally, non-muscle-invasive bladder cancer is treated by resecting the bladder tumour in a piecemeal manner. In this study, we found that en bloc resection, that is, removal of the bladder tumour in one piece, could reduce the 1-yr recurrence rate of non-muscle-invasive bladder cancer.

2.
World J Urol ; 42(1): 97, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393414

RESUMO

BACKGROUND AND PURPOSE: This prospective study aimed to investigate adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (MRgSBRT) with rectal spacer for localized prostate cancer (PC) and report 1-year clinical outcomes. MATERIALS AND METHODS: Thirty-four consecutive patients with low- to high-risk localized PC that underwent 5-fraction adaptive MRgSBRT with rectal spacer were enrolled. The dosimetric comparison was performed on a risk- and age-matched cohort treated with MRgSBRT but without a spacer at a similar timepoint. Clinician-reported outcomes were based on Common Terminology Criteria for Adverse Events. Patient-reported outcomes were based on the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline, acute (1-3 months), subacute (4-12 months), and late (> 12 months) phases. RESULTS: The median follow-up was 390 days (range 28-823) and the median age was 70 years (range 58-82). One patient experienced rectal bleeding soon after spacer insertion that subsided before MRgSBRT. The median distance between the midline of the prostate midgland and the rectum after spacer insertion measured 7.8 mm (range 2.6-15.3), and the median length of the spacer was 45.9 mm (range 16.8-62.9) based on T2-weighted MR imaging. The use of spacer resulted in significant improvements in target coverage (V100% > 95% = 98.6% [range 93.4-99.8] for spacer vs. 97.8% [range 69.6-99.7] for non-spacer) and rectal sparing (V95% < 3 cc = 0.7 cc [range 0-4.6] for spacer vs. 4.9 cc [range 0-12.5] for non-spacer). Nine patients (26.5%) experienced grade 1 gastrointestinal toxicities, and no grade ≥ 2 toxicities were observed. During the 1-year follow-up period, EPIC scores for the bowel domain remained stable and were the highest among all other domains. CONCLUSIONS: MRgSBRT with rectal spacer for localized PC showed exceptional tolerability with minimal gastrointestinal toxicities and satisfactory patient-reported outcomes. Improvements in dosimetry, rectal sparing, and target coverage were achieved with a rectal spacer. Randomized trials are warranted for further validation.


Assuntos
Neoplasias da Próstata , Reto , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Prospectivos , Dosagem Radioterapêutica , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética
3.
Asian J Androl ; 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37695241

RESUMO

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance imaging. Men with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers (Queen Mary Hospital and Princess Margaret Hospital, Hong Kong, China) between January 2017 and June 2022 were included. Ultrasound-magnetic resonance imaging fusion biopsies were performed after prostate health index testing. Those who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were analyzed. Out of the 747 patients, 47.3% had Prostate Imaging Reporting and Data System score 3 lesions only. The detection rate of clinically significant prostate cancer in this group was 15.0%. The cancer detection rates of clinically significant prostate cancer had statistically significant differences: 5.3% in prostate health index <25.0, 7.4% in prostate health index 25.0-34.9, 17.9% in prostate health index 35.0-54.9, and 52.6% in prostate health index ≥55.0 (P < 0.01). Among the patients, 26.9% could have avoided a biopsy with a prostate health index <25.0, at the expense of a 5.3% risk of missing clinically significant prostate cancer. Prostate health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 lesions. Biopsies could be avoided in patients with low prostate health index, with a small risk of missing clinically significant prostate cancer.

4.
Front Cell Infect Microbiol ; 12: 936854, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237433

RESUMO

Background and objective: Urine culture is time consuming, which may take days to get the results and impede further timely treatment. Our objective is to evaluate whether the fast urinalysis and bacterial discrimination system called Sysmex UF-5000 may predict urinary tract infections (UTIs) (within minutes) compared with the clinical routine test in suspected UTI patients. In addition, we aimed to explore the accuracy of microbiologic information by UF-5000. Materials and Methods: Consecutive patients who were admitted from the emergency department at Queen Mary Hospital (a tertiary hospital in Hong Kong) from June 2019 to February 2020 were enrolled in the present study. The dipstick test, manual microscopic test with culture, and Sysmex UF-5000 test were performed in the urine samples at admission. Results: A total of 383 patients were finally included in the present study. UF-5000 urinalysis (area under the receiver operator characteristic curve, AUC=0.821, confidence interval, 95%CI: 0.767-0.874) outperformed the dipstick test (AUC=0.602, 95%CI: 0.550-0.654, P=1.32×10-10) for predicting UTIs in patients without prior antibiotic treatment. A significant net benefit from UF-5000 was observed compared with the dipstick test (NRI=39.9%, 95%CI: 19.4-60.4, P=1.36 × 10-4). The urine leukocyte tested by UF-5000 had similar performance (AUC) for predicting UTI compared with the manual microscopic test (P=0.27). In patients without a prior use of antibiotics, the concordance rates between UF-5000 and culture for predicting Gram-positive or -negative bacteriuria and a negative culture were 44.7% and 96.2%, respectively. Conclusions: UF-5000 urinalysis had a significantly better predictive value than the dipstick urine test for predicting UTIs.


Assuntos
Urinálise , Infecções Urinárias , Antibacterianos , Bactérias , Serviço Hospitalar de Emergência , Humanos , Sensibilidade e Especificidade , Urinálise/métodos , Infecções Urinárias/diagnóstico , Infecções Urinárias/microbiologia
5.
Cancer Res ; 82(5): 900-915, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34921016

RESUMO

The M2 pyruvate kinase (PKM2) isoform is upregulated in most cancers and plays a crucial role in regulation of the Warburg effect, which is characterized by the preference for aerobic glycolysis over oxidative phosphorylation for energy metabolism. PKM2 is an alternative-splice isoform of the PKM gene and is a potential therapeutic target. Antisense oligonucleotides (ASO) that switch PKM splicing from the cancer-associated PKM2 to the PKM1 isoform have been shown to induce apoptosis in cultured glioblastoma cells when delivered by lipofection. Here, we explore the potential of ASO-based PKM splice switching as a targeted therapy for liver cancer. A more potent lead constrained-ethyl (cEt)/DNA ASO induced PKM splice switching and inhibited the growth of cultured hepatocellular carcinoma (HCC) cells. This PKM isoform switch increased pyruvate-kinase activity and altered glucose metabolism. In an orthotopic HCC xenograft mouse model, the lead ASO and a second ASO targeting a nonoverlapping site inhibited tumor growth. Finally, in a genetic HCC mouse model, a surrogate mouse-specific ASO induced Pkm splice switching and inhibited tumorigenesis, without observable toxicity. These results lay the groundwork for a potential ASO-based splicing therapy for HCC. SIGNIFICANCE: Antisense oligonucleotides are used to induce a change in PKM isoform usage in hepatocellular carcinoma, reversing the Warburg effect and inhibiting tumorigenesis.


Assuntos
Processamento Alternativo , Carcinoma Hepatocelular , Neoplasias Hepáticas , Piruvato Quinase , Animais , Carcinogênese , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Glicólise/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Camundongos , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/farmacologia , Isoformas de Proteínas/genética , Piruvato Quinase/genética , Piruvato Quinase/metabolismo
6.
Asia Pac J Clin Oncol ; 17 Suppl 3: 48-54, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33860643

RESUMO

AIM: In response to the fast-developing coronavirus disease 2019 (COVID-19) pandemic, special arrangement and coordination are urgently required in the interdisciplinary care of patients across different medical specialties. This article provides recommendations on the management of different stages of localized or metastatic prostate cancer (PC) amid this pandemic. METHODS: The Hong Kong Urological Association and Hong Kong Society of Uro-oncology formed a joint discussion panel, which consisted of six urologists and six clinical oncologists with extensive experience in the public and private sectors. Following an evidence-based approach, the latest relevant publications were searched and reviewed, before proceeding to a structured discussion of relevant clinical issues. RESULTS: The joint panel provided recommendations for PC management during the pandemic, in terms of general considerations, diagnostic procedures, different disease stages, treatment modules, patient support, and interdisciplinary collaboration. The overall goal was to minimize the risk of infection while avoiding unnecessary delays and compromises in management outcomes. Practical issues during the pandemic were addressed such as the use of invasive diagnostic procedures, robotic-assisted laparoscopic prostatectomy, hypofractionated radiotherapy, and prolonged androgen deprivation therapy. The recommendations were explicated in the context of Hong Kong, a highly populated international city, in relation to the latest international guidelines and evidence. CONCLUSION: A range of recommendations on the management of PC patients during the COVID-19 pandemic was developed. Urologists, oncologists, and physicians treating PC patients may refer to them as practical guidance.


Assuntos
COVID-19/epidemiologia , Neoplasias da Próstata/terapia , SARS-CoV-2 , Antagonistas de Androgênios/uso terapêutico , Hong Kong/epidemiologia , Humanos , Masculino , Oncologia , Prostatectomia , Neoplasias da Próstata/patologia , Sociedades Médicas
7.
Asia Pac J Clin Oncol ; 17 Suppl 3: 12-26, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33860645

RESUMO

BACKGROUND: To update the Hong Kong Urological Association-Hong Kong Society of Uro-Oncology consensus statements on the management of advanced prostate cancer, the same panelists as in the previous consensus panel held a series of meetings to discuss updated clinical evidence and experiences. METHODS: The previous consensus statements were retained, deleted, or revised, and new statements were added. At the final meeting, all statements were reviewed and amended as appropriate, followed by panel voting. RESULTS: There were significant changes and additions to the previous consensus statements, primarily driven by the advances in androgen receptor signaling inhibitors, treatment sequencing in metastatic castration-resistant prostate cancer, and increasing recognition of oligometastatic prostate cancer since the introduction of prostate-specific membrane antigen positron emission tomography. In this update, a total of 59 consensus statements were accepted and established. CONCLUSIONS: The consensus panel updated consensus statements on the management of advanced prostate cancer, aiming to allow physicians in the region to keep abreast of the recent evidence on optimal clinical practices.


Assuntos
Neoplasias da Próstata/terapia , Urologia/métodos , História do Século XXI , Hong Kong , Humanos , Masculino , Neoplasias da Próstata/patologia
8.
Urol Case Rep ; 33: 101429, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33102125

RESUMO

External iliac artery dissection is a rare and under-reported vascular complication after renal transplantation. The etiology is yet to be fully understood. The presentation, investigation and management of this condition are highly variable. Here we report a 52-year-old man successfully treated by endovascular stenting with nitinol stents for an external iliac artery dissection proximal to the anastomosis.

9.
BJUI Compass ; 1(2): 74-81, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-35474710

RESUMO

Objectives: Cancer is the second leading cause of death globally in 2018 with an estimated 9.6 million deaths. The costs of managing malignant ureteric obstruction (MUO) is a significant burden to any healthcare system. However, the management of MUO has long been a challenge for urologists. The standard options of percutaneous nephrostomy or polymer double J stents are fraught with problems. We report a large patient series with long-term follow-up in the use of Resonance metallic ureteric stents to relieve MUO, and identification of risk factors associated with stent failure. Patients and methods: All patients with MUO who were arranged to have Resonance metallic ureteric stent insertion at two university hospitals were included in this cohort study, starting from June 2011 to July 2016. Data were retrieved retrospectively. The primary outcome was the total duration of stent patency before stent failure due to malignant disease progression. Stent failure was defined as ureteric obstruction identified on imaging (functional radioisotope scan or antegrade pyelogram), acute renal failure resolved by subsequent percutaneous nephrostomy, or any other cause requiring stent removal prematurely. Secondary outcomes were identification of factors associated with stent failure, grade III or above complication, and development of a risk-adopted model to predict metallic ureteric stent patency rates in MUO patients. Median duration of functioning metallic ureteric stent was determined with Kaplan-Meier survival curve. Results: A total of 124 renal units in 95 patients with MUO were eligible for the study, with a median follow-up period of 22.9 months. About 106 (85.5%) renal units had successful metallic stent insertion, of whom 41 (33.1%) renal units ultimately progressed to ureteric obstruction despite the metallic stents, and required subsequent insertion of nephrostomies. Median duration of functioning metallic ureteric stents was 25 months. Female gender (HR 3.0, 95% CI: 1.3-7.2, P = .014) and suspicious bladder lesion (HR 2.9, 95% CI: 1.4-6.2, P = .005) were independent risk factors for stent failure, respectively. Stratifying patients into low (0 risk factor), intermediate (1 risk factor), and high (2 risk factors) risk groups, we found that this could predict the duration of stent patency in MUO with the metallic stents. (Low risk: 30.3 months vs intermediate group: 17.8 months vs high risk: 4.9 months, P < .001). Conclusion: Resonance metallic ureteral stents are able provide a median of 25 months of ureteric drainage in patients with MUO. Determining whether a patient has one or both risks factors (female gender and bladder lesion) will allow one to estimate the duration of metallic stent patency, which in turn may aid in determining cost-effectiveness in individual patients.

10.
Nucleic Acids Res ; 48(2): 802-816, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31802121

RESUMO

Splice-switching antisense oligonucleotides (ASOs), which bind specific RNA-target sequences and modulate pre-mRNA splicing by sterically blocking the binding of splicing factors to the pre-mRNA, are a promising therapeutic modality to treat a range of genetic diseases. ASOs are typically 15-25 nt long and considered to be highly specific towards their intended target sequence, typically elements that control exon definition and/or splice-site recognition. However, whether or not splice-modulating ASOs also induce hybridization-dependent mis-splicing of unintended targets has not been systematically studied. Here, we tested the in vitro effects of splice-modulating ASOs on 108 potential off-targets predicted on the basis of sequence complementarity, and identified 17 mis-splicing events for one of the ASOs tested. Based on analysis of data from two overlapping ASO sequences, we conclude that off-target effects are difficult to predict, and the choice of ASO chemistry influences the extent of off-target activity. The off-target events caused by the uniformly modified ASOs tested in this study were significantly reduced with mixed-chemistry ASOs of the same sequence. Furthermore, using shorter ASOs, combining two ASOs, and delivering ASOs by free uptake also reduced off-target activity. Finally, ASOs with strategically placed mismatches can be used to reduce unwanted off-target splicing events.


Assuntos
Hibridização Genética , Oligonucleotídeos Antissenso/genética , Sítios de Splice de RNA/genética , Splicing de RNA/genética , Sítios de Ligação/genética , Linhagem Celular , Éxons/genética , Humanos , Hibridização de Ácido Nucleico/genética , Precursores de RNA/genética , RNA Mensageiro/genética
11.
Asia Pac J Clin Oncol ; 15 Suppl 6: 8-13, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31642191

RESUMO

AIM: The 2017 Advanced Prostate Cancer Consensus Conference (APCCC) convened an international multidisciplinary panel to vote on controversial issues in the management of advanced prostate cancer (APC). We aimed to compare their conclusions with the opinions of local specialists and explore the practicability of international recommendations in the healthcare setting in Hong Kong. METHODS: Urologists and clinical oncologists practicing in Hong Kong were invited to complete a survey based on the original APCCC 2017 questionnaire and recently published trials in APC. A joint committee of expert key opinion leaders was convened to discuss and analyze the voting differences between local specialists and the APCCC 2017 panel. RESULTS: The respondents constituted 21% (28/132) of registered urologists and 21% (31/146) of clinical oncologists in Hong Kong. Discrepancies in three key areas were identified as being the most timely for this analysis: (a) management of metastatic hormone-sensitive/naïve prostate cancer; (b) management of metastatic castration-resistant prostate cancer; and (c) treatment monitoring and initiation of androgen-deprivation therapy. Fears of toxicity and intolerance among patients and physicians (especially urologists) may be driving the relative underuse of chemotherapy in multiple APC patient groups in Hong Kong. Local patients can face long wait times and limited access to contemporary imaging modalities compared with other developed countries. CONCLUSION: Increased collaborative efforts by urologists and clinical oncologists could ensure that patients gain wider access to the latest diagnostic, treatment and monitoring modalities for APC in Hong Kong.


Assuntos
Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Neoplasias da Próstata/terapia , Inquéritos e Questionários , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/uso terapêutico , Terapia Combinada , Consenso , Gerenciamento Clínico , Hong Kong/epidemiologia , Humanos , Masculino , Prostatectomia , Neoplasias da Próstata/epidemiologia , Radioterapia
12.
Prostate Int ; 7(2): 73-77, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31384609

RESUMO

BACKGROUND: To investigate the role of Prostate Specific Antigen density (PSAD) in selecting prostate cancer patients for active surveillance (AS) and to determine a cutoff PSAD in identifying adverse pathological outcomes. METHODS: Data from 287 patients who underwent radical prostatectomy for prostate cancer were retrospectively reviewed. Six different AS protocols, the University of Toronto; Royal Marsden; John Hopkins; University of California San Francisco (UCSF); Memorial Sloan Kettering Cancer Center (MSKCC) and Prostate Cancer Research International: Active Surveillance (PRIAS), were applied to the cohort. Pre-operative demographics and pathological outcomes were analysed. Statistical analyses on the predictive factors of adverse pathological outcomes and significance of PSAD were performed. A cutoff PSAD with best balance between sensitivity and specificity in identifying adverse pathological outcome was determined. RESULTS: PSAD predicted adverse pathological outcomes better than Prostate Specific Antigen (PSA) level alone. The PSAD was significantly lower (0.12-0.13 ng/dl/ml) in protocols including PSAD (the John Hopkins and PRIAS) compared with the other four protocols not including PSAD as a selection criteria (0.21-0.25 ng/dl/dl, P = 0.00). PSAD predicted adverse pathological outcomes in all protocols not incorporating PSAD as an inclusion criteria (P = 0.00-0.02). By the receiver operator characteristics curve analysis, it was found that a PSAD level of 0.19 ng/ml/ml had the best balance between sensitivity and specificity in predicting pathological adverse disease (Area under curve = 0.63, P = 0.004). CONCLUSION: PSAD is necessary in selecting prostate cancer patients for active surveillance. It predicts adverse pathological outcomes in patients eligible for active surveillance better than PSA level alone. A PSAD cutoff at 0.19 ng/ml/ml has the best balance between sensitivity and specificity in predicting pathological adverse disease. We recommend using AS protocol incorporating PSAD as a selection criteria (in particular the PRIAS protocol with a cutoff PSAD at 0.2 ng/ml/ml) when recruiting prostate cancer patients for AS.

13.
BJU Int ; 124(2): 221-241, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30653801

RESUMO

OBJECTIVE: To formulate consensus statements to facilitate physician management strategies for patients with clinically localized prostate cancer (PCa) in Hong Kong by jointly convening a panel of 12 experts from the two local professional organizations representing PCa specialists, who had previously established consensus statements on the management of metastatic PCa for the locality. METHODS: Through a series of meetings, the panellists discussed their clinical experience and the published evidence regarding various areas of the management of localized PCa, then drafted consensus statements. At the final meeting, each drafted statement was voted on by every panellist based on its practicability of recommendation in the locality. RESULTS: A total of 76 consensus statements were ultimately accepted and established by panel voting. CONCLUSION: Derived from the recent evidence and major overseas guidelines, along with local clinical experience and practicability, the consensus statements were aimed to serve as a practical reference for physicians in Hong Kong for the management of localized PCa.


Assuntos
Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Consenso , Hong Kong , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem
14.
Wiley Interdiscip Rev RNA ; 10(2): e1519, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30506978

RESUMO

The mammalian DEAD-box RNA helicase DDX5, its paralog DDX17, and their orthologs in Saccharomyces cerevisiae and Drosophila melanogaster, namely Dbp2 and Rm62, define a subfamily of DEAD-box proteins. Members from this subfamily share highly conserved protein sequences and cellular functions. They are involved in multiple steps of RNA metabolism including mRNA processing, microRNA processing, ribosome biogenesis, RNA decay, and regulation of long noncoding RNA activities. The DDX5/Dbp2 subfamily is also implicated in transcription regulation, cellular signaling pathways, and energy metabolism. One emerging theme underlying the diverse cellular functions is that the DDX5/Dbp2 subfamily of DEAD-box helicases act as chaperones for complexes formed by RNA molecules and proteins (RNP) in vivo. This RNP chaperone activity governs the functions of various RNA species through their lifetime. Importantly, mammalian DDX5 and DDX17 are involved in cancer progression when overexpressed through alteration of transcription and signaling pathways, meaning that they are possible targets for cancer therapy. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.


Assuntos
RNA Helicases DEAD-box/metabolismo , RNA/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Animais , Humanos
15.
Genome Res ; 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29449409

RESUMO

Pre-mRNA splicing can contribute to the switch of cell identity that occurs in carcinogenesis. Here, we analyze a large collection of RNA-seq data sets and report that splicing changes in hepatocyte-specific enzymes, such as AFMID and KHK, are associated with HCC patients' survival and relapse. The switch of AFMID isoforms is an early event in HCC development and is associated with driver mutations in TP53 and ARID1A The switch of AFMID isoforms is human-specific and not detectable in other species, including primates. Finally, we show that overexpression of the full-length AFMID isoform leads to a higher NAD+ level, lower DNA-damage response, and slower cell growth in HepG2 cells. The integrative analysis uncovered a mechanistic link between splicing switches, de novo NAD+ biosynthesis, driver mutations, and HCC recurrence.

17.
BJU Int ; 121(5): 703-715, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29211320

RESUMO

To establish a set of consensus statements to facilitate physician management strategies for patients with metastatic prostate cancer (mPCa) in Hong Kong. A local expert consensus was organized jointly by the two main professional organizations representing prostate cancer specialists in Hong Kong. A total of 12 experts were included in the consensus panel. Six of the most crucial and relevant areas of debate regarding the management of mPCa were identified. With the use of a modified Delphi method, several panel meetings were held for the members to discuss their clinical experience and the published literature relevant to the areas of debate. At the final meeting, each drafted statement was voted on by every member based on its practicability of recommendation in the locality. After the panel voting, a total of 45 consensus statements regarding the management of mPCa were ultimately accepted and established. The consensus statements were primarily derived from the latest clinical evidence and major overseas guidelines, with the consideration of local clinical experience and practicability. These are considered applicable recommendations for Hong Kong physicians for the management of mPCa patients.


Assuntos
Metástase Neoplásica/patologia , Metástase Neoplásica/terapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Urologia , Inibidores da Angiogênese , Antineoplásicos , Biomarcadores Tumorais , Gerenciamento Clínico , Regulação Neoplásica da Expressão Gênica , Hong Kong , Humanos , Masculino , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Taxa de Sobrevida
18.
Aging Male ; 20(4): 241-249, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28787255

RESUMO

PURPOSE: To test the psychometric properties of the International Prostate Symptom Score (Hong Kong Chinese version 2) (IPSS) in Chinese male patients with benign prostatic hyperplasia (BPH) under secondary care. METHODS: A prospective longitudinal study was done by interviewing subjects at baseline, at 2 week after baseline for assessing test-retest reliability and at 26 week after baseline for assessing responsiveness. All subjects were interviewed to complete a structured questionnaire including IPSS, Short Form-12 Health Survey version 2 (SF-12v2) and Depression Anxiety Stress Scale (DASS). RESULTS: The IPSS HRQOL score had weak correlations with SF-12v2 summary and DASS domain scores. For reliability analysis, Cronbach's alpha coefficient was 0.90 for the seven symptom-related items. The intraclass correlation coefficients of the IPSS total symptom score and HRQOL score were 0.90 and 0.86, respectively. For sensitivity, statistically significant differences were detected between the subjects with BPH and those without for IPSS total symptom score (effect size = 0.68) but not the IPSS HRQOL score. The areas under ROC curves for the IPSS total symptom and HRQOL scores were 0.67 and 0.60, respectively. CONCLUSIONS: The IPSS was valid, reliable instrument in Chinese patients with BPH. The IPSS total symptom score, but not the HRQOL score, is sensitive in differentiating subgroups.


Assuntos
Inquéritos Epidemiológicos , Hiperplasia Prostática/psicologia , Qualidade de Vida , Idoso , Ansiedade/complicações , Estudos de Casos e Controles , Depressão/complicações , Hong Kong , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/fisiopatologia , Psicometria , Reprodutibilidade dos Testes , Estresse Psicológico/complicações
19.
Asian J Androl ; 19(1): 113-116, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-26620456

RESUMO

We investigated the performance characteristics of prostate-specific antigen (PSA) and PSA density (PSAD) in Chinese men. All Chinese men who underwent transrectal ultrasound-guided prostate biopsy (TRUS-PB) from year 2000 to 2013 were included. The receiver operating characteristic (ROC) curves for both PSA and PSAD were analyzed. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at different cut-off levels were calculated. A total of 2606 Chinese men were included. For the ROC, the area under curve was 0.770 for PSA (P < 0.001) and 0.823 for PSAD (P < 0.001). PSA of 4.5 ng ml-1 had sensitivity of 94.4%, specificity of 14.1%, PPV of 29.5%, and NPV of 86.9%; PSAD of 0.12 ng ml-1 cc-1 had sensitivity of 94.5%, specificity of 26.6%, PPV of 32.8%, and NPV of 92.7%. On multivariate logistic regression analyses, PSA cut-off at 4.5 ng ml-1 (OR 1.61, 95% CI 1.05-2.45, P= 0.029) and PSAD cut-off at 0.12 ng ml-1 cc-1 (OR 6.22, 95% CI 4.20-9.22, P< 0.001) were significant predictors for prostate cancer detection on TRUS-PB. In conclusion, the performances of PSA and PSAD at different cut-off levels in Chinese men were very different from those in Caucasians. PSA of 4.5 ng ml-1 and PSAD of 0.12 ng ml-1 cc-1 had near 95% sensitivity and were significant predictors of prostate cancer detection in Chinese men.


Assuntos
Calicreínas/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Área Sob a Curva , Povo Asiático , Biópsia com Agulha de Grande Calibre , China , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Curva ROC , Sensibilidade e Especificidade , Ultrassonografia
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