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Is PAWP the ＂real＂ sperm factor？

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Asian Journal of Andrology 2015年第3期17卷 444-446页

作者： Michail Nomikos Karl Swann f anthony lai Institute of Molecular and Experimental Medicine School of Medicine Cardiff University Cardiff UK

Mammalian embryo development is initiated by intracellular Ca2＋ oscillations that result in oocyte activation following gamete membrane fusion. It is widely believed that oocyte Ca2＋ oscillations are triggered by a sperm-specific protein, phospholipase C-zeta （PLCζ） that activates InsP3 production leading to repetitive Ca2. release from intracellular stores. However, a recent report in the fASEB Journal by Aarabi et al. challenges this view by proposing postacrosomal WW domain-binding protein （PAWP） as another sperm-derived protein that can also initiate Ca2＋ oscillations and zygotic development at fertilization. Here we discuss these new findings and examine the evidence suggesting PAWP as the ＂real＂ sperm factor.

关键词： PHOSPHOLIPASE-C-ZETA DOMAIN-BINDING-PROTEIN CA2+ OSCILLATIONS OOCYTE ACTIVATION EGG ACTIVATION CALCIUM OSCILLATIONS PLC-ZETA RELEASE fERTILIZATION INITIATE

Advancing male age differentially alters levels and localization patterns of PLCzeta in sperm and testes from different mouse strains

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Asian Journal of Andrology 2021年第2期23卷 178-187页

作者： Junaid Kashir Bhavesh V Mistry Maha Adel Gumssani Muhammad Rajab Reema Abu-Dawas falah AlMohanna Michail Nomikos Celine Jones Raed Abu-Dawud Nadya Al-Yacoub Kevin Coward f anthony lai Abdullah M Assiri College of Medicine Alfaisal UniversityRiyadh 11533Saudi Arabia Department of Comparative Medicine King Faisal Specialist Hospital and Research CentreRiyadh 11211Saudi Arabia College of Medicine QU HealthQatar UniversityDoha PO Box 2713Qatar Nuffield Department of Women’s and Reproductive Health University of OxfordLevel 3Women’s CentreJohn Radcliffe HospitalOxford OX39DUUnited Kingdom Biomedical Research Centre Qatar UniversityDoha PO Box 2713Qatar

Sperm-specific phospholipase C zeta(PLCζ)initiates intracellular calcium(Ca2+)transients which drive a series of concurrent events collectively termed oocyte *** investigations have linked abrogation and absence/reduction of PLCζwith forms of male infertility in humans where oocyte activation ***,very few studies have examined potential relationships between PLCζand advancing male age,both of which are increasingly considered to be major effectors of male *** efforts in humans may be hindered by inherent PLCζvariability within the human population,alongside a lack of sufficient controllable ***,utilizing immunoblotting,immunofluorescence,and quantitative reverse transcription PCR(qRT-PCR)we examined for the first time PLCζprotein levels and localization patterns in sperm,and PLCζmRNA levels within testes,from mice at 8 weeks,12 weeks,24 weeks,and 36 weeks of age,from two separate strains of mice,C57BL/6(B6;inbred)and CD1(outbred).Collectively,advancing male age generally diminished levels and variability of PLCζprotein and mRNA in sperm and testes,respectively,when both strains were ***,advancing male age altered the predominant pattern of PLCζlocalization in mouse sperm,with younger mice exhibiting predominantly post-acrosomal,and older mice exhibiting both post-acrosomal and acrosomal populations of PLCζ.However,the specific pattern of such decline in levels of protein and mRNA was ***,our results demonstrate a negative relationship between advancing male age and PLCζlevels and localization patterns,indicating that aging male mice from different strains may serve as useful models to investigate PLCζin cases of male infertility and subfertility in humans.

关键词： ageing fertilization male infertility oocyte activation phospholipase C zeta sperm

RyR受体二维阵列:美丽图案还是功能单位?

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RyR受体二维阵列:美丽图案还是功能单位?

第十次中国生物物理学术大会

作者：尹长城 f anthony lai 北京大学医学部生物物理学系 Wales Heart Research Institute Wales College of MedicineCardiff UniversityCardiff CF14 4XNUK

＜正＞Ryanodine受体（ryanodine receptor,RyR）是细胞内质网／肌质网上的一类快速释放Ca2+的通道,在细胞Ca2+信号转导相关的生理功能（如肌肉兴奋-收缩耦联）中起关键作用。在肌质网膜上,RyR分子排列成规则的美丽的二维阵列（two-dime...

＜正＞Ryanodine受体（ryanodine receptor,RyR）是细胞内质网／肌质网上的一类快速释放Ca2+的通道,在细胞Ca2+信号转导相关的生理功能（如肌肉兴奋-收缩耦联）中起关键作用。在肌质网膜上,RyR分子排列成规则的美丽的二维阵列（two-dimensional array）,类似于国际象棋盘,正方形的RyR分子以角对角的方式排列。尽管RyR分子

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过氧化氢调节RyR受体通道活性的分子基础

过氧化氢调节RyR受体通道活性的分子基础

Correlation and prognostic significance of beta-galactoside alpha-2,6-sialyltransferase and serum monosialylated alpha-fetoprotein in hepatocellular carcinoma

第十次中国生物物理学术大会

作者：韩红梅韦日生 f anthony lai 尹长城北京大学医学部生物物理学系北京大学医学部生物物理学系 Wales Heart Research Institute Wales College of MedicineCardiff UniversityCardiff CF14 4XNUK 北京大学医学部生物物理学系

＜正＞Ryanodine受体（ryanodine receptor,RyR）是细胞内质网／肌质网上的一类快速释放 Ca2+的通道,在细胞Ca2+信号转导相关的生理功能（如肌肉兴奋-收缩耦联）中起关键作用。RyR的功能受多种因子调节,如Ca2+、Mg2+、ATP、钙调蛋白、fK...

＜正＞Ryanodine受体（ryanodine receptor,RyR）是细胞内质网／肌质网上的一类快速释放 Ca2+的通道,在细胞Ca2+信号转导相关的生理功能（如肌肉兴奋-收缩耦联）中起关键作用。RyR的功能受多种因子调节,如Ca2+、Mg2+、ATP、钙调蛋白、fK-506结合蛋白、二氢嘧啶受体等。骨骼肌型RyR（RyR1）的每个亚单位含有100个半胱氨酸。有证据表明,一些半胱氨酸的氧化-还原状态参与调节RyR的功能。文献报导巯基修饰试剂, 如N-乙烯马来酰胺、二酰胺、谷胱甘肽、NOC-12、NO等可调节RyR的活性。但除了谷胱甘肽和NO,其它试剂为外源性物质,这些物质调节RyR的生理／病理意义有待进

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World Journal of Gastroenterology 2005年第42期11卷 6701-6706页

作者： Terence CW Poon Clarissa HS Chiu Paul BS lai Tony SK Mok Benny Zee anthony TC Chan Joseph JY Sung Philip J Johnson Department of Medicine and Therapeutics Sir YK Pao Cancer Centre the Chinese University of Hong Kong Prince of Wales Hospital NT Hong Kong China Department of Clinical Oncology Sir YK Pao Cancer Centre the Chinese University of Hong Kong Prince of Wales Hospital NT Hong Kong China Department of Surgery Sir YK Pao Cancer Centre the Chinese University of Hong Kong Prince of Wales Hospital NT Hong Kong China Cancer Research UK Institute for Cancer Studies University of Birmingham Vincent Drive Edgbaston Birmingham B15 2TT United Kingdom

AIM： To investigate the correlation between tissue ST6Gal I and serum msAfP in HCC patients, and to investigate their prognostic significance. METHODS： Preoperative sera, paired tumorous and non-tumorous tissues were collected from 19 consecutive patients who had undergone surgical resection of HCC. ST6Gal I activities in the tissues were measured by an in vitro microsomal enzyme activity assay. The percentages of tumor-specific msAfP in the sera were also estimated by an isoelectric focusing-immunoblotting assay. RESULTS： The tumor ST6Gal I activity was negatively correlated with serum msAfP percentage （r = -0.53, P = 0.019）. Both decreased tumor ST6Gal I activity and increased serum msAfP percentage were associated with poor tumor cell differentiation. Univariate analyses showed that both decreased tumor ST6Gal I activity （P = 0.028）, increased serum msAfP percentage （P = 0.034） and poor tumor cell differentiation （P = 0.031）were associated with shorter overall survival. Multivariate analysis using the Cox regression model showed that the preoperative serum msAfP percentage （P = 0.022） and tumor cell differentiation status （P = 0.048） were independent prognostic indicators for patient overall survival. CONCLUSION： Our results indicate that the presence of msAfP in blood circulation is associated with a decreased activity of ST6Gal I activity in HCC. Both tissue ST6Gal I and serum msAfP are potential prognostic markers for patients with operable HCC.

关键词： Alpha-fetoprotein Beta-galactoside alpha-2,6-sialyltransferase Hepatocellular carcinoma Patientsurvival Cell differentiation

Novel biomarkers GEP/ABCB5 regulate response to adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 524-530页

作者： Charing Ching-Ning Chong Siu Tim Cheung Yue-Sun Cheung anthony Wing-Hung Chan Stephen Lam Chan Simon Chun-Ho Yu Paul Bo-San lai Department of Surgery Prince of Wales HospitalThe Chinese University of Hong Kong4/F Clinical Science Building30-32 Ngan Shing StreetShatinHong KongChina Department of Anatomical and Cellular Pathology State Key Laboratory in Oncology in South ChinaPrince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina Department of Clinical Oncology Prince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina Department of Imaging and Interventional Radiology Prince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina

Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor(GEP) and ATP-dependent binding cassette(ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. Methods: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low(GEP-/ABCB5-), intermediate(either GEP +/ABCB5-or GEP-/ABCB5 +) and high(GEP +/ABCB5 +). Early recurrence(recurrence within 2 years after resection) and disease-free survival were analyzed. Results: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone( P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. Conclusions: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group(either GEP +/ABCB5-or GEP-/ABCB5 +). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.

关键词： Adjuvant therapy Hepatocellular carcinoma Drug transporter Transarterial chemoembolisation Granulin-epithelin precursor

International validation of the Chinese University Prognostic Index for staging of hepatocellular carcinoma: a joint United Kingdom and Hong Kong study

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Chinese Journal of Cancer 2014年第10期33卷 481-491页

作者： Stephen L.Chan Philip J.Johnson frankie Mo Sarah Berhane Mabel Teng anthony W.H.Chan Ming C.Poon Paul B.S.lai Simon Yu anthony T.C.Chan Winnie Yeo State Key Laboratory in Oncology in South China Sir YK Pao Center for CancerDepartment of Clinical OncologyHong Kong Cancer Institute and Prince of Wales HospitalThe Chinese University of Hong Kong School of Cancer Sciences University of Birmingham the Department of Molecular and Clinical Cancer Medicine Institute of Translational MedicineUniversity of Liverpool Department of Anatomical Cellular and PathologyThe Chinese University of Hong Kong Department of Surgery The Chinese University of Hong Kong Department of Radiology and Organ Imaging The Chinese University of Hong Kong

The outcome of hepatocellular carcinoma(HCC) patients significantly differs between western and eastern population centers. Our group previously developed and validated the Chinese University Prognostic Index(CUPI) for the prognostication of HCC among the Asian HCC patient population. In the current study, we aimed to validate the CUPI using an international cohort of patients with HCC and to compare the CUPI to two widely used staging systems, the Barcelona Clinic Liver Cancer(BCLC) classification and the Cancer of the Liver Italian Program(CLIP). To accomplish this goal, two cohorts of patients were enrolled in the United Kingdom(UK; n = 567; 2006-2011) and Hong Kong(HK; n = 517; 2007-2012). The baseline clinical data were recorded. The performances of the CUPI, BCLC, and CLIP were compared in terms of a concordance index(C-index) and were evaluated in subgroups of patients according to treatment intent. The results revealed that the median follow-up durations of the UK and HK cohorts were 27.9 and 29.8 months, respectively. The median overall survival of the UK and HK cohorts were 22.9 and 8.6 months, respectively. The CUPI stratified the patients in both cohorts into three risk subgroups corresponding to distinct outcomes. The median overall survival of the CUPI low-, intermediate-, and high-risk subgroups were 3.15, 1.24, and 0.29 years, respectively, in the UK cohort and were 2.07, 0.32, and 0.10 years, respectively, in the HK cohort. for the patients who underwent curative treatment, the prognostic performance did not differ between the three staging systems, and all were suboptimal. for those who underwent palliative treatment, the CUPI displayed the highest C-index, indicating that this staging system was the most informative for both cohorts. In conclusion, the CUPI is applicable to both western and eastern HCC patient populations. The performances of the three staging systems differed according to treatment intent, and the CUPI was demonstrated to be opti

关键词：香港英国预后肝癌验证国际大学中国

Robot-assisted minimally invasive procedures for complicated biliary stone disease

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Hepatobiliary Surgery and Nutrition 2018年第3期7卷 185-188页

作者： Kit fai Lee Andrew K. Y. fung Hon Ting Lok anthony K. W. fong Charing C. N. Chong Paul B. S. lai Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina

Introduction A big advancement in endoscopic management for biliary stone diseases was seen in the past three decades. Bile duct stones can be removed after sphincterotomy or balloon sphincteroplasty with stone basket... 详细信息

关键词： balloon biliary diseases

Pattern of disease recurrence and its implications for postoperative surveillance after curative hepatectomy for hepatocellular carcinoma: experience from a single center

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Hepatobiliary Surgery and Nutrition 2018年第5期7卷 320-330页

作者： Kit-fai Lee Charing C. N. Chong anthony K. W. fong Andrew K. Y. fung Hon-Ting Lok Yue-Sun Cheung John Wong Paul B. S. lai Department of Surgery Division of Hepatobiliary and Pancreatic Surgery Prince of Wales Hospital the Chinese University of Hong Kong Hong Kong China

Background: Hepatectomy is a widely accepted curative treatment for hepatocellular carcinoma (HCC). However, the disease frequently recurs after a curative hepatectomy. The objective of this study is to provide a better understanding of the pattern of disease recurrence and the risk factors involved so as to improve the postoperative surveillance. Methods: A retrospective study for all patients receiving hepatectomy for HCC between 2003 and 2014 was performed. Emphasis was made on the timing and pattern of recurrent disease, and type of treatment given. Results: There were 506 patients in the study. Median follow-up was 43.7 months. The 1-, 3-, 5-, 10-year overall and disease free survival were 89.5%, 74.1%, 63.9%, 49.0% and 69.5%, 54.3%, 43.4%, 30.9%respectively. Recurrent disease occurred in 267 patients, 47.2% occurred within 9 months of hepatectomy and 80.1% recurred only in liver. Median survival was shorter for recurrence occurring within 9 months compared with those occurring between 10 months and 2 years postoperatively (36.2 vs. 65.7 months, Pffered for patients with early (within 9 months) intrahepatic alone recurrence (22.2% vs. 51.7%, P3.5 cm and history of rupture were risk factors for recurrence within 9 months. Conclusions: These findings suggest that recurrent diseases are common after curative hepatectomy for HCC and most recurrences occur in the remnant liver. Since almost half of recurrences occurred within first 9 months after hepatectomy, a more stringent postoperative surveillance with target imaging of liver in this period is needed. Early diagnosis of recurrent disease and curative retreatment hopefully can bring about a longer survival.

关键词： Hepatectomy hepatocellular carcinoma (HCC) recurrence