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Can microfluidics address biomanufacturing challenges in drug/gene/cell therapies?

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Regenerative Biomaterials 2016年第2期3卷 87-98页

作者： hon Fai chan.Siying Ma Kam W.Leong Department of Biomedical Engineering Department of Systems BiologyColumbia UniversityNew YorkNY 10032USA

Translation of any inventions into products requires *** of drug/gene/cell delivery systems will eventually face manufacturing challenges,which require the establishment of standardized processes to produce biologically-relevant products of high quality without incurring prohibitive *** technologies present many advantages to improve the quality of drug/gene/cell delivery *** also offer the benefits of *** remains unclear is whether they can meet the scale-up *** this perspective,we discuss the advantages of microfluidic-assisted synthesis of nanoscale drug/gene delivery systems,formation of microscale drug/cell-encapsulated particles,generation of genetically engineered cells and fabrication of macroscale drug/cell-loaded micro-/*** also highlight the scale-up challenges one would face in adopting microfluidic technologies for the manufacturing of these therapeutic delivery systems.

关键词： microfluidics biomanufacturing nanoparticle microencapsulation microfiber

Management of thoracoabdominal neuroblastoma:a 13-year experience

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World Journal of Pediatric Surgery 2019年第2期2卷 47-52页

作者： Chan.hon.Chui Anselm Lee Surgery Centre for Children SingaporeSingapore Children's Haematology and Cancer Centre SingaporeSingapore

background Thoracoabdominal neuroblastoma is a unique surgical *** reviewed our experience focusing on disease patterns and corresponding surgical *** Among 310 patients in our neuroblastoma database,30(9.7%)had thoracoabdominal ***’clinical charts were reviewed and *** disease patterns were identified:solitary thoracoabdominal tumor(group A,n=15)and multifocal tumors in thorax and abdomen(group B,n=15).Operative approaches were categorized based on routes of surgical *** Thirty patients with average age of 4.1(range 0.8-12.8)years were *** received preoperative *** 15 group A patients,four were stage 3 intermediate risk(IR)and 11 were stage 4 high risk(HR).Surgical approaches included single-incision thoracoabdominal approach(n=10),laparotomy-cum-transdiaphragmatic approach(n=3),and laparotomy-cum-thoracotomy approach(n=2).One patient had 10%residual disease and the rest achieved gross total *** complications included chylous ascites(n=3),intestinal obstruction(n=3),pneumonia(n=1),spinal cord infarction(n=1)scoliosis(n=2)and thoracoabdominal nerves palsy(n=3).Among 15 group B patients,all were stage 4 with five IR and 10 *** components were found in the posterior mediastinum(n=7),superior mediastinum(n=4),middle mediastinum(n=1),parietal pleura(n=3)and lungs(n=3).Surgical approaches included multi-incision laparotomy-cum-thoracotomy(n=14)and laparotomy-cum-transdiaphragmatic approach(n=1).Gross total resection was achieved in all *** complications included chylous ascites(n=3).Overall,all nine IR patients survived without evidence of disease and 9(42.8%)HR patients died of *** was no perioperative *** Surgical resection of thoracoabdominal neuroblastoma is feasible and *** its complexity,thoracoabdominal neuroblastoma has comparable treatment outcomes when compared with single-compartmental disease

关键词： neuroblastoma abdominal chemotherapy

Hepatic adenoma mimicking a metastatic lesion on computed tomography-positron emission tomography scan

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World Journal of Gastroenterology 2013年第27期19卷 4432-4436页

作者： Darryl Lim Ser Yee Lee Kiat hon Lim Chung Yip chan Department of General Surgery Singapore General Hospital Department of Hepatopancreatobiliary and Transplant Surgery Singapore General Hospital Department of Surgical Oncology National Cancer Centre Duke-National University of Singapore (NUS) Graduate Medical School Department of Pathology Singapore General Hospital

Positron emission tomography (PET) using 18F-fluorodeoxyglucose ( 18F-FDG) is an imaging modality which reflects cellular glucose metabolism. Most malignant cells accumulate and trap 18F-FDG, allowing the visualisation of increased uptake. It is hence widely used to differentiate malignant from benign lesions. "False positive" findings of hepatic lesions have been described in certain instances such as hepatic abscesses, but are rare in cases involving hepatocellular adenomas. To our knowledge, there have been only 7 reports in the English literature documenting PET-avid hepatocellular adenomas; 6 of the 7 reports were published in the last 3 years with the first report by Patel et al. We report the case of a 44-year-old Chinese female patient with a history of cervical adenocarcinoma, referred for a hepatic lesion noted on a surveillance computed tomography (CT) scan. A subsequent CT-PET performed showed a hypermetabolic lesion (standardized uptake value 7.9) in segment Ⅳb of the liver. After discussion at a multidisciplinary hepato-pancreato-biliary conference, the consensus was that of a metastatic lesion from her previous cervical adenocarcinoma, and a resection of the hepatic lesion was performed. Histology revealed features consistent with a hepatocyte nuclear factor-1 α inactivated steatotic hepatocellular adenoma.

关键词： Hepatic adenoma Positron emission tomography 18F-fluorodeoxyglucose Hepatocellular adenoma Hepatocyte nuclear factor-1 α

Precision medicine in acute lymphoblastic leukemia

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Frontiers of Medicine 2020年第6期14卷 689-700页

作者： Ching-hon Pui Departments of Oncology and Pathology St.Jude Children’s Research HospitalMemphisTN 38105USA

The cure rate of childhood acute lymphoblastic leukemia(ALL)has exceeded 90%in some contemporary clinical ***,the dose intensity of conventional chemotherapy has been pushed to its *** improvement in outcome will need to rely more heavily on molecular therapeutic as well as immuno-and cellular-therapy approaches together with precise risk *** with ETV6-RUNX1 or hyperdiploid>50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in *** with Philadelphia chromosome(Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with ***3 profiling and other preclinical methods have identified several high-risk subtypes,such as hypodiplod,early T-cell precursor,immature T-cell,KMT2A-rearranged,Ph-positive and TCF-HLF-positive ALL,that may respond to BCL-2 inhibitor *** are other fusions or mutations that may serve as putative targets,but effective targeted therapy has yet to be *** other high-risk patients or poor early treatment responders who do not have targetable genetic lesions,current approaches that offer hope include blinatumomab,inotuzumab and CAR-T cell therapy for B-ALL,and daratumumab and nelarabine for *** the expanding therapeutic armamentarium,we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.

关键词： acute lymphoblastic leukemia molecular therapeutics targeted therapy tyrosine kinase inhibitors immunotherapy CAR T-cell therapy

一种计算机辅助设计数据文本服务程序的设计和实现

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软件 1989年第9期10卷 665-684页

作者： chan.,EE 邵惠玲

Flocking behavior of forest birds in hong Kong,South China

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Journal of Forestry Research 2017年第5期28卷 1097-1102页

作者： hon Kai Kwok Ecosystems Ltd

This paper reports observations of flocking behavior of birds in a well-protected secondary forest in Tai Po Kau Nature Reserve, hong Kong Special Administrative Region, China. A total of 1025 flocks including 5255 birds and 48 species were observed between October 2002 and November 2003. Most flocks consisted of only one species. The observed flocks averaged 1.79 +/- 0.05 (SE) species and 5.13 +/- 0.18 (SE) birds. The Japanese White-eye was the most numerous species and was present in 21.6% of the observed flocks. Seasonal trends in both flock size and number of species were similar to those in overall bird density and species richness in the study area reported in a previous study.

关键词： Forest bird Forest Flock Tai Po Kau Nature Reserve hong Kong special administrative region

Genomic and pharmacogenetic studies of childhood acute lymphoblastic leukemia

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Frontiers of Medicine 2015年第1期9卷 1-9页

作者： Ching-hon Pui Departments of Oncology and Pathology St. Jude Children's Research Hospital Memphis TN 38105 USA the University of Tennessee Health Science Center Memphis 7N 38105 USA

With the cure rate of childhood acute lymphoblastic leukemia （ALL） approaching 90%, further improvement in the treatment outcome and quality of life of patients will require better understanding of the mechan.sms of drug resistance, identifying new leukemic cell genetic lesions that are amendable to available target therapy, and optimizing treatment based on host pharmacodynamics and pharmacogenomics. Deeper characterization of leukemic cell genetic abnormalities has discovered new subtypes of leukemia such as early T-cell precursor ALL and Philadelphia chromosome-like ALL, and identified many genomic alterations that have diagnostic, prognostic, or therapeutic implications. In this regard, several novel fusion transcripts are responsive to ABL tyrosine kinase inhibitors and potentially to JAK inhibitors. Genome-wide analyses have also unraveled the role of inherited cancer predisposing genes and small nucleotide polymorphisms of several genes in the development of childhood ALL. These advances promise to lead to more sophisticated personalized treatment strategies in the near future.

关键词： acute lymphoblastic leukemia genomics pharmacogenetics pharmacogenomics

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OS／2EE数据库管理系统概要和技术要点

微型计算机 1989年第4期9卷 82-90页

作者： chan.,PY 曾庆辉

Cyclic ADP-ribose and NAADP:fraternal twin messengers for calcium signaling

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Science China(Life Sciences) 2011年第8期54卷 699-711页

作者： hon Cheung LEE Department of Physiology University of Hong Kong

The concept advanced by Berridge and colleagues that intracellular Ca2+-stores can be mobilized in an agonist-dependent and messenger(IP3)-mediated manner has put Ca 2+-mobilization at the center stage of signal transduction *** the late 1980s,we showed that Ca2+-stores can be mobilized by two other messengers unrelated to inositol trisphosphate(IP 3) and identified them as cyclic ADP-ribose(cADPR),a novel cyclic nucleotide from NAD,and nicotinic acid adenine dinucleotide phosphate(NAADP),a linear metabolite of *** messenger functions have now been documented in a wide range of systems spanning three biological *** evidence indicates that the target of cADPR is the ryanodine receptor in the sarco/endoplasmic reticulum,while that of NAADP is the two pore chan.el in endolysosomes. As cADPR and NAADP are structurally and functionally distinct,it is remarkable that they are synthesized by the same *** are thus fraternal twin *** first identified the Aplysia ADP-ribosyl cyclase as one such enzyme and,through homology,found its mammalian homolog,*** knockout in mice confirms the important roles of CD38 in diverse physiological functions from insulin secretion,susceptibility to bacterial infection,to social behavior of mice through modulating neuronal oxytocin *** have elucidated the catalytic mechan.sms of the Aplysia cyclase and CD38 to atomic resolution by crystallography and site-directed *** article gives a historical account of the cADPR/NAADP/CD38-signaling pathway and describes current efforts in elucidating the structure and function of its components.

关键词： cyclic ADP-ribose cADPR NAADP nicotinic acid adenine dinucleotide phosphate CD38 ADP-ribosyl cyclase Calcium mobilization and signaling