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| 1 | siRNA therapeutics:a clinical reality显示文摘Since the revolutionary discovery of RNA interference(RNAi),a remarkable progress has been achieved in understanding and harnessing gene silencing mechanism;especially in small interfering RNA(siRNA)therapeutics.Despite its tremendous potential benefits,major challenges in most siRNA therapeutics remains unchanged-safe,efficient and target oriented delivery of siRNA.Twenty years after the discovery of RNAi,siRNA therapeutics finally charts its way into clinics.As we journey through the decades,we reminisce the history of siRNA discovery and its application in a myriad of disease treatments.Herein,we highlight the breakthroughs in si RNA therapeutics,with special feature on the first FDA approved RNAi therapeutics Onpattro(Patisiran)and the consideration of effective siRNA delivery system focusing on current siRNA nanocarrier in clinical trials.Lastly,we present some challenges and multiple barriers that are yet to be fully overcome in siRNA therapeutics. | Phei Er Saw Er-Wei Song | 2020 | Science China(Life Sciences)2020，63，4： | 26 |
| 2 | Non-coding RNAs:the new central dogma of cancer biology显示文摘The central dogma of molecular biology states that the functions of RNA revolve around protein translation.Until the last decade,most researches were geared towards characterization of RNAs as intermediaries in protein translation,namely,messenger RNAs(mRNAs)as temporary copies of genetic information,ribosomal RNAs(rRNAs)as a main component of ribosome,or translators of codon sequence(t RNAs).The statistical reality,however,is that these processes account for less than 2%of the genome,and insufficiently explain the functionality of 98%of transcribed RNAs.Recent discoveries have unveiled thousands of unique non-coding RNAs(ncRNAs)and shifted the perception of them from being'junk'transcriptional products to'yet to be elucidated'—and potentially monumentally important—RNAs.Most ncRNAs are now known as key regulators in various networks in which they could lead to specific cellular responses and fates.In major cancers,ncRNAs have been identified as both oncogenic drivers and tumor suppressors,indicating a complex regulatory network among these ncRNAs.Herein,we provide a comprehensive review of the various ncRNAs and their functional roles in cancer,and the pre-clinical and clinical development of nc RNA-based therapeutics.A deeper understanding of ncRNAs could facilitate better design of personalized therapeutics. | Phei Er Saw Xiaoding Xu Jianing Chen Er-Wei Song | 2021 | Science China(Life Sciences)2021，64，1： | 21 |
| 3 | Phage display screening of therapeutic peptide for cancer targeting and therapy显示文摘Recently,phage display technology has been announced as the recipient of Nobel Prize in Chemistry 2018.Phage display technique allows high affinity target-binding peptides to be selected from a complex mixture pool of billions of displayed peptides on phage in a combinatorial library and could be further enriched through the biopanning process;proving to be a powerful technique in the screening of peptide with high affinity and selectivity.In this review,we will first discuss the modifications in phage display techniques used to isolate various cancer-specific ligands by in situ,in vitro,in vivo,and ex vivo screening methods.We will then discuss prominent examples of solid tumor targeting-peptides;namely peptide targeting tumor vasculature,tumor microenvironment(TME)and overexpressed receptors on cancer cells identified through phage display screening.We will also discuss the current challenges and future outlook for targeting peptidebased therapeutics in the clinics. | Phei Er Saw Er-Wei Song | 2019 | Protein & Cell2019，10，11： | 11 |
| 4 | Chimeric antigen receptor T cells in solid tumors: a war against the tumor microenvironment显示文摘Chimeric antigen receptor(CAR) T cell is a novel approach, which utilizes anti-tumor immunity for cancer treatment. As compared to the traditional cell-mediated immunity, CAR-T possesses the improved specificity of tumor antigens and independent cytotoxicity from major histocompatibility complex molecules through a monoclonal antibody in addition to the Tcell receptor. CAR-T cell has proven its effectiveness, primarily in hematological malignancies, specifically where the CD19 CAR-T cells were used to treat B-cell acute lymphoblastic leukemia and B-cell lymphomas. Nevertheless, there is little progress in the treatment of solid tumors despite the fact that many CAR agents have been created to target tumor antigens such as CEA,EGFR/EGFRvIII, GD2, HER2, MSLN, MUC1, and other antigens. The main obstruction against the progress of research in solid tumors is the tumor microenvironment, in which several elements, such as poor locating ability, immunosuppressive cells,cytokines, chemokines, immunosuppressive checkpoints, inhibitory metabolic factors, tumor antigen loss, and antigen heterogeneity, could affect the potency of CAR-T cells. To overcome these hurdles, researchers have reconstructed the CAR-T cells in various ways. The purpose of this review is to summarize the current research in this field, analyze the mechanisms of the major barriers mentioned above, outline the main solutions, and discuss the outlook of this novel immunotherapeutic modality. | Zijun Zhao Xiaoyun Xiao Phei Er Saw Wei Wu Hongyan Huang Jiewen Chen Yan Nie | 2020 | Science China(Life Sciences)2020，63，2： | 7 |
| 5 | Challenges and strategies for next-generation bispecific antibody-based antitumor therapeutics显示文摘Bispecific antibodies(bsAbs)refer to a large family of molecules that recognize two different epitopes or antigens.Although a series of challenges,especially immunogenicity and chain mispairing issues,once hindered the development of bsAbs,they have been gradually overcome with the help of rapidly developing technologies in the past 5 decades.In the meantime,an increasing number of bsAb platforms have been designed to satisfy different clinical demands.Currently,numerous preclinical and clinical trials are underway,portraying a promising future for bsAb-based cancer treatment.Nevertheless,bsAb drugs still face enormous challenges in their application as cancer therapeutics,including tumor heterogeneity and mutational burden,intractable tumor microenvironment(TME),insufficient costimulatory signals to activate T cells,the necessity for continuous injection,fatal systemic side effects,and off-target toxicities to adjacent normal cells.Therefore,we provide several strategies as solutions to these issues,which comprise generating multispecific bsAbs,discovering neoantigens,combining bsAbs with other anticancer therapies,exploiting natural killer(NK)-cell-based bsAbs and producing bsAbs in situ.In this review,we mainly discuss previous and current challenges in bsAb development and underscore corresponding strategies,with a brief introduction of several typical bsAb formats. | Heliang Li Phei Er Saw Erwei Song | 2020 | Cellular & Molecular Immunology2020，17，5： | 6 |
| 6 | Effects of palbociclib on oral squamous cell carcinoma and the role of PIK3CA in conferring resistance显示文摘Objective: Lack of effective therapies remains a problem in the treatment of oral squamous cell carcinoma(OSCC), especially in patients with advanced tumors. OSCC development is driven by multiple aberrancies within the cell cycle pathway, including amplification of cyclin D1 and loss of p16. Hence, cell cycle inhibitors of the CDK4/6-cyclin D axis are appealing targets for OSCC treatment. Here, we determined the potency of palbociclib and identified genetic features that are associated with the response of palbociclib in OSCC.Methods: The effect of palbociclib was evaluated in a panel of well-characterized OSCC cell lines by cell proliferation assays and further confirmed by in vivo evaluation in xenograft models. PIK3CA-mutant isogenic cell lines were used to investigate the effect of PIK3CA mutation towards palbociclib response.Results: We demonstrated that 80% of OSCC cell lines are sensitive to palbociclib at sub-micromolar concentrations.Consistently, palbociclib was effective in controlling tumor growth in mice. We identified that palbociclib-resistant cells harbored mutations in PIK3CA. Using isogenic cell lines, we showed that PIK3CA mutant cells are less responsive to palbociclib as compared to wild-type cells with concurrent upregulation of CDK2 and cyclin E1 protein levels. We further demonstrated that the combination of a PI3 K/mTOR inhibitor(PF-04691502) and palbociclib completely controlled tumor growth in mice.Conclusions: This study demonstrated the potency of palbociclib in OSCC models and provides a rationale for the inclusion of PIK3CA testing in the clinical evaluation of CDK4/6 inhibitors and suggests combination approaches for further clinical studies. | Nur Syafinaz Zainal Bernard Kok Bang Lee Zheng Wei Wong Iuan Sheau Chin Pei San Yee Chai Phei Gan Kein Seong Mun Zainal Ariff Abdul Rahman J. Silvio Gutkind Vyomesh Patel Sok Ching Cheong | 2019 | Cancer Biology & Medicine2019，16，2： | 3 |
| 7 | Use of the transurethral prostatectomy clinical pathway to monitor health outcomes显示文摘 | Phei L Shih T Ming L | 1997 | The Journal of Urology1997，157，1： | 1 |
| 8 | Use of the transurethral prostat ectomy clinical path to moni-tor health outcomes显示文摘 | Phei Langchang Shih Tsunghuang Ming Lihsieh | 1997 | The Journal of Urology1997，157，1： | 1 |
| 9 | Use of the transurethral prostatectomy clinical path to monitor health outcomes显示文摘 | Phei Langchang Shih Tsunghuang Ming Lihsieh | 2012 | Journal of Urology2012，8，3： | 1 |
| 10 | Use of the transurethral prostatectomy clinical path to monitor health outcomes显示文摘 | Phei Langchang Shih Tsunghuang Ming Lihsieh | 1997 | The Journal of Urology1997，11，3： | 1 |
| 11 | Use of the transurethral prostatectomy clinical path to monitor health outcomes显示文摘 | PHEI LANGCHANG SHIH TSUNGHUANG MING LIHSIE | 1997 | The Journal of Urology1997，157，1： | 1 |
| 12 | The early effect of pelvic floor muscis exercise after transurethral prostatectomy显示文摘 | Phei LC Li HT Shih TH | 1998 | J Urol1998，160，2： | 1 |
| 13 | Metallothionein 3: An androgen‐upregulated gene enhances cell invasion and tumorigenesis of prostate carcinoma cells显示文摘 | Horng‐Heng Juang Li‐Chuan Chung Hsin‐Ching Sung Tsui‐Hsia Feng Yi‐Hua Lee Phei‐Lang Chang Ke‐Hung Tsui | 2013 | Prostate2013，，14： | 1 |
| 14 | THE EARLY EFFECT OF PELVIC FLOOR MUSCLE EXERCISE AFTER TRANSURETHRAL PROSTATECTOMY显示文摘 | PHEI LANG CHANG LI HUNY TSAI SHIH TSUNG HUANG TA MIN WANG MING LI HSIEH KE HUNG TSUI | 1998 | The Journal of Urology1998，，2： | 1 |
| 15 | Use of the transurethral prostatectomy clinical path to monitor health outcomes显示文摘 | Phei Langchang Shih Tsunghuang Ming Lihsieh | 1997 | The Journal of Urology1997，157，1： | 1 |
| 16 | Knowledge, Networks,and Knowledge Networks ; A Review and Research显示文摘 | PHEI PS C HEIDL R WADHWA A | 2012 | Journal of Management2012，38，4： | 1 |
| 17 | Use of the transurethral Proteetormy Clinical Path to monitor health outconges显示文摘 | Phei Langchang Shih Tsunghuang Ming lihsieh | | 0，，： | 1 |
| 18 | Use of the tran surethral prostatecto- myclinical path to monitor health outcomes 显示文摘 | Phei LC Shih TH Ming L | 1997 | The Journal of Urology1997，157，1： | 1 |
| 19 | Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer显示文摘Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma(HCC).Herein,RNAseq analysis revealed that elevated tubulin folding cofactor E(TBCE)expression is associated with platinum-based chemotherapy resistance.High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients.Mechanistically,TBCE silencing significantly affects cytoskeleton rearrangement,which in turn increases cisplatin-induced cycle arrest and apoptosis.To develop these findings into potential therapeutic drugs,endosomal pH-responsive nanoparticles(NPs)were developed to simultaneously encapsulate TBCE siRNA and cisplatin(DDP)to reverse this phenomena.NPs(siTBCE+DDP)concurrently silenced TBCE expression,increased cell sensitivity to platinum treatment,and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft(PDX)models.Taken together,NP-mediated delivery and the co-treatment of siTBCE+DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models. | Senlin Li Siyu Chen Zhihui Dong Xingdong Song Xiuling Li Ziqi Huang Huiru Li Linzhuo Huang Ganyuan Zhuang Ran Lan Mingyan Guo Wende Li Phei Er Saw Lei Zhang | 2023 | Acta Pharmaceutica Sinica B2023，13，3： | 1 |
| 20 | Use of the tran surethral prostatectomyclinical path to monitor health outcomes 显示文摘 | Phei Langchang Shih Tsunghuang Ming Lihsieh | 1997 | The Journal of Urology1997，157，1： | 1 |
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