Shian-Ying Sung

• Doctor of Philosophy
• Professor (Associate) at Taipei Medical University

Advanced prostate cancer is distinguished by substantial heterogeneity and intricacy, which present challenges in devising effective treatment strategies. The genetic landscape of prostate cancer is frequently altered, contributing to the development of resistance to conventional therapies and exacerbating systemic toxicity. These challenges necess...

Atypical teratoid/rhabdoid tumors (ATRTs) are highly aggressive pediatric brain tumors with sensitivity to proteasome inhibitors in preclinical models. We evaluated the feasibility of combining the proteasome inhibitor bortezomib with chemotherapy. Patients aged 0-20 years with newly diagnosed ATRT were enrolled from January 2022 through December 2...

Bladder cancer treatments are highly aggressive and have strong side effects. Safer and more effective treatments are needed. In this study, Dibenzolium (DIB), a potent NADPH oxidase inhibitor, was evaluated for its anti-tumor effects. KK-47 (non-invasive), T24 and 5637 (invasive) cells were used in experiments. Cell proliferation, apoptosis and wo...

Background Atypical teratoid rhabdoid tumor (ATRT) is an aggressive brain tumor that mainly affects young children. Our recent study reported a promising therapeutic strategy to trigger DNA damage, impede homologous recombination repair, and induce apoptosis in ATRT cells by targeting ribonucleotide reductase regulatory subunit M2 (RRM2). COH29, an...

Background A specific type of prostate cancer (PC) that exhibits neuroendocrine (NE) differentiation is known as NEPC. NEPC has little to no response to androgen deprivation therapy and is associated with the development of metastatic castration‐resistant PC (CRPC), which has an extremely poor prognosis. Our understanding of genetic drivers and act...

Background Medulloblastomas (MBs) are one of the most common malignant brain tumor types in children. MB prognosis, despite improvement in recent years, still depends on clinical and biological risk factors. Metastasis is the leading cause of MB-related deaths, which highlights an unmet need for risk stratification and targeted therapy to improve c...

Background: Atypical teratoid rhabdoid tumors (ATRT) is a rare but aggressive malignancy in the central nervous system, predominantly occurring in early childhood. Despite aggressive treatment, the prognosis of ATRT patients remains poor. RRM2, a subunit of ribonucleotide reductase, has been reported as a biomarker for aggressiveness and poor progn...

Introduction: Medulloblastoma (MB) is the most common malignant tumor in children. Since most MB-related deaths are the result of metastasis, current standard care for MB is aggressive with intense post-surgical radiotherapies, which aim to minimize metastatic occurences and are applied in most cases regardless of tumor subgroups. Among the four mo...

The high metastasis and drug resistance of colorectal cancer (CRC) cause high mortality and rank third among the top ten cancer deaths. TY1 is a biflavonoid isolated from Taxus x media cv. Hicksii. We have previously reported that TY1 inhibits metastatic behavior by inhibiting F-actin polymerization. However, the biological activities of TY1 to ove...

Medulloblastoma (MB) was classified into four molecular subgroups: WNT, SHH, group 3, and group 4. In 2017, 12 subtypes within 4 subgroups and 8 subtypes within non-WNT/non-SHH subgroups according to the differences of clinical features and biology were announced. In this study, we aimed to identify the heterogeneity of molecular features for disco...

Background: Castration-resistant prostate cancer (PCa; CRPC) has a poor response to androgen deprivation therapy and is considered an incurable disease. MicroRNA (miR)-lethal 7c (let-7c) was implied to be a tumor suppressor in PCa, and treatment with exogenous let-7c targets both cancer cells and their associated mesenchymal stem cells (MSCs) to p...

Distant metastasis is the leading cause of death in patients with breast cancer. Despite considerable treatment advances, the clinical outcomes of patients with metastatic breast cancer remain poor. CSCs can self-renew, enhancing cancer progression and metastasis. Dicer, a microRNA (miRNA) processing-related enzyme, is required for miRNA maturation...

Background Hypermucoviscous (HMV) Klebsiella pneumoniae produces large amounts of capsular polysaccharides, leading to high mortality. Since extended spectrum beta-lactamase (ESBL)-producing HMV K. pneumoniae strains have increased in Japan, we investigated and compared the antimicrobial susceptibilities and genetic characteristics of HMV and non-H...

Klebsiella pneumoniae is a typical pathogen in urinary tract infections (UTI), and the emergence of extended spectrum beta-lactamase (ESBL)-producing strains has been frequently reported, accompanied by higher quinolone resistance rates. There are two major mechanisms of quinolone resistance, mutations in quinolone resistance-determining regions (Q...

Introduction: Medulloblastoma (MB) is the most common malignant tumor in children. MB-related treatment failures and deaths mostly result from metastasis. One of the key genetic drivers in MB is MYCN, whose aberrant expressions are associated with tumor aggressiveness and poor prognosis. Long non-coding (lnc)RNAs have been implied as potential targ...

Introduction: Cancer-associated fibroblasts (CAFs), the main cellular component of the tumor microenvironment (TME), contribute to tumor metastasis. Prostate cancer (PCa) is the most common malignancy among the elderly male population, and it is typically fatal when the disease progresses to metastasis and castration-resistant stage (CRPC). We have...

Introduction. Azithromycin (AZM) is a therapeutic drug for sexually transmitted infections and is used for Neisseria gonorrhoeae when first- and second-line drugs are not available. Recently, the susceptibility of N. gonorrhoeae against AZM has been decreasing worldwide. Hypothesis/Gap Statement. Azithromycin-resistance (AZM-R) rates among N. gonor...

We evaluated the effect of A Disintegrin and Metalloproteinase Domain-Containing (ADAM)9 protein on exacerbation in bladder cancer KK47 and T24. First, we knocked down ADAM9 and investigated cell proliferation, migration, cell cycle, and the epithelial–mesenchymal transition (EMT)-related proteins expression in vitro. We then investigated the expre...

Most cases of hepatocellular carcinoma (HCC) arise with the fibrotic microenvironment where hepatic stellate cells (HSCs) and carcinoma-associated fibroblasts (CAFs) are critical components in HCC progression. Therefore, CAF normalization could be a feasible therapy for HCC. Galectin-1 (Gal-1), a β-galactoside-binding lectin, is critical for HSC ac...

Medulloblastoma (MB) is the most common malignant brain tumor in children. It is classified into core molecular subgroups (non-wingless activated (WNT), sonic hedgehog activated (SHH), Group 3 (G3), and Group 4 (G4)). In this study, we analyzed the tumor-infiltrating immune cells and cytokine profiles of 70 MB patients in Taiwan using transcriptome...

Background: Ultrasound (US) is mostly used for diagnostic purpose but could be used for cancer treatments with a US intensity or frequency fitted to such a purpose. Prostate cancer (PC) has the highest prevalence in the urological field, but indications for immune checkpoint inhibitors (ICIs) for PC are limited to very few cases. In this study, we...

Metastatic and castration-resistant disease is a fatal manifestation of prostate cancer (PCa). The mechanism through which resistance to androgen deprivation in PCa is developed remains largely unknown. Our understanding of the tumor microenvironment (TME) and key signaling pathways between tumors and their TME is currently changing in light of the...

The number of syphilis patients has significantly increased recently in Japan and worldwide. Previous reports, even in large institutions, may not accurately reflect the current situation in urological clinics. We therefore collected data from 11 urological clinics in Hyogo Prefecture, Japan over a 2-year period subdivided into 1) August 2016 to Ju...

Imipenemase-6 (IMP-6) type carbapenemase-producing Enterobacteriaceae is regarded as dangerous due to its unique lack of antimicrobial susceptibility. It is resistant to meropenem (MEPM) but susceptible to imipenem (IPM). In addition to carbapenemase, outer membrane porins and efflux pumps also play roles in carbapenem resistance by reducing the an...

Abstract Medulloblastoma is the most common embryonic brain tumor in children. We investigated a cohort of 52 Asian medulloblastoma patients aged between 0 and 19 years old, who received surgical resections and post-resection treatments in the Taipei Medical University Hospital and the Taipei Veterans General Hospital. Genome-wide RNA sequencing wa...

Treating brain tumors presents enormous challenges, and there are still poor prognoses in both adults and children. Application of novel targets and potential drugs is hindered by the function of the blood-brain barrier, which significantly restricts therapeutic access to the tumor. Mesenchymal stem cells (MSCs) can cross biological barriers, migra...

p>Introduction: Castration-resistant prostate cancer (CRPC) has poor response to androgen deprivation therapy, which is caused by a sustained androgen receptor (AR) signal and therefore is considered as an incurable disease. MicroRNA let-7c has been implied as a tumor suppressor in prostate cancer by antagonizing AR expression and activity. In addi...

[This corrects the article DOI: 10.3389/fonc.2021.638311.].

AXL which is a chemosensitizer protein for breast cancer cells in response to epidermal growth factor receptor‐tyrosine kinase inhibitor and suppresses tumor growth. The clinical information show nuclear factor I (NFI)‐C and NFI‐X expression correlate with AXL expression in breast cancer patients. Following, we establish serial deletions of AXL pro...

The use of magnetic nanoparticles (MNPs) magnetized on applying an alternating magnetic field (AMF) to stimulate the thermal characteristics and to induce tumor apoptosis is a currently active area of research in cancer treatment. In previous work, we developed biocompatible and superparamagnetic polystyrene-sulfonic-acid-coated magnetic nanopartic...

Elevated Renal cell carcinoma (RCC) risk has been associated with the use of several antihypertensive medications but has not yet been elucidated in the populations prescribed alpha-1 blockers that are commonly used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS-BPH). The aim of...

Background/aim: Epithelial-mesenchymal transition (EMT) via Sonic Hedgehog (Shh) signaling may be one of the mechanisms of progression of castration-resistant prostate cancer (CRPC). In this study, we investigated the possible therapeutic effect of vismodegib, a new Shh inhibitor, in a mouse CRPC model. Materials and methods: We determined cell...

The development of novel magnetic nanoparticles (MNPs) with satisfactory biocompatibility for biomedical applications has been the subject of extensive exploration over the past two decades. In this work, we synthesized superparamagnetic iron oxide MNPs coated with polystyrene sulfonic acid (PSS-MNPs) and with a conventional co-precipitation method...

Background: Focal therapies for prostate cancer (PC) can reduce adverse events and do not lead to androgen-independent progression. Ultrasound could be used for cancer treatments if the repetition frequency is fitted to the purpose. We investigated the possible therapeutic effect of ultrasound irradiation on PC cells. Materials and methods: We i...

The effect of dyslipidemia on peritoneal dialysis (PD) patients based on the presence of residual renal function (RRF; renal creatinine clearance >2 mL/min/1.73 m 2) is unknown. Data from the Taiwan Renal Registry Data System between 2005 and 2012 were analyzed to estimate the association between dyslipidemia and mortality in PD patients. Long-term...

Studies on the aberrant control of extracellular matrices (ECMs) have mainly focused on the role of malignant cells but less on that of stromal fibroblasts during cancer development. Herein, by using paired normal and prostate cancer-associated stromal fibroblasts (CAFs) derived from a coculture cell model and clinical patient samples, we demonstra...

Introduction: To identify a specific biomarker for malignant prostate cancer progression and therapeutic target, we had demonstrated the correlation of ADAM9 expression and cancer progression. The aim is to clarify the association of ADAM9 and interactive proteins in malignant phenotypic progression. Methods: Knockdown of ADAM9 expression was condu...

Angiopoietin-like protein 1 (ANGPTL1) has been shown to act as a tumor suppressor by inhibiting angiogenesis, cancer invasion, and metastasis. However, little is known about the effects of ANGPTL1 on sorafenib resistance and cancer stem cell properties in hepatocellular carcinoma (HCC) and the mechanism underlying these effects. Here, we show that...

Previous studies of soluble factors in the tumor associated stromal cells demonstrated the elevation of CCL5 expression in prostate cancer patient sera that correlated wit malignant cancer progression. To evaluate the expression level of chemokine receptors in response to chemokines released by reactive stroma, quantitative PCR to evaluate the mRNA...

Distant organ metastasis of prostate cancer is a puzzle, and various theories have successively arisen to explain the mechanism of lethal cancer progression. While perhaps agreeable to many cancer biologists, the very statement of "seed and soil" proposed by Stephan Paget in 1881 is arguably still the major statement for organ-specific cancer metas...

Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer e...

Immunohistochemical analysis of osteonectin in prostate bone metastasis specimen. Tissue was stained with IgG control antibody (left), or anti-human osteonectin antibody (right); magnification, × 400. (PDF)

Background: Both benign prostatic hyperplasia (BPH) and Type-1 diabetes mellitus (T1DM) share similar epidemiologic features and are all associated with the insulin-like growth factor (IGF)-mediated hormonal imbalance. The purpose of this study is to understand whether exercise (EX) could alleviate DM and DM + BPH. Methods: Sprague-Dawley rats w...

Crosstalk between cancer and milieu cells plays a central role during cancer progression, which includes determine the faith of increasing metalloproteinase secretion by cancer epithelial cells. Here, we showed prostate tumor and stromal fibroblasts expressed opposite levels of Stromelysin-1 and -2 in both 3D co-culture and paired patient samples....

The L1 cell adhesion molecule (L1CAM) has been implicated in tumor progression of many types of cancers, but its role in prostate cancer and its application in targeted gene therapy have not been investigated. Herein, we demonstrated that the L1CAM was expressed in androgen-insensitive and highly metastatic human prostate cancer cell lines. The cor...

Tumor-stromal interaction is a dynamic process that promotes tumor growth and metastasis via cell-cell interaction and extracellular vesicles. Recent studies demonstrate that stromal fibroblast-derived molecular signatures can be used to predict disease progression and drug resistance. To identify the epigenetic role of stromal noncoding RNAs in tu...

The transmembrane cell adhesion protein ADAM9 has been implicated in cancer cell migration and lung cancer metastasis to the brain, but the underpinning mechanisms are unclear and clinical support has been lacking. Here we demonstrate that ADAM9 enhances the ability of tissue plasminogen activator (tPA) to cleave and stimulate the function of the p...

Bone marrow-derived mesenchymal stem cells (MSCs) are able to migrate to tumors, where they promote tumorigenesis and cancer metastasis. However, the molecular phenotype of the recruited MSCs at the tumor microenvironment and the genetic programs underlying their role in cancer progression remains largely unknown. By using a three-dimensional rotar...

Expression level of let-7 in the transfectants of 3A6 derivatives. The 3A6RWV normal MSCs (A) and the 3A6LNCaP and 3A6PC3 cancer-associated MSCs (B) were transfected with the indicated anti-miR and miRNA precursor for 72 hr, respectively, and then subjected to quantitative RT-PCR analysis for the expression of let-7c. Values are presented as the me...

List of primers and probes used in quantitative PCR. (PDF)

Quantification of adipogenesis and osteogenesis of 3A6 derivatives. (A) Oil red O staining to determine lipid droplet content after 21 days of differentiation and (B) Alizarin red S to detect calcium content 14 days after culture in osteogenic-induction media. The stained cells were quantified using a dye extraction method and data are represented...

PC3 cell proliferation under the coculture with 3A6 derivatives. Luciferase-expressing PC3 cells were seeded alone (control) or mixed with equal number of 3A6RWV or 3A6PC3 cells in 6-well plates. PC3 cell proliferation was determined by luciferase activity at indicated time points. Data were plotted as relative luciferase unit (RLU). (PDF)

Immunophenotype of MSC cell lines derived from 3-D RWV co-culture system at different passages. (PDF)

Comparison of cell proliferation among 3A6 derivatives by WST-1 assay performed daily for 5 days. The relative cell number was assessed by absorbance at 450 nm and presented as the fold change relative to the day of plating (day 0). Error bars indicate SD of triplicate measurements. NS = not significant. (PDF)

Reverse effects of IL-6 on exogenous let-7c-suppressed reactive phenotypes of MSCs. Cancer-associated 3A6PC3 cells transfected with let-7c precursor were induced to adipogenic differentiation or were cocultured with PC3 prostate cancer cells for transwell migration and invasion assay with the indicated concentration of recombinant IL-6. A microRNA...

Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM) 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene...

Scheme illustration of retroviral (up) and lentiviral (bottom) shRNA targets to ADAM9 mRNA and lentiviral shRNA targets to Reg4 mRNA. Targeted sequences were listed. (PDF)

Silencing ADAM9 enhanced radiotherapy efficacy. (a) Imaging of clonogenic analysis at 0, 10, 15, 20 and 25 Gy of radiation. PC3, PC3shGFP, PC3pLKO.1 and PC3shADAM9 cells were plated 100 cells/well and exposed to radiation the next day. Colony was measured 14-day after plating. (b) Statistic analyses of cologenic study of (a) that showed significant...

(a) Immunoblotting validated ADAM9 expression and revealed the knockdown of ADAM9 by Retroviral shADAM9-17130. Vector, pSM2C, were also transfected into PC3 and used as negative control. To select knockdown clone, several clones were also examined. Clone 7 was selected and used in most of our studies. (b) Immunoblotting confirmed knockdown effects...

Inhibition of PC3 prostate cancer cell growth in mice after knockdown ADAM9 expression. (a) Scheme illustration of subcutaneous inoculation of PC3pSM2C and PC3shADAM9 in same mice. PC3pSM2C was implanted in the left size and PC3shADAM9 in the right site of lower back of same mice. (b) Bioluminescence imaging obtained at day-30 post inoculation. Onl...

Histopathology of tumors after therapies revealed reduction of ADAM9 and Ki-67 staining in shADAM9 group. H & E staining of tumor region treated either with PBS, shGFP lentivirus or shADAM9 lentivirus therapies (a-c). ADAM9 immunohistochemistry staining showed positive of ADAM9 in PBS and shGFP therapies (d and e). (f) By contrast, decreased ADAM9...

Intersection microarray analyses revealed the increased expression of CD33 and decreased of REG4 expression after knockdown of ADAM9 expression. (a) Two microarrays and intersection analysis of common gene changes between retrovirus and lentivirus shADAM9 profiling. Results indicate that mRNA levels of CD33 increased and those of REG4, IGFBP3, and...

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Recent evidence has demonstrated that detection of changes in the levels of urinary vascular endothelial growth factor (VEGF) and tissue a disintegrin and metalloproteinase 9 (ADAM9) is effective in determining prostate cancer progression. To evaluate the combined application of VEGF and ADAM9 as early progression markers of lethal phenotypic cance...

The etiology of epilepsy is a very complicated, multifactorial process that is not completely understood. Therefore, the availability of epilepsy animal models induced by different mechanisms is crucial in advancing our knowledge and developing new therapeutic regimens for this disorder. Considering the advantages of zebrafish, we have developed a...

Cell-based carriers were recently exploited as a tumor-targeting tool to improve systemic delivery of oncolytic viruses for cancer therapy. However, the slow clearance of carrier cells from normal organs indicates the need for a controllable system which allows viral delivery only when the carrier cells reach the tumor site. In this communication,...

Environmental factors have profoundly influence on cancer cell directional migration and metastasis. Previously, we have showed the increasing of CCL5 in tumor associated stromal cells and in patient sera with cancer progression. To verify the role of CCL5 in organ specific cancer metastasis, cellular and molecular studies of cancer migratory activ...

Cell-based carriers were recently exploited as a tumor-targeting tool to improve systemic delivery of oncolytic viruses for cancer therapy. However, the slow clearance of carrier cells from normal organs indicates the need for a controllable system which allows viral delivery only when the carrier cells reach the tumor site. In this study, we sough...

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL A disintegrin and metalloproteinase (ADAM) superfamily, has been demonstrated involved in tumor progression and metastasis. Previously, Fritzsche et al., performed the clinic evaluation of ADAM9 expression and indicated the correlation between ADAM9 expression and poor progno...

Alteration of integrin composition is highly correlated with cancer malignancy and metastasis. Recent evidence demonstrated the metastasis activities involved the interaction of integrin and ADAM gene family, such as ADAM8, ADAM9, ADAM10 and ADAM17. These may either stabilized or cleavage of integrin-matrice interaction at the lamellipodia of cance...

Recent studies demonstrated the importance of ADAM9 in prostate cancer relapse upon therapy. In this study, we determined the role of ADAM9 in the therapeutic resistance to radiation and chemotherapy. ADAM9 was either transiently or stably knocked down in C4-2 prostate cancer cells. The sensitivity of ADAM9 knockdown cells toward radiation and chem...

Advanced renal cell carcinoma (RCC) frequently develops skeletal metastasis and is highly resistant to conventional therapies. We hypothesized that the osteocalcin (OC) promoter may be a promising gene delivery system for RCC targeted gene therapy because osteotropic tumors gain osteomimetic properties and thrive in the new environment by exhibitin...

The L1 cell adhesion molecule (L1CAM) has been implicated in tumor progression of many types of cancers, but its role in oral squamous cell carcinoma (OSCC) has not been investigated. In the present study, we demonstrated overexpression of L1CAM in OSCC cells, but not in normal keratinocytes, using both clinical specimens and cell lines. This overe...

HS-27a human bone stromal cells, in 2D or 3D coultures, induced cellular plasticity in human prostate cancer ARCaP(E) and ARCaP(M) cells in an EMT model. Cocultured ARCaP(E) or ARCaP(M) cells with HS-27a, developed increased colony forming capacity and growth advantage, with ARCaP(E) exhibiting the most significant increases in presence of bone or...

Human bone stromal cells, after three-dimensional coculture with human prostate cancer (PCa) cells in vitro, underwent permanent cytogenetic and gene expression changes with reactive oxygen species serving as mediators. The evolved stromal cells are highly inductive of human PCa growth in mice, and expressed increased levels of extracellular matrix...

MicroRNAs (miRNA) are gene regulators and play an important role in response to cellular stress. Using multiplexed quantitative real-time PCR we performed global miRNA screening of prostate cancer cells in response to radiation treatment. Several miRNA were significantly altered in response to radiation treatment. Significant changes were observed...

The A Disintegrin And Metalloprotease (ADAM) family is a group of transmembrane proteins containing cell adhesive and proteolytic functional domains. ADAM9 expression was shown to be mediated by androgen receptor (AR) and stress conditions. This study determined a common mediator responsible for ADAM9 protein regulation which supports human prostat...

The homeostatic status of cellular tissue results from a dynamic balance of cell proliferation, differentiation, and apoptosis. These unique organ-specific phenotypes are conferred and maintained by interaction between epithelium and adjacent stroma through intimate intercellular signaling pathways. Similarly, the tumor microenvironment, or stroma,...

Cancer is not a single cell disease and its existence and behavior are constantly modulated by the host. Cancer gene expression and genetics are also highly dynamic and are regulated epigenetically by the host. In this chapter, we describe the molecular pathways leading to an unusual property of cancer cells: the ability to mimic the host microenvi...

The ADAM (a disintegrin and metalloprotease) family is a group of transmembrane proteins containing cell adhesive and proteolytic functional domains. Microarray analysis detected elevated ADAM9 during the transition of human LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent and metastatic state. Using a prostate tiss...

Cancer is not a single-cell disease, and its existence and behavior are constantly modulated by the host. Cancer gene expression and genetics are also highly dynamic and are regulated epigenetically by the host through gene-environment interaction. In this article, we describe the molecular pathways leading to an unusual property of cancer cells: t...