Chueh-Chuan Yen

Taipei Veterans General Hospital · Hematology Division

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus gu...

Background: Liposarcoma (LPS) is one of the most common soft tissue sarcoma (STS) subtypes. Both well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) have 12q13-15 amplification. Mouse double minute 2 homolog (MDM2) is one of the most important oncogenes within this region. Ferroptosis is a unique type of necrotic cell death featured ac...

Background The prognosis of adrenocortical carcinoma (ACC) is poor but highly variable. The present study aimed to characterize patients with ACC at a single center in Taiwan and to determine the prognostic predictors of overall and progression-free survival.Methods Medical records of patients, who were diagnosed with ACC at Taipei Veterans General...

[This corrects the article DOI: 10.3389/fonc.2022.883399.].

Purpose: Satisfactory treatment options for advanced leiomyosarcoma (LMS) and liposarcoma (LPS) are limited. The LEADER study (NCT03526679) investigated the safety and efficacy of lenvatinib plus eribulin. Patients and methods: LEADER is a multicenter phase Ib/II study for advanced LMS or LPS. The phase Ib part enrolled six patients to determine...

11506 Background: There are limited treatment options for advanced LPS and LMS, the two most common histologies in soft tissue sarcoma. Patients (pts) treated with E had an improved overall survival (OS) compared to dacarbazine but with an unsatisfactory 4% objective response rate (ORR). Early studies of L, a multi-targeted anti-angiogenic inhibito...

Background Ripretinib was recently approved for the fourth-line targeted therapy for advanced gastrointestinal stromal tumor (GIST) refractory to imatinib, sunitinib, and regorafenib based on the pivotal INVICTUS phase III study. The INVICTUS study demonstrated significantly improved median progression-free survival (PFS) of 6.3 months and an overa...

Purpose: Limited long-term data are available on immune checkpoint inhibitor use in patients with advanced esophageal squamous cell carcinoma (ESCC). We report three-year follow-up data from our study of nivolumab versus chemotherapy (paclitaxel or docetaxel) in patients with previously treated ESCC. Experimental design: ATTRACTION-3 was a rando...

Background Multidisciplinary management strategies are standard in esophageal cancer. Based on a multidisciplinary tumor board (MTB) database in a high-volume center, we aimed to evaluate real-world treatment patterns and patient outcomes in patients with esophageal cancer. In addition, we determined the impact of MTB discussions on patient prognos...

204 Background: Previous results from the ATTRACTION-3 phase 3 trial demonstrated a significant improvement in overall survival and a favorable safety profile compared with taxane chemotherapy (CT) in previously-treated ESCC patients. To our knowledge, no long-term efficacy and safety data of this immune checkpoint inhibitor has been reported in ES...

11517 Background: Oraxol is a combination of oral paclitaxel and a novel oral P-glycoprotein inhibitor, HM30181A. Cutaneous angiosarcomas are highly aggressive malignant tumors with poor prognosis. Currently there is no FDA-approved treatment. Methods: This is an open label study evaluating the activity, safety and tolerability of Oraxol 205mg/m ²...

11507 Background: For advanced LPS and LMS, the two most common histologies in soft tissue sarcoma, there are limited treatment options that readily balance efficacy and toxicity. Patients (pts) treated with E had an improved median overall survival (OS) in a phase III randomized study compared to dacarbazine but with an unsatisfactory 4% objective...

Importance Patients with advanced soft tissue sarcoma (STS) have a median overall survival of less than 2 years. In a phase 2 study, an overall survival benefit in this population was observed with the addition of olaratumab to doxorubicin over doxorubicin alone. Objective To determine the efficacy of doxorubicin plus olaratumab in patients with a...

Background: Parosteal osteosarcoma is a unique low grade osteosarcoma. Two separate oncogenes, MDM2 and CDK4, are specifically amplified in parosteal osteosarcoma. Its clinical behavior is usually indolent. In some occasions, it may progress to high grade and become fatal. Malignant transformation with high grade differentiation is the most reliab...

Liposarcoma (LPS) is one of the most frequently reported type of soft‑tissue sarcoma (STS). Well‑differentiated (WD) LPS and dedifferentiated (DD) LPS are the two most common subtypes. Chemotherapy has been considered to be ineffective in LPS, and novel treatment agents are thus necessary. In this study, we reanalyzed two published microarray data...

Gastrointestinal stromal tumors (GISTs) are gastrointestinal tract sarcomas that commonly contain a mutation in the tyrosine kinases, KIT and platelet‑derived growth factor receptor A (PDGFRA). Imatinib, sunitinib and regorafenib are all effective tyrosine kinase inhibitors; however, acquired resistance is inevitable. The E26 variant 1 (ETV1) pathw...

Background: Asian studies on soft tissue sarcoma (STS) incidence, irrespective of the primary site, are scant. Methods: STS data were acquired from the population-based 2007-2013 Taiwan Cancer Registry of the Health and Welfare Data Science Center, Taiwan. Histological subtype-, site-, sex-, and age-specific STS incidence rates were analyzed acc...

e22524 Background: Eri, although approved for advanced LPS, has limited activity in terms of tumor shrinkage. Anti-angiogenic agents have shown to increase tumor response in certain cancer types. This study aims to understand the safety, optimal dose, and efficacy of the combination of lenv, a multi-kinase anti-angiogenic inhibitor, and eri in LMS...

Population-based studies on soft tissue sarcomas (STS) incidence beyond extremities and trunk wall are lacking in Asia. In this study, we aimed to report the incidences of STS arise in any part of the body. The data of primary STS registered in the population-based Taiwan Cancer Registry during 2007 and 2013 was acquired via the Health and Welfare...

In previous studies by the authors, aurora kinase A (AURKA) was demonstrated as an independent poor prognostic marker for the recurrence of localized gastrointestinal stromal tumors (GISTs) and for the progression of advanced GISTs. In the present study, the prognostic effect of genes involved in cell cycle regulation in GISTs was further examined....

e15119 Background: There are increasing numbers of elderly patients with colorectal cancer (CRC). With the advance of cancer treatment in recent years, more elderly CRC patients receive curative surgery and multidisciplinary cancer treatment. The purpose of this study is to identify the risk factors of mortality and to improve survival of these pat...

Background: Gastrointestinal stromal tumors (GISTs) are caused by the constitutive activation of KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations. Imatinib selectively inhibits KIT and PDGFR, leading to disease control for 80%-90% of patients with metastatic GIST. Imatinib resistance can occur within a median of 2-3 years du...

PurposeAdjuvant FOLFOX (5-fluorouracil and oxaliplatin) chemotherapy benefits stage III colon cancer patients. However, it still results in side effects and increased cost. Reducing cycles had been thought to decrease these problems. This retrospective study aimed to find the appropriate number of treatment cycles that are sufficient for treating t...

Gastrointestinal stromal tumors (GIST) is gastrointestinal tract sarcoma which commonly contains a mutation in the KIT or PDGFRA. Imatinib mesylate, a specific tyrosine kinase inhibitor of the KIT and PDGFRA, causes regression or stabilization of disease in most of the patients with metastatic GIST. However, acquired resistance to imatinib is inevi...

Background: Enumerating hematopoietic progenitor cells (HPCs) by using an automated hematology analyzer is a rapid, inexpensive, and simple method for predicting a successful harvest compared with enumerating circulating CD34+ cells. However, the optimal HPC cutoff count and the indicating factors to be considered for improved predicting have not...

To identify the prognostic factors and long-term outcome of the Ewing sarcoma family of tumors (ESFT), data on 50 patients with ESFT treated at Taipei Veterans General Hospital between February 1991 and March 2014 were retrospectively considered. The influence of patient demographics, tumor features, and clinical and therapeutic parameters on overa...

The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade o...

134 Background: Our preclinical studies showed that AUY922 treatment could induce downregulation of KIT protein and apoptosis in both imatinib-sensitive and -resistant GIST cells (Autophagy 2013). This prospective, phase II trial evaluated the efficacy and safety of AUY922 in patients with metastatic GISTs after failure or intolerance to imatinib a...

Polo-like kinase 1 (PLK1), a serine/threonine kinase and an oncogene, is crucial in regulating cell cycle progression. PLK1 also has been demonstrated as a potential target of osteosarcoma (OS) by using short hairpin RNA libraries in lentiviral vectors for screening of protein kinase. In preclinical studies, GSK461364, a potent and selective ATP-co...

Background: Surgery is the potentially curative treatment for retroperitoneal sarcoma (RS), but complete resectability is frequently a challenge. This study aimed to characterize the clinical features, prognostic factors and treatment outcomes. Methods: A cohort of 144 patients with RS was surveyed retrospectively from January 1st, 2000 to July...

Most epidemiological studies of soft tissue sarcoma (STS) were performed in the Western countries, and only limited data highlighting that in the Asian population. The aim of this study is to conduct a comprehensive analysis for the incidence rates of STS in Taiwan. This was a population-based study analyzing the incidence rates and trends of the p...

The purpose of this study is to determine the features of second primary malignancies (SPMs) among patients with prior colorectal cancer (CRC) using a nationwide population-based dataset. Patients with CRC newly diagnosed between 1996 and 2011, and >1 year of follow-up were recruited from the Taiwan National Health Insurance database. Standardized...

Cholangiocarcinoma (CCA) is characterized by a uniquely aggressive behavior and lack of effective targeted therapies. After analyzing the gene expression profiles of seven paired intrahepatic CCA microarrays, a novel sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P) pathway and a novel target gene, SPHK1, were identified. We hypothesized t...

The impact of KRAS signaling on cancerous inhibitor of protein phosphatase 2A (CIP2A) expression has not yet been explored. We investigated the impact of KRAS on CIP2A expression in colorectal cancer patients after colorectal liver metastasectomy. We examined CIP2A expression by immunohistochemistry (IHC) and used direct sequencing to identify the...

Our previous study demonstrated NVP-AUY922, a HSP90AA1 inhibitor, could enhance mutant KIT degradation in gastrointestinal stroma tumor (GIST) cells through both proteasome- and autophagy-mediated pathways. Herein, we showed rapamycin, a MTOR inhibitor and autophagy inducer, could reduce total and phospho-KIT expression levels and enhance apoptosis...

Purpose: To identify the prognostic factors and evaluate the impact of chemotherapy regimens on the outcomes of pediatric osteosarcoma of the extremities. Methods: Patients younger than 18 years and diagnosed with high-grade osteosarcoma of the extremities during the period between January 2004 and December 2011 were included for retrospective a...

Aberration in DNA replication is a major cause to genome instability that is a hallmark of cancer cells. Cell division cycle 6 (Cdc6) and c-Myc have a critical role in the initiation of DNA replication. However, whether their interaction induces epithelial-mesenchymal transition (EMT) and promotes tumorigenesis in in vivo animal model remains uncle...

Purpose: We aimed to compare the treatment efficacy of cetuximab versus bevacizumab in combination with either irinotecan-based or oxaliplatin-based regimens (targeted triplet) as the first-line treatment for patients with metastatic colorectal cancer. Methods: Between April 2005 and March 2012, patients (n = 158) diagnosed with metastatic color...

Ifosfamide is an alkylating antineoplastic prodrug used to treat many solid tumors. The metabolism of ifosfamide is via CYP450 3A4 and 2B6 and produces active ifosfamide mustard, the toxic metabolite acrolein and chloroacetaldehyde (CAA). Additionally, CAA is believed to induce proximal tubular dysfunction which results in Fanconi's syndrome. It is...

Purpose: Although imatinib mesylate (IM) has revolutionized the management of gastrointestinal stromal tumors (GISTs), drug resistance remains a challenge. Previous studies have shown that the expression of aurora kinase A (AURKA) predicts recurrence in patients with primary surgically-resected GISTs. The current study aims to evaluate the signific...

Primary bone cancer (BC) incidence by age has not been surveyed in Asia. The incidence patterns of nine subtypes of primary BCs registered between 2003 and 2010 were analyzed from Taiwan cancer registry data. More specific analyses were conducted within age groups (Group I: 0-24 years; Group II: 25-59 years; and Group III: 60-85+ years). A total of...

A dozen clinical trials examining a combination of temsirolimus and cetuximab in treating metastatic colon cancer are currently underway. We investigated the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in the synergism between temsirolimus and cetuximab in colon cancer. Five colon cancer cell lines were used for in vitro studies....

Polo-like kinase 1 (PLK1), a critical cell cycle regulator, has been identified as a potential target in osteosarcoma (OS). 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2), a prostaglandin derivative, has shown its anti-tumor activity by inducing apoptosis through reactive oxygen species (ROS)-mediated inactivation of v-akt, a murine thymoma viral onc...

Objective: Primary bone lymphoma is a rare disorder, accounting for less than 1% of all cases of malignant lymphoma. Primary bony diffuse large B-cell lymphoma (PBDLBCL) is the most common histological type. In our study, a favorable response and lower risk of emergent surgery were observed following the administration of systemic chemotherapy wit...

CRNN gene expression is downregulated in esophageal squamous cell carcinoma (ESCC), although its clinical implications in esophageal cancer remain unclear. We performed integrated microarray analysis and identified the CRNN gene as 1 of the major downregulated genes in ESCC. CRNN downregulation was validated at the nucleic acid level in 16 ESCC cas...

The molecular and genetic changes underlying esophageal squamous cell carcinoma (ESCC) tumor formation and rapid progression are poorly understood. Using high-throughput data analysis, we examined molecular changes involved in ESCC pathogenesis and investigated their clinical relevance. Five independent microarray datasets were examined for differe...

Advanced gastrointestinal stromal tumors (GIST), a KIT oncogene-driven tumor, on imatinib mesylate (IM) treatment may develop secondary KIT mutations to confer IM-resistant phenotype. Second-line sunitinib malate (SU) therapy is largely ineffective for IM-resistant GISTs with secondary exon 17 (activation-loop domain) mutations. We established an i...

The comparisons of inhibitory effects of imatinib on KIT single mutants using western blotting analysis and Luminex assay. (a) COS-1 cells transfected with KIT single mutants were starved and treated with indicated doses of IM for 30 minutes. The total expression and degree of phosphorylation of KIT were determined by western blot analysis or Lumin...

Stereo views of SU and sorafenib binding to KIT showing key hydrogen bonds formed with A599 and R684 in different models. (TIF)

Primers used for mutagenesis of KIT. (a) Primers used for site directed mutagenesis of KIT exon 9Ala502_Tyr503insAlaTyr, 11Val560Asp, 11Val555_Leu576del, 13Val654Ala, 14Thr670Ile, and 17Asp820Gly, and 17Asn822Lys mutants. (b) Primers used for slicing overlap extension of KIT exon 11Val555_Leu576del mutants. (DOC)

4099 Background: We investigated the efficacy and safety of adding cetuximab to twice-weekly paclitaxel/cisplatin-based concurrent chemoradiotherapy (CCRT), followed by surgery, for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients with locally advanced ESCC (T3N0-1M0 or T1-3N1M0 or M1a by AJCC 2002) were t...

Gastrointestinal stromal tumor (GIST) is a prototype of mutant KIT oncogene-driven tumor. Prolonged tyrosine kinase inhibitor (TKI) treatment may result in a resistant phenotype through acquired secondary KIT mutation. Heat shock protein 90 (HSP90AA1) is a chaperone protein responsible for protein maturation and stability, and KIT is a known client...

Rationale: Cancer stem cell (CSC) theory has drawn much attention, with evidence supporting the contribution of stem cells to tumor initiation, relapse, and therapy resistance. Objectives: To screen drugs that target CSCs to improve the current treatment outcome and overcome drug resistance in patients with lung cancer. Methods: We used public...

We explored the impact of frequency of surveillance imaging on disease-specific survival (DSS) in patients with extremity soft tissue sarcoma (STS). Locoregional imaging (LRI) and chest imaging (CI) were used to detect local recurrence (LR) and distant metastasis (DM), respectively. Relapsing patients were retrospectively assigned to more frequent...

In metastatic colorectal cancer, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is a predictive biomarker for anti-epidermal growth factor receptor (EGFR) treatment and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a prognostic biomarker. We aimed to determine the impact of KRAS and BRAF mutation as determined from liver met...

To investigate the impact of concurrent chemoradiotherapy (CCRT) on stage IV rectum cancer. Between 2000 and 2011, 297 consecutive patients diagnosed with stage IV rectum cancer (synchronous metastasis) were enrolled. Cox proportional hazard analyses were used for prognostic factors determination, and the Kaplan-Meier method was used for survival a...

Objective: The mammalian target of rapamycin signaling pathway has been implicated in therapeutic resistance in several types of cancer. However, the significance of mammalian target of rapamycin activation in chemoradiotherapy sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma treated with chemoradiotherapy remain u...

Carcinoma of unknown origin has a poor outcome and usually occurs in elderly patients. In this article, we analyzed the prognostic factors in elderly patients with cancer of unknown primary site (CUP) for treatment considerations. Patients >70 years old with histologically proven carcinoma were retrospectively reviewed. The prognostic factors were...

Background: Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower verteb...

Validation of the transmission, expression and function of testing lines in stable transgenics using genotyping, RT-PCR and Western blot analysis. Assay of the stable transmission and expression of transgenes in different testing lines at the DNA and mRNA levels by genotyping (A) and RT-PCR (B), respectively. The relative position of the primers us...

Network of the deregulated genes in obsese transformed zebrafish. Red and green text donate genes with increased and decreased expression, respectively, in Tg(krt4:Hsa.myrAkt1)cy18 when the wild-types are compared. The microarray data of triplicated assay were submitted to NCBI Gene Expression Omnibus under accession numbers GSM542371 to GSM542373....

The PCR amplicon size and primer sequences used to perform real-time RT-PCR. (XLS)

Measurement of mRNA expression level of two genes located adjacent to the chromosomal insertion site in multiple tissues by real-time RT-PCR. (XLS)

For completely resected primary gastrointestinal stromal tumors (GISTs), mitotic rate, tumor size, and tumor location are important risk factors for recurrence. However, molecular markers for recurrence are still lacking. We reanalyzed GIST gene expression profile GSE8167 available from the Gene Expression Omnibus (GEO) and confirmed the prognostic...

Minimally invasive interventional biopsy procedures have the advantages of accurate localization, small incisions, and rapid recovery. The purpose of this study was to clinically test and evaluate the efficacy of the magnetic resonance imaging (MRI)-guidance techniques for obtaining musculoskeletal biopsies using the appropriate imaging modalities...

High-dose tissue-specific delivery of therapeutic agents would be a valuable clinical strategy. We have previously shown that repeated transcranial focused ultrasound is able to increase the delivery of Evans blue significantly into brain tissue. The present study shows that repeated pulsed high-intensity focused ultrasound (HIFU) can be used to de...

The cancerous inhibitor of protein phosphatase 2A (CIP2A) oncoprotein is overexpressed in colon cancer tissue compared to normal colon mucosa. We investigated the impact of CIP2A on colon cancer. A tissue microarray consisting of 167 colon cancer specimens was investigated. The association between CIP2A and clinicopathological parameters was analyz...