Eugene Liu

Wan Fang Hospital · Department of Medicine

Cancer immunotherapies, such as checkpoint blockade of programmed cell death protein-1 (PD-1), represents a breakthrough in cancer treatment, resulting in unprecedented results in terms of overall and progression-free survival. Discovery and development of novel anti PD-1 inhibitors remains a field of intense investigation, where novel monoclonal a...

Background: Cetuximab, the first approved EGFR targeting therapeutic antibody, is currently used to treat colorectal cancer and head and neck cancer. While effective, cetuximab is associated with a higher rate of skin rash, infusion reactions, and gastrointestinal toxicity, which was suggested to be linked to the presence of heterogenous glycan co...

Rituximab in combination with chemotherapy has shown efficacy in patients with diffuse large B-cell lymphoma (DLBCL) for more than 15 years. HLX01 was developed as the rituximab biosimilar following a stepwise approach to demonstrate biosimilarity in analytical, pre-clinical, and clinical investigations to reference rituximab. With demonstrated pha...

Objective To compare the efficacy of low-dose or no aspirin with conventional high-dose aspirin for the initial treatment in the acute-phase of Kawasaki disease (KD). Design A meta-analysis and systematic review of randomised control trials and cohort studies. Methods All available articles that compared different dosage of aspirin in the acute-p...

Background In February 2019, the National Medicinal Products Administration (NMPA) approved the first China-manufactured rituximab (RTX) biosimilar, HLX01, for the treatment of non-Hodgkin's lymphoma in accordance to the development of biosimilar guidelines with stepwise approach demonstrating bioequivalence. HLX01 was also developed as a novel dru...

Background HLX07 is a fully-humanised anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) with re-engineered Fab rendering its less immunogenic and better binding affinity than cetuximab. In-vivo studies of HLX07 demonstrated either equal or superior efficacy to cetuximab at the same dose level. Here, we present the data from the...

Background HLX10, a fully humanized IgG4 monoclonal antibody against the programmed death-1 (PD-1) receptor blocking PD-1, increased functional activities of human T-cells and showed in-vitro antitumour activity in xenograft models. The combined inhibition of PD-1 and VEGFR pathways may enhance a sustained suppression of cancer-related angiogenesis...

Background HLX02, a fully-humanised anti-HER2 monoclonal antibody, was developed as trastuzumab (TZB) biosimilar to potentially increase treatment accessibility. The clinical program was developed in consultation with China National Medical Products Administration (NMPA) and European Medicines Agency (EMA) for global development. Previously, we rep...

Background HLX01, the first China (CN)-manufactured rituximab (RTX) biosimilar, was approved by the National Medicinal Products Administration (NMPA) for the treatment of non-Hodgkin's lymphoma on 22-February-2019, and was concurrently developed as a novel drug for rheumatoid arthritis (RA) since the indication has not been approved in CN. Here, we...

Background HLX01, the first-ever China (CN)-manufactured rituximab (RTX) biosimilar, was approved by National Medicinal Products Administration (NMPA) for the treatment of diffuse large B-cell lymphoma (DLBCL) on 22 February 2019, and was concurrently developed as a novel drug to treat rheumatoid arthritis (RA) in CN since the indication has not be...

Background The introduction of trastuzumab in combination with chemotherapy has significantly improved clinical outcomes for patients with HER2-positive breast cancer. HLX02 was developed as a trastuzumab biosimilar with the potential to increase market competition and treatment accessibility in China and around the world. Methods We conducted a r...

Background Biologic products, such as rituximab and adalimumab, have revolutionized the treatment for chronic inflammatory disorders, providing an option to patients who were non-responsive to conventional systemic therapies. In China, rituximab is only approved for the treatment of certain haematologic malignancies. At present, there are several a...

Background Adalimumab first launched in China in August 2010 with now more than 10 million people have its indications.1, 2 However, the relative high cost of the biologic drug limits the treatment accessibility and reduces the quality of life in patients living with the chronic inflammatory disease like rheumatoid arthritis and psoriasis. In accor...

Background The nuclear translocation of epidermal growth factor receptor (EGFR) has been considered to play a role in carcinogenesis. However, the relevance of differentially located EGFR proteins in lung cancer remains unclear. Methods We examined 161 patients with primary lung adenocarcinoma to detect EGFR expression in lung cancer cells using im...

e14078 Background: EGFR is a validated target for anti-cancer drug development. Several anti-EGFR monoclonal antibodies (mAb) are used in clinics, but associated with a variety of toxicities. A new anti-EGFR mAb might offer better efficacy with less toxicities. Methods: we have developed a new humanized anti-EGFR mAb, HLX07, through engineering of...

[This corrects the article DOI: 10.1371/journal.pone.0156260.].

Chronic myeloid leukemia (CML) is a myeloproliferative disease. Imatinib (IM), the first line treatment for CML, is excessively expensive and induces various side effects in CML patients. Therefore, it is essential to investigate a new strategy for improving CML therapy. Our immunoblot data revealed that RanGTPase activating protein 1 (RanGAP1) pro...

RanGAP1 protein was expressed in CML cells. The RanGAP1 protein levels were measured using an immunoblot assay in granulocytes and monocytes from CML patient, and K562 cells. GAPDH was used as an internal control. The CRKL phosphorylation level on Tyr-207 is activated by BCR-ABL, which is used as a marker of CML cells. (TIFF)

Combination of RanGAP1 knockdown by miR-1301 and IM treatment significantly induced BCR-ABL nuclear entrapment in miR-1301-transfected K562 cells. K562 cells were transfected with pCDH (vector only) or the miR-1301 plasmid and subsequently treated with 250 nM IM for 48 h. The protein levels were observed using immunofluorescence staining through de...

RanGAP1 expression-associated miRNA level was decreased in K562 cells compared with that in normal monocytes and granulocytes. (A) The list of twenty-four miRNAs significantly downregulated in K562 cells respectively compared to normal monocytes and granulocytes from healthy volunteers (FC ≦ 0.5; p value ≦ 0.05) according to the microarray data fro...

IM decreased K562 cells viability in a dose dependent manner. The viability of K562 cells was measured by an MTT assay after treatment with the indicated doses of IM for 48 h. The results are presented as means + SD of three independent experiments. Data abcdef without the same letter are significantly different from each group (p < 0.05). (TIFF)

Basic clinical parameters of the CML patients involved in the study. (TIFF)

Basic clinical parameters of the healthy volunteers involved in the study. (TIFF)

Acute myeloid leukemia (AML) is a hematological malignant disorder. AML cells are not susceptible to chemotherapeutic drugs because of their multidrug resistance (MDR). Antitubulin agents are currently employed in cancer treatments; however, drug resistance results in treatment failures because of MDR1 expressing cancer cells. We previously synthes...

Numerous FLT3 inhibitors have been explored as a viable therapy for the treatment of acute myeloid leukemia (AML). However, clinical data have been underwhelming due to incomplete inhibition of FLT3 or the emergence of resistant mutations treated with these older agents. We previously developed a series of 3-phenyl-1H-5-pyrazolylamine derivatives a...

The FMS-related tyrosine kinase 3 (FLT-3) gene is a hematopoietic growth factor receptor gene, an independent negative prognostic factor, which affects the proliferation and differentiation of stem cells or hematopoietic progenitor cells. Patients with FLT-3 gene mutations have a worse prognosis and responsiveness to chemotherapy than those without...

The polymerization of tubulin molecules forms microtubules which are considered an attractive target for cancer treatment. Herein, we synthesized a new tubulin inhibitor, MPT0B169 (2-dimethylamino-N-[1-(4-methoxy-benzenesulfonyl)-2, 3-dihydro-1H-indol-7-yl]-acetamide) and demonstrated its action in leukemia cell lines HL60 and NB4 and lymphoma cell...

Abstract Areca quid (AQ) chewing is a popular oral habit, especially in Southeast Asia cultures, in which children may be engaged in the addictive habit early in their lives. Extracts of areca nuts, the main component of AQ, have been shown to affect the functionality of T-cells. However, the potential influence of ANE on the development of T-cells...

Background: The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population. Methods: In this phase 3 tr...

Due to the development of drug resistance, the outcome for the majority of patients with acute myeloid leukemia (acute myelogenous leukemia; AML) remains poor. To prevent drug resistance and increase the therapeutic efficacy of treating AML, the development of new combinatory drug therapies is necessary. Sonic hedgehog (Shh) is expressed in AML bio...

First-line drug treatment for tuberculosis (TB) is frequently associated with liver toxicity. The goal of this study was to examine the association between UDP-glucuronosyl-transferase 1A1 (UGT1A1) genetic variations and anti-tuberculosis drug-induced hepatotoxicity (ATDH). A total of 98 patients, including 17 patients with ATDH, were enrolled; com...

APS (Acta Pharmacologica Sinica), the top pharmacology research journal based in China, publishes original articles and reviews on all aspects of pharmacology and the related life sciences

This study was aimed to evaluate the correlation between the polymorphisms of the UDP-glucuronosyltransferases1A7 (UGT1A7) gene and the risk of lung carcinogenesis in the Taiwanese population. A total of 230 lung cancer patients and 230 age- and gender-matched healthy individuals were enrolled in this case control study. UGT1A7*1 was defined as a h...

Reactive thrombocytosis (RT) in pediatric patients is common, but usually without symptoms. The incidence of RT is different depending on age. Mostly, we reason that RT is a phenomenon, nevertheless the diagnostic value of RT is little known. Therefore, the aim of this study was to determine the association of RT and clinical or laboratory characte...

BACKGROUND: Non small cell lung cancer EGFR mutations are prevalent in the East Asian population, especially in female non-smokers, the L858R and del 747-753 in exons 18-21 of the EGFR tyrosine kinase domains are activating mutations with increased sensitivity to the EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. EGFR gene amplific...

Since lung cancer is often diagnosed at advanced stages, patients usually require systemic therapy, such as chemotherapy or targeted agents, to control their disease. In the past, patients are treated in a trial-and-error fashion. Now with the advances in genomic sequencing, the application of mutation screening particularly in epidermal growth fac...

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Acute myeloid leukemia (AML) is a highly malignant hematopoietic tumor characterized by an abnormal proliferation of myeloid progenitor cells, decreased rate of self-destruction and an arrest in cell differentiation. The internal tandem duplication mutations of FMS-like...

The FMS-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase with important roles in hematopoietic stem/progenitor cell survival and proliferation. FLT3 is over-expressed in the majority of acute myeloid leukemia (AML) and the presence of FLT3 active mutations is associated with poor prognosis, implicating FLT3 as a potential target for AML...

We conducted a multi-center, randomized and laboratory-blinded clinical trial with subgroup analyses, involving adults aged greater than 60 years old (range 61-86 years old), to investigate the immunogenicity and the potential factors affecting the immune response of a monovalent, unadjuvanted, inactivated, split-virus vaccine. A total of 107 subje...

Deep vein thrombosis is a common disease entity to which attention should be paid due to its complication of pulmonary embolism. This disease usually has precipitating factors such as obesity, varicose veins or non- ambulation. Congenital coagulation defects should be suspected if patient has recurrent deep vein thrombosis without identifiable prec...

c-Myc oncogene is critical for the development of hepatocellular carcinoma. Given the successful use of small-molecule inhibitors on cancers, targeting c-Myc with small-molecule inhibitors represents a promising approach. The potential of using small-molecule c-Myc inhibitor, 10058-F4, was evaluated on hepatocellular carcinoma cell lines, HepG2 and...