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Dramatic advances in immune therapy have emerged as a promising strategy in cancer therapeutics. In addition to chemotherapy and radiotherapy, inhibitors targeting immune-checkpoint molecules such as cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death receptor-1 (PD-1) and its ligand (PD-L1) demonstrate impressive clinical benefits in clinical trials. In this review, we present background information about therapies involving PD-1/PD-L1 blockade and provide an overview of current clinical trials. Furthermore, we present recent advances involving predictive biomarkers associated with positive therapeutic outcomes in cancer immunotherapy.

Trial Information ClinicalTrials.gov Identifier: NCT00076609 Sponsor: Yiviva Inc. Principal Investigator: Yun Yen IRB Approved: Yes Lessons Learned A PHY906 and capecitabine combination could be effective as a salvage therapy for patients with hepatocellular carcinoma (HCC) previously treated with multiple systemic therapies. This traditional Chinese medicine formulation can work with Western cancer chemotherapeutic agents to improve clinical outcomes or alleviate side effects for patients with advanced HCC. Background This study aimed to evaluate efficacy and safety of capecitabine combined with a PHY906 (a pharmaceutical-grade formulation of four traditional Chinese herbs) in the treatment of advanced hepatocellular carcinoma (HCC) in Asian patients who were positive for hepatitis B virus (HBV). Methods This study was an open-label, phase II safety and efficacy clinical trial of PHY906 and capecitabine in patients with advanced HCC. Patients received 750 mg/m2 capecitabine b.i.d. 14 days plus 800 mg of PHY906 b.i.d. on days 1–4 and days 8–11 every 21-day cycle. The primary endpoint was 6-month survival rate, and secondary endpoints were progression-free survival, overall survival, disease control rate, and safety. Results Thirty-nine subjects completed the study with a 46.2% stable disease rate. The median progression-free survival was 1.5 months, and median overall survival (mOS) was 6 months with a 51.3% 6-month survival rate. The most common adverse events included lower hemoglobin, diarrhea, pain, abdomen (not otherwise specified), fatigue, increased aspartate aminotransferase, and bilirubin. Patients who (a) had not received previous chemotherapies or targeted therapy or (b) had lower starting alpha-fetoprotein (AFP) levels or (c) had HBV infection showed better clinical outcome. Conclusion Our data showed that PHY906 increases the therapeutic index of capecitabine by enhancing its antitumor activity and reduces its toxicity profile in advanced HCC.

Dramatic advances in immune therapy have emerged as a promising strategy in cancer therapeutics. In addition to chemotherapy and radiotherapy, inhibitors targeting immune-checkpoint molecules such as cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death receptor-1 (PD-1) and its ligand (PD-L1) demonstrate impressive clinical benefits in clinical trials. In this review, we present background information about therapies involving PD-1/PD-L1 blockade and provide an overview of current clinical trials. Furthermore, we present recent advances involving predictive biomarkers associated with positive therapeutic outcomes in cancer immunotherapy.

Technology offers opportunities to revolutionize medicine and research but can threaten privacy and patient confidentiality. As the scale of patient data explodes, the safety and integrity of medical information are increasingly at stake. We highlight security and privacy issues associated with genomic research, medical devices, and wearable technology.

Purpose. This study aims to evaluate the prognostic value of human Mitotic Centromere-Associated Kinesin (MCAK), a microtubule-dependent molecular motor, in breast cancers. The posttranscriptional regulation of MCAK by microRNAs will also be explored.Methods. The large-scale gene expression datasets of breast cancer (total n=4,677) were obtained from GEO, NKI, and TCGA database. Kaplan-Meier and Cox analyses were used for survival analysis. MicroRNAs targeting MCAK were predicted by bioinformatic analysis and validated by a dual-luciferase reporter assay.Results. The expression of MCAK was significantly associated with aggressive features of breast cancer, including tumor stage, Elston grade, and molecular subtypes, for global gene expression datasets of breast cancer (pConclusion. MCAK could serve as a prognostic biomarker for breast cancers. miR-485-5p and miR-181c could specifically target and suppress the MCAK gene expression in breast cancer cells.

// Chien-Ju Lin 1 , Yi-Ling Lin 2 , Frank Luh 3 , Yun Yen 4, 5 , Ruei-Ming Chen 1, 2, 4, 6 1 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan 2 Brain Disease Research Center, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan 3 Sino-American Cancer Foundation, Temple City, California, USA 4 Comprehensive Cancer Center, Taipei Medical University, Taipei, Taiwan 5 Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 6 Anesthetics and Toxicology Research Center and Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan Correspondence to: Ruei-Ming Chen, email: rmchen@tmu.edu.tw Yun Yen, email: yyen@tmu.edu.tw Keywords: nanoparticle, malignant glioma, apoptosis, angiogenesis Received: March 01, 2016 Accepted: May 23, 2016 Published: June 7, 2016 ABSTRACT Malignant gliomas are difficult to treat in clinical practice. This study was aimed to investigate the preclinical efficacy of CRLX101, an investigational nanoparticle-drug conjugate developed by conjugating camptothecin (CPT) with cyclodextrin-polyethylene glycol, against gliomas. CPT fluorescence was detected across tight-junction barriers and in mouse plasma and brain. Following CRLX101 treatment, CPT was distributed in the cytoplasm of human U87 MG glioma cells. U87 MG cell viability was decreased by CRLX101 and CPT. Moreover, CRLX101 induced less cytotoxicity to human astrocytes compared to CPT. Exposure of U87 MG cells to CRLX101 induced G 2 /M cell cycle arrest and apoptosis. Administration of CRLX101 induced apoptosis in mice brain tumor tissues and prolonged the survival rate of mice. In addition, CRLX101 inhibited hypoxia and angiogenesis by suppressing the expression of carbonic anhydrase IX, vascular endothelial growth factor, and CD31 in tumor sections. Taken together, this preclinical study showed that CRLX101 possesses antitumor abilities by inducing cell cycle arrest and apoptosis in glioma cells and inhibiting tumor angiogenesis, thereby prolonging the lifespan of mice bearing intracranial gliomas. These data support further research of CRLX101 in patients with brain tumors.

Abnormal spindle-like microcephaly-associated (ASPM) protein is essential for mitotic spindle function during cell replication. The present study aimed to evaluate the hypothesis that ASPM serves a critical role in cancer invasiveness and may act as a prognostic biomarker in bladder cancer. In total, 6 independent worldwide bladder cancer microarray mRNA expression datasets (n=1,355) with clinical and follow-up annotations were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Reverse transcription-quantitative polymerase chain reaction analysis revealed that ASPM mRNA expression was higher in bladder cancer tissue compared with adjacent normal bladder mucosae in 10 paired human tissue samples (P=0.004). ASPM overexpression in human bladder cancer samples was consistent with the mRNA expression datasets from GEO and TCGA. Bioinformatics analysis indicated that ASPM mRNA expression was significantly associated with grade and tumor node metastasis (TNM) stage in bladder cancer, based on pooled GEO and TCGA datasets (P

Human intrahepatic cholangiocarcinomas are one of the most difficult cancers to treat. In our study, Lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme-CoA (HMG-CoA) reductase inhibitor, demonstrated anticancer properties by inhibiting cancer cell proliferation, cell migration and cell adhesion. Lovastatin inhibited the expressions of transforming growth factor (TGF)-β1, cyclooxygenase (COX)-2, and intercellular adhesion molecule (ICAM)-1. Furthermore, lovastatin inhibited the expressions of integrin β1 and integrin β3 but not integrin αv or integrin β5. While Lovastatin's inhibitory effects on TGFβ1, COX2, and ICAM-1 expression were independently controlled by the tumor suppressor LKB1, integrin β3 expression was not affected. Lovastatin's inhibitory effect on cell adhesion was associated with the decreased expression of integrin β3 and cell surface heterodimer integrin αvβ3. Quantitative real time PCR, fluorescent microscopy, and cell migration assays all confirmed that Lovastatin inhibits integrin αvβ3 downstream signaling including FAK activation, and β-catenin, vimentin, ZO-1, and β-actin. Overall, Lovastatin reduced tumor cell proliferation and migration by modifying the expression of genes involved in cell adhesion and other critical cellular processes. Our study highlights novel anti-cancer properties of Lovastatin and supports further exploration of statins in the context of cholangiocarcinoma therapy.

PURPOSE Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have shown that UCK2 is overexpressed in many types of cancer and may play a crucial role in activating antitumor prodrugs in human cancer cells. In the current study, we evaluated the potential prognostic value of UCK2 in breast cancer. METHODS We searched public databases to explore associations between UCK2 gene expression and clinical parameters in patients with breast cancer. Gene set enrichment analysis (GSEA) was performed to identify biological pathways associated with UCK2 gene expression levels. Survival analyses were performed using 10 independent large-scale breast cancer microarray datasets. RESULTS We found that UCK2 mRNA expression was elevated in breast cancer tissue compared with adjacent nontumorous tissue or breast tissue from healthy controls. High UCK2 levels were correlated with estrogen receptor negativity (p