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First-in-human clinical studies

Yixuan Zhang, Muhammad Hussain, Xiuqin Yang, Peng Chen, Yaping Tian, Hongwu Du
BACKGROUND: Sjögren's syndrome (SS) is a systemic and chronic autoimmune disorder that affects the exocrine glands, with massive autoantibody production. Although the pathogenesis of the disorder is incompletely understood, some studies have reported that anti-moesin antibodies have been detected in autoimmune diseases with which SS is closely associated. Nevertheless, little is known about moesin's potential involvement in SS. OBJECTIVE: This study aims to verify whether moesin is a specific autoantigen involved in Chinese Hans SS patients...
March 19, 2018: Protein and Peptide Letters
Shih-Fan Lai, Yu-Hsuan Chen, Tony Hsiang-Kuang Liang, Che-Yu Hsu, Huang-Chun Lien, Yen-Sen Lu, Chiun-Sheng Huang, Sung-Hsin Kuo
INTRODUCTION: Whole brain (WB) re-irradiation for breast cancer patients with progressive brain metastasis after first-course WB radiotherapy (WBRT) is controversial. In this study, we sought to investigate the association between the molecular sub-classifications and breast-specific Graded Prognostic Assessment (GPA, which includes the Karnofsky performance status, molecular subtypes, and age as its indices) and the outcomes of breast cancer patients who received WB re-irradiation. METHODS: Twenty-three breast cancer patients who received WB re-irradiation for relapsed and progressive intracranial lesions after first-course WBRT between 2004 and 2016 were retrospectively reviewed...
March 20, 2018: Journal of Neuro-oncology
Korbinian N Kropp, Stefanie Maurer, Kathrin Rothfelder, Bastian J Schmied, Kim L Clar, Moritz Schmidt, Benedikt Strunz, Hans-Georg Kopp, Alexander Steinle, Frank Grünebach, Susanne M Rittig, Helmut R Salih, Daniela Dörfel
The first therapeutic proteasome inhibitor bortezomib has clinical efficacy in mantle cell lymphoma (MCL) which resulted in its incorporation in treatment algorithms for this disease. Impairment of proteasomal function by bortezomib is mediated via inhibition of the 20S core particle. However, proteasome function can also be modified by targeting upstream components of the ubiquitin-proteasome system. Recently, b-AP15 has been identified as a small molecule achieving proteasome inhibition by targeting the deubiquitinase (DUB) activity of the 19S regulatory subunit and was found to inhibit cancer cell growth in preclinical analyses...
March 19, 2018: Cancer Immunology, Immunotherapy: CII
Yujia You, Xiaolong Liang, Tinghui Yin, Min Chen, Chen Qiu, Chuang Gao, Xiaoyou Wang, Yongjiang Mao, Enze Qu, Zhifei Dai, Rongqin Zheng
Photodynamic therapy (PDT) holds promise for focal therapy of prostate cancer (PCa). However, the therapeutic efficacy needs improvement, and further development of PDT for PCa has challenges, including uncertainty of photosensitizers (PSs) accumulation at the tumor site and difficulty in visualizing lesions using conventional ultrasound (US) imaging. We have developed novel porphyrin-grafted lipid (PGL) microbubbles (MBs; PGL-MBs) and propose a strategy to integrate PGL-MBs with US imaging to address these limitations and enhance PDT efficacy...
2018: Theranostics
Jimin Shi, Lingyun Zhang, Daibing Zhou, Jinguo Zhang, Qunbo Lin, Wencai Guan, Jihong Zhang, Weimin Ren, Guoxiong Xu
Ribosomal protein L10 (RPL10) is one of large ribosomal proteins and plays a role in Wilms' tumor and premature ovarian failure. However, the function of RPL10 in human epithelial ovarian cancer (EOC) remains unknown. The purpose of this study was to examine the expression level and function of RPL10 in EOC. RPL10 protein expression was detected by immunohistochemistry and Western blot. The association RPL10 expression with clinical features was analyzed. Loss-of-function and gain-of-function approaches were applied in cellular assays, including cell viability, migration, invasion, and apoptosis...
2018: Journal of Cancer
Xiu-Mei Li, Xue-Gang Luo, Jun-Fang He, Nan Wang, Hao Zhou, Pei-Long Yang, Tong-Cun Zhang
Hypericum ascyron L. (Great St. Johnswort), which belongs to the Hypericaceae family, has been used for the treatment of hematemesis, metrorrhagia, rheumatism, swelling, stomach ache, abscesses, dysentery and irregular menstruation for >2,000 years in China. The aim of the present study was to clarify the anticancer activity compounds from H. ascyron L. and the underlying molecular mechanism. Anticancer activity of H. ascyron L. extract was evaluated using an MTT assay. To confirm the anticancer mechanism of activity compounds, Hoechst 33258, Annexin V-fluorescein isothiocyanate/propidium iodide, 2',7'-dichlorodihydrofluorescein diacetate, rhodamine 123 staining and caspase-3 activity analysis were performed...
March 2018: Oncology Letters
Anthony J Mannion, Heather R Martin, Zeli Shen, Ellen M Buckley, JoAnn L Dzink-Fox, Alexis Garcia, Robert P Marini, Mary M Patterson, James G Fox
Non-human primates (NHPs) for biomedical research are commonly infected with Shigella spp. that can cause acute dysentery or chronic episodic diarrhea. These animals are often prophylactically and clinically treated with quinolone antibiotics to eradicate these possible infections. However, chromosomally- and plasmid-mediated antibiotic resistance has become an emerging concern for species in the family Enterobacteriaceae . In this study, five individual isolates of multi-drug resistant Shigella flexneri were isolated from the feces of three macaques...
2018: Frontiers in Microbiology
Dandan Zhao, Shaoqian Zhao, Xiao Wang, Mingbo Su, Wen Liu, Qinyun Ma, Jie Hong, Weiqiong Gu, Jingya Li, Ruixin Liu, Guang Ning, Jiqiu Wang, Yifei Zhang
The clinical application of dipeptidyl peptidase IV inhibitors (DPP4i) increasing active glucagon-like peptide-1 (AGLP-1) levels has been linked to pancreatitis, pancreatic tumors, and cardiovascular events. However, DPP4 mutations in humans or the long-term outcomes of high glucagon-like peptide-1 (GLP-1) level exposure have not been reported. A trio family with a proband showing an extremely high AGLP-1 level [defined here as hyperglipemia (hyper-glucagon-like peptide-1-emia)] were conducted whole-exome sequencing for potential pathogenic genetic defects...
2018: Frontiers in Endocrinology
Chenzhou Wu, John Gleysteen, Nutte Tarn Teraphongphom, Yi Li, Eben Rosenthal
Head and neck cancers become a severe threat to human's health nowadays and represent the sixth most common cancer worldwide. Surgery remains the first-line choice for head and neck cancer patients. Limited resectable tissue mass and complicated anatomy structures in the head and neck region put the surgeons in a dilemma between the extensive resection and a better quality of life for the patients. Early diagnosis and treatment of the pre-malignancies, as well as real-time in vivo detection of surgical margins during en bloc resection, could be leveraged to minimize the resection of normal tissues...
March 18, 2018: International Journal of Oral Science
Justin O Szot, Hartmut Cuny, Gillian M Blue, David T Humphreys, Eddie Ip, Katrina Harrison, Gary F Sholler, Eleni Giannoulatou, Paul Leo, Emma L Duncan, Duncan B Sparrow, Joshua W K Ho, Robert M Graham, Nicholas Pachter, Gavin Chapman, David S Winlaw, Sally L Dunwoodie
BACKGROUND: Congenital heart disease (CHD)-structural abnormalities of the heart that arise during embryonic development-is the most common inborn malformation, affecting ≤1% of the population. However, currently, only a minority of cases can be explained by genetic abnormalities. The goal of this study was to identify disease-causal genetic variants in 30 families affected by CHD. METHODS: Whole-exome sequencing was performed with the DNA of multiple family members...
March 2018: Circ Genom Precis Med
Chantal Beatrice Magne Nde, Gloria Casas Gimeno, Maria Docanto, Kevin C Knower, Morag J Young, Jakob Buehn, Edris Sayed, Colin D Clyne
Activation of oestrogen receptor α (ERα) stimulates cell division and tumour growth by modulating the expression of ERα target genes. This activation involves the recruitment of specific proteins with activities that are still not fully understood. Timeless, the human homologue of the Drosophila gene involved in circadian rhythm, was previously shown to be a strong predictor of tamoxifen relapse, and is involved in genomic stability and cell cycle control. In this study, we investigated the interplay between Timeless and ERα, and showed that human Timeless is an ERα coactivator...
March 16, 2018: Journal of Molecular Biology
Faisal E Al Jofi, Tao Ma, Dong Guo, Monica P Schneider, Yan Shu, Hockin H K Xu, Abraham Schneider
BACKGROUND: Compelling evidence indicates that metformin, a low-cost and safe orally administered biguanide prescribed to millions of type 2 diabetics worldwide, induces the osteoblastic differentiation of mesenchymal stromal cells (MSCs) through the 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway. As a highly hydrophilic cationic compound, metformin uptake is facilitated by cell membrane organic cation transporters (OCTs) of the solute carrier 22A gene family...
March 16, 2018: Cytotherapy
L Lecová, F Weisz, P Tůmová, V Tolarová, E Nohýnková
To date, genotyping data on giardiasis have not been available in the Czech Republic. In this study, we characterized 47 human isolates of Giardia intestinalis from symptomatic as well as asymptomatic giardiasis cases. Genomic DNA from trophozoites was tested by PCR-sequence analysis at three loci (β-giardin, glutamate dehydrogenase and triose phosphate isomerase). Sequence analysis showed assemblages A and B in 41 (87.2%) and six (12.8%) isolates, respectively. Two of the 41 assemblage A samples were genotyped as sub-assemblage AI, and 39 were genotyped as sub-assemblage AII...
March 20, 2018: Parasitology
Carole Mast, Dominique Dardevet, Isabelle Papet
The optimisation of nutritional support for the growing number of older individuals does not usually take into account medication. Paracetamol (acetaminophen; APAP) is the first intention treatment of chronic pain that is highly prevalent and persistent in the elderly. Detoxification of APAP occurs in the liver and utilises sulfate and glutathione (GSH), both of which are issued from cysteine (Cys), a conditionally indispensable amino acid. The detoxification-induced siphoning of Cys could reduce the availability of Cys for skeletal muscle...
March 20, 2018: Nutrition Research Reviews
Maria José Costa, Jyothirmayee Kudaravalli, Wen-Hui Liu, Jeffrey Stock, Sophanna Kong, Shu-Hui Liu
The development of therapeutic monoclonal antibodies through mouse immunization often originates drug candidates that are not cross-reactive to the mouse ortholog. In such cases, and particularly in oncology, drug efficacy studies are performed on human tumor xenografts or with "surrogate" anti-mouse ortholog antibodies if targeting tumor host cells. Safety assessment of drug candidate(s) is performed at a later development stage in healthy non-human primates. While the latter remains necessary before a drug advances into human subjects, it precludes evaluation of safety in disease conditions and drug de-risking during early development...
2018: PloS One
Clémence Granier, Emeline Vinatier, Elia Colin, Marion Mandavit, Charles Dariane, Virginie Verkarre, Lucie Biard, Rami El Zein, Corinne Lesaffre, Isabelle Galy-Fauroux, Hélène Roussel, Eléonore De Guillebon, Charlotte Blanc, Antonin Saldmann, Cécile Badoual, Alain Gey, Éric Tartour
Immune cells are important components of the tumor microenvironment and influence tumor growth and evolution at all stages of carcinogenesis. Notably, it is now well established that the immune infiltrate in human tumors can correlate with prognosis and response to therapy. The analysis of the immune infiltrate in the tumor microenvironment has become a major challenge for the classification of patients and the response to treatment. The co-expression of inhibitory receptors such as Program Cell Death Protein 1 (PD1; also known as CD279), Cytotoxic T Lymphocyte Associated Protein 4 (CTLA-4), T-Cell Immunoglobulin and Mucin Containing Protein-3 (Tim-3; also known as CD366), and Lymphocyte Activation Gene 3 (Lag-3; also known as CD223), is a hallmark of T cell exhaustion...
February 8, 2018: Journal of Visualized Experiments: JoVE
Maha Al-Faqawi, Yousef Abuowda, Alaa Eldeen Elmassry, Bettina Böttcher
BACKGROUND: The frequency and severity of chronic obstructive pulmonary disease (COPD) exacerbations are the most important determinants of prognosis in COPD. The aim of this study was to assess the management of patients presenting with COPD exacerbations at the Nasser Medical Complex in the Gaza Strip and to compare the management with the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD 2015). METHODS: We reviewed the medical records of all patients admitted to Nasser Medical Complex and diagnosed with COPD exacerbation between Jan 1, 2014, and Dec 31, 2016...
February 21, 2018: Lancet
Jannis Köhler, Jegor Ruschke, Katja Bettina Ferenz, Cemal Esen, Michael Kirsch, Andreas Ostendorf
Albumin-derived perfluorocarbon-based capsules are promising as artificial oxygen carriers with high solubility. However, these capsules have to be studied further to allow initial human clinical tests. The aim of this paper is to provide and characterize a holographic optical tweezer to enable contactless trapping and moving of individual capsules in an environment that mimics physiological (in vivo) conditions most effectively in order to learn more about the artificial oxygen carrier behavior in blood plasma without recourse to animal experiments...
February 1, 2018: Biomedical Optics Express
Zhenlei Li, Xiaoping Zou, Hao Zhu, Min Chen, Yan Zhao
Pancreatic cancer is an aggressive disease with a particularly poor prognosis contributing to a substantial percentage of cancer-associated mortality rates. In the present study, the combination treatment of baicalein (BAI) and gemcitabine (GEM) was investigated to examine whether it inhibited the growth of the human CFPAC-1 pancreatic cancer cell line in vitro and in vivo . The cytotoxic interactions between BAI and GEM in human pancreatic cancer cell lines were determined using MTT assays, and the effect of the two agents on apoptosis was detected using Hoechst 33258 staining and annexin V/7-AAD...
April 2018: Oncology Letters
Olivia Falconer, Marie-Louise Newell, Christine E Jones
The success of prevention of mother to child transmission programs over the last two decades has led to an increasing number of infants who are exposed to human immunodeficiency virus (HIV), but who are not themselves infected (HIV-exposed, uninfected infants). Although the morbidity and mortality among HIV-exposed, uninfected infants is considerably lower than that among HIV-infected infants, they may remain at increased risk of infections in the first 2 years of life compared with their HIV-unexposed peers, especially in the absence of breastfeeding...
2018: Frontiers in Immunology
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