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Huanhuan Ren, Jun Ma, Lingling Si, Boxue Ren, Xiaoyu Chen, Dan Wang, Wenjin Hao, Xuexi Tang, Defang Li, Qiusheng Zheng
Background Phytoestrogens has been proposed as a replaceable medicine for climacteric hormone replacement therapy, according to EP3138562, WO/2017/019213 and US5516528. However, recent studies showed that phytoestrogens might promote the proliferation of breast cancer cells and that is associated with their estrogenic activity. Acacetin, as one phytoestrogen, has been reported to exhibit estrogenic activity. But the effects of Acacetin on breast cancer cells proliferation have not been explored Objective In this study, we evaluated the effects of acacetin on breast cancer MCF-7 cells proliferation and explored its possible mechanism...
April 20, 2018: Recent Patents on Anti-cancer Drug Discovery
Annette Fenner
No abstract text is available yet for this article.
April 19, 2018: Nature Reviews. Urology
Marina Baretti, Dung T Le
Microsatellite instability (MSI) refers to the hypermutator phenotype secondary to frequent polymorphism in short repetitive DNA sequences and single nucleotide substitution, as consequence of DNA mismatch repair (MMR) deficiency. MSI secondary to germline mutation in DNA MMR proteins is the molecular fingerprint of Lynch Syndrome (LS), while epigenetic inactivation of these genes is more commonly found in sporadic MSI tumors. MSI occurs at different frequencies across malignancies, although original methods to assess MSI or MMR deficiency have been developed mostly in LS related cancers...
April 15, 2018: Pharmacology & Therapeutics
Franca Marino, Angela Scanzano, Laura Pulze, Monica Pinoli, Emanuela Rasini, Alessandra Luini, Raffaella Bombelli, Massimiliano Legnaro, Magda de Eguileor, Marco Cosentino
This study tests the hypothesis that in isolated human polymorphonuclear leukocytes (PMN) adrenergic ligands can affect neutrophil extracellular trap (NET) formation. We have previously shown that, in PMN, adrenaline (A), through the activation of adrenergic receptors (AR), reduces stimulus-dependent cell activation; we have, therefore, planned to investigate if AR are involved in NET production. PMN were obtained from venous blood of healthy subject. The ability of adrenergic ligands to affect reactive oxygen species (ROS) production, NET production, and cell migration was investigated in cells cultured under resting conditions or after activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP), LPS, or IL-8...
April 18, 2018: Journal of Leukocyte Biology
Hang Zheng, Hong Li, Wenbo Tan, Chunlin Xu, Lijuan Jia, Dandan Wang, Zhuanjian Li, Gunrong Sun, Xiangtao Kang, Fengbin Yan, Xiaojun Liu
The cathepsin E-A-like, also known as 'similar to nothepsin', is a new member of the aspartic protease family, which may take part in processing of egg yolk macromolecules, due to it was identified in the chicken egg-yolk. Previously, studies have suggested that the expression of cathepsin E-A-like increased gradually during sexual maturation of pullets, but the exact regulation mechanism is poorly understood. In this study, to gain insight into the function and regulation mechanism of the gene in egg-laying hen, we cloned the cathepsin E-A-like gene and evaluated its evolutionary origin by using both phylogenetic and syntenic methods...
March 2018: Journal of Genetics
Ashley Jaggi, Marcus Drake, Emad Siddiqui, Francis Fatoye
AIMS: Healthcare guidelines are an important vehicle in establishing up-to-date evidence based medicine (EBM) in clinical practice. Due to varying development processes, clinical guidelines created by different institutions can often contain contrasting recommendations. This can have implications for optimal and standardized patient care across management settings. METHODS: The similarities and differences of treatment recommendations made in the National Institute for Health and Care Excellence (NICE), The European Association of Urology (EAU), and the International Consultation on Continence (ICI) guidelines for neurogenic lower urinary tract dysfunction (NLUTD) were assessed...
April 17, 2018: Neurourology and Urodynamics
Darren J Thornbrugh, Scott G Leibowitz, Ryan A Hill, Marc H Weber, Zachary C Johnson, Anthony R Olsen, Joseph E Flotemersch, John L Stoddard, David V Peck
Watershed integrity is the capacity of a watershed to support and maintain the full range of ecological processes and functions essential to sustainability. Using information from EPA's StreamCat dataset, we calculated and mapped an Index of Watershed Integrity (IWI) for 2.6 million watersheds in the conterminous US with first-order approximations of relationships between stressors and six watershed functions: hydrologic regulation, regulation of water chemistry, sediment regulation, hydrologic connectivity, temperature regulation, and habitat provision...
February 1, 2018: Ecological Indicators
Zhihua Gong, Junying Chen, Jia-Nan Cheng, Chengdu Sun, Qingzhu Jia, Xinwei Diao, Bo Zhu
BACKGROUND: The benefits of immune checkpoint inhibitors for first-line treatment in patients with lung adenocarcinoma harboring EGFR mutations are unclear. The effects of ICIs depend on the tumor microenvironment (TME). Differences in TME properties between mutant and wild-type EGFR have not been fully characterized. PATIENTS AND METHODS: We collected 105 surgically resected (50 EGFR mutated and 55 EGFR wild-type), treatment-naïve lung adenocarcinoma tissues with clinical data to investigate the landscape and compartmentalization of tumor-infiltrating immune cells with respect to EGFR status by immunohistochemistry...
March 17, 2018: Clinical Lung Cancer
Phyu Synn Oo, Yuya Yamaguchi, Akira Sawaguchi, Myat Tin Htwe Kyaw, Narantsog Choijookhuu, Mohmand Noor Ali, Naparee Srisowanna, Shin-Ichiro Hino, Yoshitaka Hishikawa
Estrogen affects mitochondrial function in various tissues, but the precise mechanism remains unclear. We, therefore investigated the effect on estrogen-regulated mitochondrial morphology by dynamin-related protein 1 (Drp1) and its Ser616-phosphorylated derivative (pDrp1Ser616 ) are involved in mitochondrial fission. MCF7 human breast cancer cells were treated with 17β-estradiol (E2 ), an estrogen receptor (ER) α and β antagonist (ICI 182, 780), an ERα antagonist (MPP), and an ERβ antagonist (PHTPP) for 24 hr...
February 27, 2018: Acta Histochemica et Cytochemica
Kris Derks, Jacco L G Steenhuijsen, Hetty A van den Berg, Saskia Houterman, Jeltsje Cnossen, Paul van Haaren, Katrien De Jaeger
Purpose: The purpose of this study was to analyze the effect of 2D conventional brachytherapy (CBT) compared to 3D MRI-guided brachytherapy (IGBT) with and without the use of interstitial needles on local control, overall survival, and toxicity in patients treated for cervical cancer with radiation or chemoradiation. Material and methods: A retrospective analysis was performed of biopsy-proven FIGO IB-IVA cervical cancer patients, treated with primary radiation or chemoradiation, followed by brachytherapy (BT) between January 1997 and July 2016...
February 2018: Journal of Contemporary Brachytherapy
Gabriel O Eniafe, Damilohun S Metibemu, Olaposi I Omotuyi, Adewale J Ogunleye, Olumide K Inyang, Niyi S Adelakun, Yakubu O Adeniran, Bamidele Adewumi, Ojochenemi A Enejoh, Joseph O Osunmuyiwa, Sidiqat A Shodehinde, Oluwatoba E Oyeneyin
Asthma is an inflammatory disease of the airway that poses a major threat to human health. With increase industrialization in the developed and developing countries, the incidence of asthma is on the rise. The β2-adrenergic receptor is an important target in designing anti-asthmatic drugs. The synthetic agonists of the β2-adrenergic receptor used over the years proved effective, but with indispensable side effects, thereby limiting their therapeutic use on a long-term scale. Inverse agonists of this receptor, although initially contraindicated, had been reported to have long-term beneficial effects...
2018: Bioinformation
Rawad Elias, Anita Giobbie-Hurder, Nadine Jackson McCleary, Patrick Ott, F Stephen Hodi, Osama Rahma
BACKGROUND: Immune checkpoint inhibitors targeting PD-1/PD-L1 pathway demonstrated promising activities in variety of malignancies, however little is known regarding their efficacy in adults aged ≥65 years. METHODS: We conducted a systematic review and a study-level meta-analysis to explore efficacy of ICIs based on age, younger vs older than 65 years. We included in this analysis randomized controlled phase II or III studies in patients with metastatic solid tumors that compared efficacy of PD-1 or PD-L1 inhibitors to a non-PD-1/PD-L1 inhibitor...
April 4, 2018: Journal for Immunotherapy of Cancer
L Derosa, M D Hellmann, M Spaziano, D Halpenny, M Fidelle, H Rizvi, N Long, A J Plodkowski, K C Arbour, J E Chaft, J A Rouche, L Zitvogel, G Zalcman, L Albiges, B Escudier, B Routy
Background: The composition of gut microbiota affects anti-tumor immune responses, preclinical and clinical outcome following immune checkpoint inhibitors (ICI) in cancer. Antibiotics (ATB) alter gut microbiota diversity and composition leading to dysbiosis, which may affect effectiveness of ICI. Patients and Methods: We examined patients with advanced renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) treated with anti-PD-(L)1 mAb monotherapy or combination at two academic institutions...
March 30, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Brian S Miller, Elanor J Miller
The seasonal occupancy and diel behaviour of sperm whales (Physeter macrocephalus) was investigated using data from long-term acoustic recorders deployed off east Antarctica. An automated method for investigating acoustic presence of sperm whales was developed, characterised, and applied to multi-year acoustic datasets at three locations. Instead of focusing on the acoustic properties of detected clicks, the method relied solely on the inter-click-interval (ICI) for determining presence within an hour-long recording...
April 3, 2018: Scientific Reports
Daniel L Suzman, Lorraine Pelosof, Amy Rosenberg, Mark I Avigan
Immune checkpoint inhibitors (ICIs) block CTLA-4, PD-1, and PD-L1, or other molecules that control anti-tumor activities of lymphocytes. These products are associated with a broad array of immune-related toxicities affecting a variety of organs, including the liver. ICI-associated immune-mediated hepatitis (IMH) ranges in severity between mild and life-threatening and is marked by findings that bear both similarities as well as differences with idiopathic autoimmune hepatitis. Hepatotoxic events are often detected in clinical trials of ICIs that are powered for efficacy...
March 30, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Jan Krhut, Marcel Gärtner, Jan Mokris, Lukas Horcicka, Kamil Svabik, Roman Zachoval, Alois Martan, Peter Zvara
AIMS: While the effect of different types of incontinence on the quality of life (QoL) has been clearly documented, the information about the impact of incontinence severity on QoL in women is lacking. Therefore, we investigated whether increasingly severe degrees of incontinence were linearly correlated with poorer QoL. METHODS: We included 391 incontinent women and 81 continent volunteers in the study and assessed them in accordance with routine clinical practice...
March 31, 2018: Neurourology and Urodynamics
Yuko Kitawaki, Yasuhiro Nakamura, Fumie Kubota-Nakayama, Yuto Yamazaki, Yasuhiro Miki, Shuko Hata, Kazue Ise, Kumi Kikuchi, Ryo Morimoto, Fumitoshi Satoh, Hironobu Sasano
The tumor microenvironment plays pivotal roles in various human neoplasms. However, that of benign tumor, particularly hormone-secreting endocrine tumors, has remained virtually unknown. Therefore, we firstly attempted to analyze the tumor microenvironment of autonomous hormone-secreting adrenocortical adenomas. We first histologically evaluated 21 cortisol-producing adrenocortical adenoma (CPA) and 13 aldosterone-producing adrenocortical adenoma (APA) cases. Quantitative histological analysis revealed that intratumoral immune cell infiltration (ICI) was more pronounced in CPAs than APAs...
March 26, 2018: Human Pathology
Fatou Jallow, Jennifer L Brockman, Kyle T Helzer, Debra E Rugowski, Vincent Goffin, Elaine T Alarid, Linda A Schuler
Prolactin (PRL) and estrogen cooperate in lobuloalveolar development of the mammary gland and jointly regulate gene expression in breast cancer cells in vitro . Canonical PRL signaling activates STAT5A/B, homologous proteins that have different target genes and functions. Although STAT5A/B are important for physiological mammary function and tumor pathophysiology, little is known about regulation of their expression, particularly of STAT5B, and the consequences for hormone action. In this study, we examined the effect of two estrogenic ligands, 17 β -estradiol (E2) and the clinical antiestrogen, ICI182,780 (ICI, fulvestrant) on expression of STAT5 isoforms and resulting crosstalk with PRL in normal and tumor murine mammary epithelial cell lines...
March 1, 2018: Journal of the Endocrine Society
Pierluigi Bonomo, Isacco Desideri, Mauro Loi, Monica Mangoni, Mariangela Sottili, Livia Marrazzo, Cinzia Talamonti, Daniela Greto, Stefania Pallotta, Lorenzo Livi
Introduction and background: Head and neck squamous cell carcinoma (HNSCC) has been increasingly recognized as an immune suppressive malignancy. The efficacy of immune checkpoint inhibitors (ICI's) in the context of recurrent/metastatic (R/M) setting anticipates the possible integration of immunotherapy into the therapeutic armamentarium of locally advanced disease. Durvalumab (DUR) is a humanized monoclonal IgG1, anti-PD-L1 antibody with promising data in R/M HNSCC. The aim of our study is to test the antitumor activity of a combined regimen incorporating an immune checkpoint inhibitor into a conventional bio-radiation strategy for the cure of unfavorable locally advanced HNSCC...
February 2018: Clinical and translational radiation oncology
Rodolfo Chicas-Sett, Ignacio Morales-Orue, Delvys Rodriguez-Abreu, Pedro Lara-Jimenez
Background: In the last years, limited studies have described that radiotherapy could produce important distant responses in unirradiated sites, the so-called "abscopal effect". Recent evidence suggests that radiotherapy induces antigen release from tumor, in this way activating the immune system. However, radiotherapy alone is rarely enough to induce the systemic response requested for control of the metastases. With the advent of immunotherapy, the immune checkpoint inhibitors (ICI) have demonstrated impressive efficacy in various metastatic cancers...
February 2018: Clinical and Translational Radiation Oncology
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