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https://www.readbyqxmd.com/read/30110720/unleashing-the-therapeutic-potential-of-car-t-cell-therapy-using-gene-editing-technologies
#1
In-Young Jung, Jungmin Lee
Chimeric antigen receptor (CAR) T-cell therapy, an emerging immunotherapy, has demonstrated promising clinical results in hematological malignancies including B-cell malignancies. However, accessibility to this transformative medicine is highly limited due to the complex process of manufacturing, limited options for target antigens, and insufficient anti-tumor responses against solid tumors. Advances in gene-editing technologies, such as the development of Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9), have provided novel engineering strategies to address these limitations...
August 14, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/30110680/serum-creatinine-and-chronic-kidney-disease-epidemiology-estimated-glomerular-filtration-rate-independent-predictors-of-renal-replacement-therapy-following-cardiac-surgery
#2
George Drosos, Fotini Ampatzidou, Pantelis Sarafidis, Theodoros Karaiskos, Athanasios Madesis, Afroditi K Boutou
BACKGROUND: Most studies evaluating predictors of renal replacement therapy (RRT) following cardiac surgery use arbitrary defined limits of preoperative serum creatinine. The aim of this study was to evaluate the effect of preoperative renal function using either estimated-glomerular filtration rate (eGFR) derived using Chronic Kidney Disease-Epidemiology (CKD-EPI) or serum creatinine alone as a predictor for RRT after cardiac surgery. METHODS: In this prospective cohort study, baseline, intraoperative, and postoperative data of all patients who underwent an elective, urgent, or emergency cardiac surgery between 2012 and 2016 in a single center were analyzed in order to identify multivariate parameters determining the need for RRT after surgery...
August 15, 2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/30110678/heparg-progenitor-cell-derived-hepatocytes-cultured-in-bioartificial-livers-are-protected-from-healthy-and-acute-liver-failure-plasma-induced-toxicity
#3
Martien van Wenum, Philipp Treskes, Aziza A A Adam, Vincent A van der Mark, Aldo Jongejan, Perry D Moerland, Thomas M van Gulik, Ronald P J Oude Elferink, Robert A F M Chamuleau, Ruurdtje Hoekstra
BACKGROUND/AIMS: For applicability of cell-based therapies aimed at the treatment of liver failure, such as bioartificial livers (BALs) and hepatocyte transplantation, it is essential that the applied hepatocytes tolerate exposure to the patient plasma. However, plasma from both healthy donors and acute liver failure (ALF) patients is detrimental to hepatocytes and hepatic cell lines, such as HepaRG. We aimed to elucidate the underlying mechanisms of plasma-induced toxicity against HepaRG cells in order to ultimately develop methods to reduce this toxicity and render HepaRG-BAL treatment more effective...
August 15, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30110670/when-to-stop-eculizumab-in-complement-mediated-thrombotic-microangiopathies
#4
Sven R Olson, Eric Lu, Emilio Sulpizio, Joseph J Shatzel, Jose F Rueda, Thomas G DeLoughery
The terminal complement-inhibitor eculizumab has dramatically changed the management of patients with atypical hemolytic uremic syndrome (aHUS), and has also shown promise for treating certain forms of secondary HUS (sHUS), including that caused by drugs and solid-organ/hematopoietic stem cell transplant. While effective, eculizumab is costly and inconvenient. In this review, we evaluate the literature on eculizumab cessation in these diseases to better inform clinicians who consider stopping therapy. Reported relapse rates in aHUS after stopping eculizumab are as high as 30%, suggesting indefinite therapy is reasonable and that patients who choose to stop should be closely monitored...
August 15, 2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/30110590/pd-1-inhibitor-therapy-in-adult-t-cell-leukemia-lymphoma
#5
(no author information available yet)
New England Journal of Medicine, Volume 379, Issue 7, Page 695-697, August 2018.
August 16, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/30110577/new-cell-cycle-inhibitors-target-aneuploidy-in-cancer-therapy
#6
Masanori Kawakami, Xi Liu, Ethan Dmitrovsky
Aneuploidy is a hallmark of cancer. Defects in chromosome segregation result in aneuploidy. Multiple pathways are engaged in this process, including errors in kinetochore-microtubule attachments, supernumerary centrosomes, spindle assembly checkpoint (SAC) defects, and chromosome cohesion defects. Although aneuploidy provides an adaptation and proliferative advantage in affected cells, excessive aneuploidy beyond a critical level can be lethal to cancer cells. Given this, enhanced chromosome missegregation is hypothesized to limit survival of aneuploid cancer cells, especially when compared to diploid cells...
August 15, 2018: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/30110551/sialic-acid-anchored-micelles-a-hierarchical-targeting-device-for-enhanced-tumor-tissue-accumulation-and-cellular-internalization
#7
Meng-Lu Zhu, Xiao-Ling Xu, Xiao-Juan Wang, Nan-Nan Zhang, Kong-Jun Lu, Jing Qi, Fei-Yang Jin, Di Liu, Yong-Zhong Du
Targeted Drug Delivery Systems (TDDS) have attracted wide attention with reduced drug side effects and improved anti-tumor efficacy in comparison with traditional preparations. While targeting moiety in existing TDDS principally focused on recognition of receptors on the surface of tumor cells, accumulation into tumor tissue only could be performed by enhanced permeability and retention effect and active transportation into tumor cells. Doxorubicin (DOX)-loaded sialic acid-dextran (Dex)-octadecanoic acid (OA) micelles (SA-Dex-OA/DOX) were designed for targeting hepatocellular carcinoma effectively...
August 15, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/30110158/tunability-of-biodegradable-poly-amine-co-ester-polymers-for-customized-nucleic-acid-delivery-and-other-biomedical-applications
#8
Amy C Kauffman, Alexandra S Piotrowski-Daspit, Kay H Nakazawa, Yuhang Jiang, Amit Datye, W Mark Saltzman
Gene therapy promises to treat diseases that arise from genetic abnormalities by correcting the underlying cause of the disease rather than treating the associated symptoms. Successful transfer of nucleic acids into cells requires efficient delivery vehicles that protect the cargo and can penetrate the appropriate cellular barriers before releasing their contents. Many viral vectors and synthetic polycationic vectors for nucleic acid delivery do not translate well from in vitro to in vivo applications due to their instability and toxicity...
August 15, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/30110119/intrapericardial-cisplatin-combined-with-oral-colchicine-resulted-in-long-term-control-of-malignant-pericardial-effusion-in-the-course-of-metastatic-renal-cancer
#9
Małgorzata Dybowska, Monika Szturmowicz, Paweł Kuca, Barbara Kazanecka, Janusz Burakowski, Cezary Czajka, Franciszek Grzegorczyk, Renata Langfort, Barbara Burakowska, Piotr Rudziński, Witold Tomkowski
Background Neoplastic pericardial effusion (NPE) represents a common cause of morbidity and mortality in patient with cancer. NPE presents frequently as cardiac tamponade, requiring urgent pericardiocentesis or pericardiotomy, with subsequent pericardial fluid drainage. Despite high effectiveness of such procedures, the recurrence of effusion is noted in 30- 60% of patients. Intrapericardial therapy with cisplatin was found to be effective in NPE due to lung and breast cancer. Its role in cardiac tamponade due to renal cancer is unknown...
August 15, 2018: Advances in Respiratory Medicine
https://www.readbyqxmd.com/read/30110025/enzyme-triggered-self-assembly-of-gold-nanoparticles-for-enhanced-retention-effects-and-photothermal-therapy-of-prostate-cancer
#10
Shuyan Yang, Defan Yao, Yanshu Wang, Weitao Yang, Bingbo Zhang, Dengbin Wang
A peptide-modified gold nanoparticle was developed for tumour-targeted therapy. Triggered by alkaline phosphatase, the CREKA-YPFFK(Nph) peptide can self-assemble and further result in accumulation of gold nanoparticles in tumour cells. The large-sized gold nanoparticle aggregates cannot escape from the tumour tissue, therefore realizing the goal of tumour-specific targeting, enhanced retention and photothermal effects.
August 15, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/30109911/the-next-generation-of-anticancer-metallopharmaceuticals-cancer-stem-cell-active-inorganics
#11
Kristine Laws, Kogularamanan Suntharalingam
Cancer stem cells (CSCs) are heavily linked to fatal incidences of cancer relapse and metastasis. Conventional cancer therapies such as surgery, chemotherapy, and radiation are largely futile against CSCs. Therefore, highly original approaches are needed to overcome CSCs and provide durable, long-term clinical outcomes. Many academia- and pharmaceutical-led studies aimed at developing chemical or biological anti-CSC agents are ongoing, however, the application of inorganic compounds is rare. In this minireview we discuss how the chemical diversity and versatility offered by metals has been harnessed to develop an unprecedented, emerging class of metallopharmaceuticals; CSC-active inorganics...
August 15, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/30109822/monogenic-intestinal-epithelium-defects-and-the-development-of-inflammatory-bowel-disease
#12
Gabriella Leung, Aleixo M Muise
The incidence of inflammatory bowel disease (IBD) is increasing worldwide, most notably in young children. The development of disease is a combination of several factors, including genetics, environment, the microbiota, and immune system. Recently, next-generation sequencing has allowed for the identification of novel genetic causes for intestinal disease, including pediatric inflammatory bowel disease (IBD). These IBD genes can generally be grouped into genes causing either primary immunodeficiency or intestinal epithelial defects (the focus of this review)...
September 1, 2018: Physiology
https://www.readbyqxmd.com/read/30109780/apatinib-targets-both-tumor-and-endothelial-cells-in-hepatocellular-carcinoma
#13
Chaoxu Yang, Shukui Qin
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignancies worldwide with poor prognosis and tends to be hypervascular. Aberrant expression of the vascular endothelial growth factor 2 (VEGFR-2) has been implicated in the progression of HCC and represents a valid target for anticancer therapy. Apatinib, a small molecule inhibitor of VEGFR-2 tyrosine kinase, shows strong antitumor activity in various tumors. This study is designed to evaluate the activity of apatinib on both human umbilical vein vascular endothelial cells (HUVECs) and HCC cell lines (in vitro and in vivo), and also to investigate the characteristics and possible mechanisms underlying these effects by molecular biology methods...
August 14, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/30109743/current-natural-therapies-in-the-treatment-against-glioblastoma
#14
REVIEW
José Ignacio Erices, Ángelo Torres, Ignacio Niechi, Isabel Bernales, Claudia Quezada
Glioblastoma (GBM) is the most common and aggressive brain tumor, which causes the highest number of deaths worldwide. It is a highly vascularized tumor, infiltrative, and its tumorigenic capacity is exacerbated. All these hallmarks are therapeutic targets in GBM treatment, including surgical removal followed by radiotherapy and chemotherapy. Current therapies have not been sufficient for the effective patient's management, so the classic therapies have had to expand and incorporate new alternative treatments, including natural compounds...
August 15, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/30109642/cannabinoid-based-therapies-and-brain-development-potential-harmful-effect-of-early-modulation-of-the-endocannabinoid-system
#15
Patrícia Schonhofen, Ivi Juliana Bristot, José Alexandre Crippa, Jaime Eduardo Cecílio Hallak, Antônio Waldo Zuardi, Richard B Parsons, Fábio Klamt
The endocannabinoid retrograde signaling pathway is widely expressed in the central nervous system, where it plays major roles in regulating synaptic plasticity (excitatory and inhibitory) through long-term potentiation and long-term depression. The endocannabinoid system (ECS) components-cannabinoid receptors, endocannabinoids and synthesis/degradation enzymes-are expressed and are functional from early developmental stages and throughout adolescent cortical development, regulating progenitor cell fate, neural differentiation, migration and survival...
August 14, 2018: CNS Drugs
https://www.readbyqxmd.com/read/30109601/common-genetic-variants-link-the-abnormalities-in-the-gut-brain-axis-in-prematurity-and-autism
#16
REVIEW
Elżbieta M Sajdel-Sulkowska, Monika Makowska-Zubrycka, Katarzyna Czarzasta, Kaja Kasarello, Vishal Aggarwal, Michał Bialy, Ewa Szczepanska-Sadowska, Agnieszka Cudnoch-Jedrzejewska
This review considers a link between prematurity and autism by comparing symptoms, physiological abnormalities, and behavior. It focuses on the bidirectional signaling between the microbiota and the brain, here defined as the microbiota-gut-vagus-heart-brain (MGVHB) axis and its systemic disruption accompanying altered neurodevelopment. Data derived from clinical and animal studies document increased prevalence of gastrointestinal, cardiovascular, cognitive, and behavioral symptoms in both premature and autistic children and suggest an incomplete maturation of the gut-blood barrier resulting in a "leaky gut," dysbiosis, abnormalities in vagal regulation of the heart, altered development of specific brain regions, and behavior...
August 14, 2018: Cerebellum
https://www.readbyqxmd.com/read/30109574/bioactivity-evaluations-of-betulin-identified-from-the-bark-of-betula-platyphylla-var-japonica-for-cancer-therapy
#17
Hae Min So, Hee Jeong Eom, Dahae Lee, Sil Kim, Ki Sung Kang, Il Kyun Lee, Kwan-Hyuck Baek, Jun Yeon Park, Ki Hyun Kim
Identification of bioactive natural products with anticancer activity as well as alleviating effects on chemotherapy-induced side effects has significant implications for cancer treatment. Betula platyphylla var. japonica, commonly known as Asian white birch, has been used in Chinese traditional medicine for a variety of purposes. In this study, the medicinal properties of betulin from B. platyphylla var. japonica useful for cancer management were investigated. LC/MS analysis revealed that betulin is a main chemical component of the EtOH extract of B...
August 14, 2018: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/30109544/phase-ii-feasibility-study-of-preoperative-concurrent-chemoradiotherapy-with-cisplatin-plus-5-fluorouracil-and-elective-lymph-node-irradiation-for-clinical-stage-ii-iii-esophageal-squamous-cell-carcinoma
#18
Jun Hashimoto, Ken Kato, Yoshinori Ito, Takashi Kojima, Tetsuo Akimoto, Hiroyuki Daiko, Yasuo Hamamoto, Hisayuki Matsushita, Susumu Katano, Hiroki Hara, Yoichi Tanaka, Yoshihiro Saito, Kengo Nagashima, Hiroyasu Igaki
BACKGROUND: Preoperative chemoradiotherapy (CRT) is a standard treatment for stage II/III esophageal cancer. Preoperative chemotherapy is also considered a standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in patients who undergo radical lymph node dissection. We conducted a feasibility study of preoperative CRT with cisplatin plus 5-fluorouracil (CF) and elective lymph node irradiation followed by esophagectomy with radical lymph node dissection in patients with stage II/III ESCC...
August 14, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/30109543/prognostic-significance-of-neutrophil-lymphocyte-ratio-nlr-and-correlation-with-pet-ct-metabolic-parameters-in-small-cell-lung-cancer-sclc
#19
Cem Mirili, Isa Burak Guney, Semra Paydas, Gulsah Seydaoglu, Tuba Korkmaz Kapukaya, Ali Ogul, Serkan Gokcay, Mahmut Buyuksimsek, Abdullah Evren Yetisir, Bilgin Karaalioglu, Mert Tohumcuoglu
PURPOSE: The aim of this study is to detect the prognostic significance of neutrophil/lymphocyte ratio (NLR) in SCLC and to evaluate the relation with 18F-FDG PET-CT metabolic parameters (PET-CT MPs). METHODS: Demographic parameters, laboratory values including NLR and other clinical variables were analyzed in 112 patients with small cell lung cancer (SCLC) and 54 of these patients had results of metabolic parameters detected with 18 FDG PET-CT [including SUVmax , SUVmean , metabolic tumor volume (MTV), whole body MTV (WBMTV), TLG (total lesion glycolysis), whole body TLG (WBTLG)] were evaluated for survival analyses...
August 14, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/30109514/rheumatic-manifestations-of-haemoglobinopathies
#20
REVIEW
Michael Hughes
PURPOSE OF THE REVIEW: To provide a clinically useful literature review on the rheumatic manifestations of haemoglobinopathies, critically analysing the literature from the past 5 years. RECENT FINDINGS: There are limited new data to guide the management of rheumatic manifestations of haemoglobinopathies. Data further confirm the wide spectrum of potential rheumatic/MSK involvement in haemoglobinopathies, which poses both a diagnostic and therapeutic challenge...
August 14, 2018: Current Rheumatology Reports
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