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https://www.readbyqxmd.com/read/28434148/advancing-chimeric-antigen-receptor-t-cell-therapy-with-crispr-cas9
#1
REVIEW
Jiangtao Ren, Yangbing Zhao
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (CRISPR/Cas9) system, an RNA-guided DNA targeting technology, is triggering a revolution in the field of biology. CRISPR/Cas9 has demonstrated great potential for genetic manipulation. In this review, we discuss the current development of CRISPR/Cas9 technologies for therapeutic applications, especially chimeric antigen receptor (CAR) T cell-based adoptive immunotherapy. Different methods used to facilitate efficient CRISPR delivery and gene editing in T cells are compared...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28434032/diabetes-bone-and-glucose-lowering-agents-basic-biology
#2
REVIEW
Beata Lecka-Czernik
Skeletal fragility often accompanies diabetes and does not appear to correlate with low bone mass or trauma severity in individuals with diabetes. Instead (and in contrast to those with osteoporotic bone disease), bone remodelling and bone turnover are compromised in both type 1 and type 2 diabetes, contributing to defective bone material quality. This review is one of a pair discussing the relationship between diabetes, bone and glucose-lowering agents; an accompanying review is provided in this issue of Diabetologia by Ann Schwartz (DOI: 10...
April 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28433679/part-i-design-synthesis-and-biological-evaluation-of-novel-pyrazole-benzimidazole-conjugates-as-checkpoint-kinase-2-chk2-inhibitors-with-studying-their-activities-alone-and-in-combination-with-genotoxic-drugs
#3
Shadia A Galal, Ahmed S Abdelsamie, Samia A Shouman, Yasmin M Attia, Hamed I Ali, Ashraf Tabll, Reem El-Shenawy, Yasmine S El Abd, Mamdouh M Ali, Abeer E Mahmoud, Abeer H Abdel-Halim, Amal A Fyiad, Adel S Girgis, Hoda I El-Diwani
Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main enzymes that affect the cell cycle. 2-Biarylbenzimidazoles are potent selective class of Chk2 inhibitors; the structure-based design was applied to synthesize a new series of this class with replacing the lateral aryl group by substituted pyrazoles. Ten pyrazole-benzimidazole conjugates from the best fifty candidates according to docking programs have been subjected to chemical synthesis in this study. The activities of the conjugates 5-14 as checkpoint kinase inhibitors and as antitumor alone and in combination with genotoxic drugs were evaluated...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433665/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#4
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart Lung Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016 in Bethesda Maryland to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
April 19, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28433657/mir-938-promotes-colorectal-cancer-cell-proliferation-via-targeting-tumor-suppressor-phlpp2
#5
Chang-Feng Li, Yong-Chao Li, Jing-Peng Jin, Zhen-Kun Yan, Dan-Dan Li
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although the development of therapy approaches, the outcome of CRC patients still is poor, understanding the biological mechanism of CRC progression is critical to improve the treatment strategies. miRNAs regulate CRC progression, we found miR-938 was upregulated in CRC tissues and cells, MTT assay, colony formation assay and soft agar growth assay suggested miR-938 overexpression promoted CRC cell proliferation, miR-938 knockdown inhibited CRC cell proliferation...
April 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28433598/mir-590-5p-a-density-sensitive-microrna-inhibits-tumorigenesis-by-targeting-yap1-in-colorectal-cancer
#6
Chunlin Ou, Zhenqiang Sun, Xiayu Li, Xiaoling Li, Weiguo Ren, Zailong Qin, Xuemei Zhang, Weitang Yuan, Jia Wang, Wentao Yu, Shiwen Zhang, Qiu Peng, Qun Yan, Wei Xiong, Guiyuan Li, Jian Ma
YAP1, a transcription co-activator, mediates the biological functions of the Hippo pathway. YAP1 inactivation is involved in cell-cell contact inhibition. In various tumors, YAP1 is upregulated through multiple mechanisms, and it functions as an oncogene. Here, we provided evidence that YAP1 influenced multiple signaling pathways in colorectal cancer (CRC) cells. We reported that miR-590-5p directly targets YAP1 and inhibits tumorigenesis in CRC cells both in vitro and in vivo xenograft model. We analyzed different cell densities and found that increased density caused increased expression of miR-590-5p, and decreased expression of its precursors (pri- and pre-miR-590)...
April 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28433330/bivalent-rlp2086-trumenba%C3%A2-development-of-a-well-characterized-vaccine-through-commercialization
#7
Khurram Sunasara, John Cundy, Sriram Srinivasan, Brad Evans, Weiqiang Sun, Scott Cook, Eric Bortell, John Farley, Daniel Griffin, Michele Bailey Piatchek, Katherine Arch-Douglas
The phrase "Process is the Product" is often applied to biologics, including multicomponent vaccines composed of complex components that evade complete characterization. Vaccine production processes must be defined and locked early in the development cycle to ensure consistent quality of the vaccine throughout scale-up, clinical studies, and commercialization. This approach of front-loading the development work helped facilitate the accelerated approval of the Biologic License Application for the well-characterized vaccine bivalent rLP2086 (Trumenba®, Pfizer Inc) in 2014 under Breakthrough Therapy Designation...
April 19, 2017: Vaccine
https://www.readbyqxmd.com/read/28433198/tumor-promoting-role-of-anti-tumor-macrophages-in-tumor-microenvironment
#8
REVIEW
Kuntal Kanti Goswami, Tithi Ghosh, Sarbari Ghosh, Madhurima Sarkar, Anamika Bose, Rathindranath Baral
Recent advances in tumor biology demand detailed analysis of the complex interaction of tumor cells with their adjacent microenvironment (tumor stroma) to understand the various mechanisms involved in tumor growth and metastasis. Mononuclear phagocytes or macrophages, a type of innate immune cells, defend the organism against infection and injury. On the otherhand, tumor associated macrophages (TAMs) constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype...
April 13, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28433052/metabolomics-strategies-to-define-the-role-of-metabolism-in-virus-infection-and-pathogenesis
#9
Marianne Manchester, Anisha Anand
Metabolomics is an analytical profiling technique for measuring and comparing large numbers of metabolites present in biological samples. Combining high-throughput analytical chemistry and multivariate data analysis, metabolomics offers a window on metabolic mechanisms. Because they intimately utilize and often rewire host metabolism, viruses are an excellent choice to study by metabolomics techniques. Studies of the effects of viruses on metabolism during replication in vitro and infection in animal models or human subjects have provided novel insights into these networks and provided new targets for therapy and biomarker development...
2017: Advances in Virus Research
https://www.readbyqxmd.com/read/28432682/prognostics-factors-and-survival-in-acral-lentiginous-melanoma
#10
M M Asgari, L Shen, M M Sokil, I Yeh, E Jorgenson
BACKGROUND: Acral lentiginous melanoma is a rare melanoma subtype that disproportionately afflicts people of color. Acral lentiginous melanomas have a worse prognosis than other melanomas subtypes, which has been attributed to aggressive biological behavior, more advanced stage at presentation and possible disparities in access to healthcare. OBJECTIVES: Using comprehensive patient data and long-term follow-up information in a well-characterized cohort, to examine how patient, tumor, and clinical management variables impact overall and melanoma-specific survival...
April 22, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28432648/rationale-for-new-checkpoint-inhibitor-combinations-in-melanoma-therapy
#11
Mario Mandalà, Carlo Tondini, Barbara Merelli, Daniela Massi
The use of monoclonal antibodies that block immunologic checkpoints, which mediate adaptive immune resistance, has revolutionized the treatment of metastatic melanoma patients. Specifically, targeting single immune suppressive molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or programmed cell death protein 1 (PD-1) expressed on T cells or its primary ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical benefit for a subset of melanoma patients. Although single-agent immune checkpoint inhibitor therapy has demonstrated promising clinical activity in metastatic melanoma patients, there is still a significant proportion of patients who show primary resistance to these therapies...
April 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28432529/ginseng-derived-panaxadiol-saponins-promote-hematopoiesis-recovery-in-cyclophosphamide-induced-myelosuppressive-mice-potential-novel-treatment-of-chemotherapy-induced-cytopenias
#12
Xin Sun, Yan-Na Zhao, Song Qian, Rui-Lan Gao, Li-Ming Yin, Li-Pei Wang, Beng-Hock Chong, Su-Zhan Zhang
OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C), a biologically active fraction isolated from total ginsenosides, to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide (CTX). METHODS: Mice with myelosuppression induced by CTX were treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80 mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC), neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony formation were observed, the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot...
April 22, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28432476/immunological-mechanisms-of-adsorptive-cytapheresis-in-inflammatory-bowel-disease
#13
REVIEW
Esteban Sáez-González, Inés Moret, Diego Alvarez-Sotomayor, Francia Carolina Díaz-Jaime, Elena Cerrillo, Marisa Iborra, Pilar Nos, Belén Beltrán
Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). The study of immunological pathways involved in the onset of IBD is of fundamental importance to identify potential biological markers of disease activity and specific targets for therapy. Removing excess and activated circulating leukocytes with adsorptive cytapheresis has been shown to be a potentially effective treatment for patients with an inflamed bowel. Adsorptive cytapheresis is a non-pharmacological approach for active IBD, in which known sources of inflammatory cytokines such as activated myeloid lineage leucocytes are selectively depleted from the circulatory system...
April 21, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28432472/anti-infective-and-anti-inflammatory-pharmacotherapies
#14
Mark I Rosenblatt
Ocular infection and inflammation are common and are associated with myriad ocular conditions ranging from mild disease to blinding conditions. There are numerous anti-invectives with spectra against inciting pathogens. Given the potential for ocular infections to rapidly progress initial broad spectrum therapy is usually required, with therapy tailored as microbiological identification and sensitivities become available. The emergence of antibiotic resistance has become a major health problem. Anti-inflammatory therapy can be institutes to prevent ocular symptoms and end-organ damage...
April 22, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28432221/biological-considerations-of-plasma-derived-and-recombinant-factor-viii-immunogenicity
#15
Jesse Lai, Christine Hough, Julie Tarrant, David Lillicrap
In hemophilia A, the most severe complication of factor VIII (FVIII) replacement therapy involves the formation of FVIII neutralizing antibodies, also known as inhibitors, in 25-30% of patients. This adverse event is associated with a significant increase in morbidity and economic burden, thus highlighting the need to identify methods to limit FVIII immunogenicity. Inhibitor development is regulated by a complex balance of genetic factors, such as FVIII genotype, and environmental variables, such as coexistent inflammation...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28431485/efficacy-of-golimumab-in-belgian-patients-with-active-rheumatoid-arthritis-despite-treatment-with-non-biologic-disease-modifying-anti-rheumatic-drugs-sub-analysis-of-the-go-more-study
#16
Patrick Durez, Marie Vanthuyne, Muhammad S Soyfoo, Ilse Hoffman, Michel Malaise, Piet Geusens
OBJECTIVES: The GO-MORE trial (NCT00975130) was a phase 3 study in 40 countries evaluating the efficacy and safety of golimumab as add-on therapy in biologic-naïve adults with active rheumatoid arthritis despite stable treatment with disease-modifying anti-rheumatic drugs. To inform local practice in Belgium and examine the role of baseline disease activity in treatment response, we compared the efficacy of golimumab in the Belgian subpopulation and the rest of the world. METHODS: Baseline disease activity and six-month efficacy rates in the GO-MORE trial were compared for the Belgian subpopulation and the rest of the world by t-tests and chi-squared tests...
April 21, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28431482/nanozyme-applications-in-biology-and-medicine-an-overview
#17
Jafar Golchin, Kazem Golchin, Neda Alidadian, Shahrooz Ghaderi, Sajjad Eslamkhah, Masoud Eslamkhah, Abolfazl Akbarzadeh
Nanozymes, in nature, are artificial enzymes. Innovated by Ronald Breslow to mimic enzymes. Nanozymes have widespread applications including targeted cancer therapy, diagnostic medicine and bio-sensing even environmental toxicology. However, these applications are a novel research field in biomedicine, but are growing fast. Enzyme-based applications such as immune-absorbent assay (ELIZA) are expensive because of the complexity of producing enzymes and antibodies. Not only, some nanoparticles can mimic these enzymes such as superoxides, but also they can manipulate biological pathways directly like autophagy...
April 21, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28431353/discovery-of-potential-anticancer-multi-targeted-ligustrazine-based-cyclohexanone-and-oxime-analogs-overcoming-the-cancer-multidrug-resistance
#18
Gao-Feng Zha, Hua-Li Qin, Bahaa G M Youssif, Muhammad Wahab Amjad, Maria Abdul Ghafoor Raja, Ahmed H Abdelazeem, Syed Nasir Abbas Bukhari
The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor. The current study comprises the synthesis of 34 novel ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes. The growth of 5 various cancer cell types was strongly inhibited by ligustrazine-containing oximes as revealed by biological evaluation...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430865/unmet-needs-in-the-first-line-treatment-of-follicular-lymphoma
#19
C Casulo, L Nastoupil, N H Fowler, J W Friedberg, C R Flowers
For the majority of patients with newly diagnosed follicular lymphoma (FL), current treatments, while not curative, allow for long remission durations. However, several important needs remain unaddressed. Studies have consistently shown that approximately 20% of patients with FL experience disease progression within 2 years of first-line treatment, and consequently have a 50% risk of death in 5 years. Better characterization of this group of patients at diagnosis may provide insight into those in need of alternate or intensive therapies, facilitate a precision approach to inform clinical trials, and allow for improved patient counseling...
April 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28430386/peptidome-analysis-of-human-serum-from-normal-and-preeclamptic-pregnancies
#20
Xiaonan Dai, Xuejing Song, Can Rui, Li Meng, Xuan Xue, Hongjuan Ding, Rong Shen, Jun Li, Jingyun Li, Yuanqing Lu, Wei Long
Preeclampsia is a kind of disease that severely harms the health of pregnant women and infants. To better understand the molecular mechanisms involved in preeclampsia, we used liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) to construct a comparative peptidomic profiling of human serum between normal and preeclamptic pregnancies. A total of 201 peptides were confidently identified, with 21 up-regulated and 3 down-regulated. Further analysis indicated that these differentially expressed peptides correlate with enzyme regulator activity, biological regulation, and coagulation cascades occurring during pathological changes of preeclampsia...
April 21, 2017: Journal of Cellular Biochemistry
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