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https://www.readbyqxmd.com/read/28647693/recognition-investigation-and-management-of-mitochondrial-disease
#1
REVIEW
James E Davison, Shamima Rahman
Mitochondria are dynamic organelles present in virtually all human cells that are needed for a multitude of cellular functions, including energy production, control of cell apoptosis and numerous biochemical catabolic and synthetic pathways that are critical for cellular health. Primary mitochondrial disorders are a group of greater than 200 single gene defects arising from two genomes (nuclear and mitochondrial) leading to mitochondrial dysfunction, and are associated with extremely heterogeneous phenotypes...
June 24, 2017: Archives of Disease in Childhood
https://www.readbyqxmd.com/read/28645940/t-cell-receptors-for-clinical-therapy-in-vitro-assessment-of-toxicity-risk
#2
Andre Kunert, Matthias Obenaus, Cor Hj Lamers, Thomas Blankenstein, Reno Debets
Adoptive therapy with T cell receptor (TCR)-engineered T cells has shown promising results in the treatment of patients with tumors, and the number of TCRs amenable for clinical testing is expanding rapidly. Notably, adoptive therapy with T cells is challenged by treatment-related side effects, which calls for cautious selection of target antigens and TCRs that goes beyond their mere ability to induce high T cell reactivity. Here, we propose a sequence of in vitro assays to improve selection of TCRs, and exemplify risk assessments of on-target as well as off-target toxicities using TCRs directed against Cancer Germline Antigens...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28642819/adoptive-cell-therapy-using-pd-1-myeloma-reactive-t-cells-eliminates-established-myeloma-in-mice
#3
Weiqing Jing, Jill A Gershan, Grace C Blitzer, Katie Palen, James Weber, Laura McOlash, Matthew Riese, Bryon D Johnson
BACKGROUND: Adoptive cellular therapy (ACT) with cancer antigen-reactive T cells following lymphodepletive pre-conditioning has emerged as a potentially curative therapy for patients with advanced cancers. However, identification and enrichment of appropriate T cell subsets for cancer eradication remains a major challenge for hematologic cancers. METHODS: PD-1(+) and PD-1(-) T cell subsets from myeloma-bearing mice were sorted and analyzed for myeloma reactivity in vitro...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28642198/treatment-of-intestinal-fibrosis-in-experimental-inflammatory-bowel-disease-by-the-pleiotropic-actions-of-a-local-rho-kinase-inhibitor
#4
Tom Holvoet, Sarah Devriese, Karolien Castermans, Sandro Boland, Dirk Leysen, Yves-Paul Vandewynckel, Lindsey Devisscher, Lien Van den Bossche, Sophie Van Welden, Melissa Dullaers, Roosmarijn E Vandenbroucke, Riet De Rycke, Karel Geboes, Arnaud Bourin, Olivier Defert, Pieter Hindryckx, Martine De Vos, Debby Laukens
BACKGROUND: Intestinal fibrosis resulting in (sub)obstruction is a common complication of Crohn's disease (CD). Rho kinases (ROCKs) play multiple roles in TGFβ1-induced myofibroblast activation that could be therapeutic targets. Because systemic ROCK inhibition causes cardiovascular side-effects, we evaluated the effects of a locally acting ROCK inhibitor (AMA0825) on intestinal fibrosis. METHODS: Fibrosis was assessed in mouse models using dextran sulfate sodium and adoptive T cell transfer...
June 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28641664/-research-progress-of-cell-immunotherapy-in-treatment-of-hematological-malignancies-review
#5
Wei Zhang, Hong-Mei Jing, Ji-Jun Wang, Xiao-Yan Ke
Cell immunotherapy, as an important mean of tumor therapy, infuses a large number of immune effector cells amplified in vitro to the patients, resulting in the anti-tumor effect. There have been a series techniques of cell immunotherapy, including T lymphocyte therapy, dendritic cell-based immune cell therapy, natural killer cell therapy, gamma delta T cell therapy and so on. The preparation and culture conditions, anti-tumor mechanism, target cells etc of these immune cells are not the same, the each with its advantages and disadvantages...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641533/role-and-therapeutic-potential-of-astrocytes-in-amyotrophic-lateral-sclerosis
#6
Mariana Pehar, Benjamin A Harlan, Kelby M Killoy, Marcelo R Vargas
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. The molecular mechanism underlying the progressive degeneration of motor neuron remains uncertain but involves a non-cell autonomous process. In acute injury or degenerative diseases astrocytes adopt a reactive phenotype known as astrogliosis. Astrogliosis is a complex remodeling of astrocyte biology and most likely represents a continuum of potential phenotypes that affect neuronal function and survival in an injury-specific manner...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28640782/perioperative-venous-thromboembolism-a-review
#7
Ronald J Gordon, Frederick W Lombard
Venous thromboembolism (VTE) is a significant problem in the perioperative period, increasing patient morbidity, mortality, and health care costs. It is also considered the most preventable of the major postoperative complications. Despite widespread adoption of prophylaxis guidelines, it appears that morbidity from the disease has not substantially changed within the past 2 decades. It is becoming clear that current prophylaxis efforts are not sufficient. Using more potent anticoagulants may decrease the incidence of VTE, but increase the risk for bleeding and infection...
June 20, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28639393/an-activatable-photosensitizer-targeted-to-%C3%AE-glutamyltranspeptidase
#8
Mayumi Chiba, Yuki Ichikawa, Mako Kamiya, Toru Komatsu, Tasuku Ueno, Kenjiro Hanaoka, Tetsuo Nagano, Norbert Lange, Yasuteru Urano
We adopted a spirocyclization-based strategy to design γ-glutamyl-hydroxymethyl selenorhodamine green (gGlu-HMSeR) as a photo-inactive compound that would be specifically cleaved by the tumor-associated enzyme γ-glutamyltranspeptidase (GGT) to generate a potent photosensitizer, HMSeR. gGlu-HMSeR takes a colorless, spirocyclic structure, and does not show marked phototoxicity to low-GGT-expressing cells or normal tissues upon irradiation with visible light. In contrast, HMSeR predominantly takes an open colored structure, and generates reactive oxygen species upon irradiation...
June 21, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28638729/cellular-immunotherapies-for-cancer
#9
REVIEW
Pedro Berraondo, Sara Labiano, Luna Minute, Iñaki Etxeberria, Marcos Vasquez, Alvaro Sanchez-Arraez, Alvaro Teijeira, Ignacio Melero
Lessons learned over decades on the use of gene and cell therapies have found clinical applicability in the field of cancer immunotherapy. On December 16(th), 2016 a symposium was held in Pamplona (Spain) to analyze and discuss the critical points for the clinical success of adoptive cell transfer strategies in cancer immunotherapy. Cellular immunotherapy is being currently exploited for the development of new cancer vaccines using ex vivo manipulated dendritic cells or to enhance the number of effector cells, transferring reinvigorated NK cells or T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637411/venom-peptides-and-toxins-a-prospective-spearhead-in-cancer-treatment
#10
Janet Pik Ching Wong, Bin Li, Hang Fai Kwok
Cancer is a condition of genetically or environmentally mutated, uncontrollable cell growth that directly affects human morbidity and mortality. Many treatments have been adopted to reduce cancer cell proliferation; however, new mutated developments of some cancer cells have started to show resistance towards current therapies and treatments that cause some drugs to lose their efficacy. Additionally, deleterious side-effects of some hard application methods like radiation therapy, chemotherapy, and surgery are less favorable...
June 21, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#11
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635517/a-primer-for-oncoimmunology-immunooncology
#12
Brad Bolon, Famke Aeffner
Oncoimmunology (or immunooncology) is a burgeoning specialty of precision ("personalized") medicine designed to heighten the antitumor response of the immune system against molecules expressed excessively or only by tumor cells. This focus is necessary, as cancers are polyclonal tissues comprised of antigenically heterogeneous cells, the exact composition of which is shaped by the balance between antitumor immunity and tumor-promoting inflammation. Key targets include enhancing immune system (especially T cell) reactivity, inhibiting immune checkpoints, and promoting tumor cytolysis...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28633756/immunotherapy-the-wave-of-the-future-in-bladder-cancer
#13
Daniel P Petrylak
Urothelial cell carcinoma (UC) is one of the most common cancers and one of the most deadly. Metastatic UC is particularly hard to treat, because it is typically diagnosed when patients are elderly and have medical comorbidities. Many patients with metastatic UC are unable to receive cisplatin-based chemotherapy, due to older age at diagnosis and comorbidities, and even when platinum chemotherapy can be administered, it has limited success in prolonging survival. Recently, improved understanding of molecular targets and immunologic characteristics of urothelial tumor cells has resulted in new therapeutic approaches that may help optimize first- and second-line therapy...
June 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28629762/targeting-the-tumor-and-its-associated-stroma-one-and-one-can-make-three-in-adoptive-t-cell-therapy-of-solid-tumors
#14
Anna Mondino, Gerlanda Vella, Laura Icardi
Adoptive T cell therapy (ACT) has become a promising immunotherapeutic option for cancer patients. The proof for ACT therapeutic efficacy was first obtained with allogenic T cells and then reproduced with T cells isolated from patients' tumor samples (i.e. tumor-infiltrating lymphocytes). It is now clear that specificity of ACT products can be educated by genetically engineering T cells with classical T Cell Receptors (TCR) or chimeric antigen receptors (CAR). To date a poor accessibility of the tumor mass and a hostile microenvironment, influenced by genetic and epigenetic instability, mainly limit ACT therapeutic efficacy in the case of solid tumors...
June 15, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28629761/cytokines-for-the-induction-of-antitumor-effectors-the-paradigm-of-cytokine-induced-killer-cik-cells
#15
Elisa Cappuzzello, Roberta Sommaggio, Paola Zanovello, Antonio Rosato
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells...
June 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28627347/-clinical-effect-of-pulmonary-rehabilitation-therapy-including-respiratory-exercise-and-vibration-expectoration-on-patients-with-pulmonary-infection-after-abdominal-surgery
#16
Zhou Zhou, Xiaotong Han, Fengling Ning, Hui Wen, Maiying Fan, Xia Yuan, Jieying Luo, Yi Zhang
OBJECTIVE: To investigate the clinical effect of pulmonary rehabilitation therapy including respiratory exercise and vibration expectoration on patients with pulmonary infection after abdominal surgery. METHODS: A retrospective case control study was conducted. Seventy-six patients with pulmonary infection after abdominal surgery admitted to the First Affiliated Hospital of Hunan Normal University from September 2015 to September 2016 were enrolled. According to whether accept the pulmonary rehabilitation therapy or not, the patients were divided into two groups...
March 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28626876/optical-molecular-imaging-guided-radiation-therapy-part-2-integrated-x-ray-and-fluorescence-molecular-tomography
#17
Junwei Shi, Thirupandiyur S Udayakumar, Zhiqun Wang, Nesrin Dogan, Alan Pollack, Yidong Yang
PURPOSE: Differentiating tumor from its surrounding soft tissues is challenging for x-ray computed tomography (CT). Fluorescence molecular tomography (FMT) can directly localize the internal tumors targeted with specific fluorescent probes. A FMT system was developed and integrated onto a CT guided irradiator to improve tumor localization for image guided radiation. METHODS: The FMT system was aligned orthogonal to the cone beam CT onboard our previously developed image guided small animal arc radiation treatment system (iSMAART)...
June 19, 2017: Medical Physics
https://www.readbyqxmd.com/read/28620603/advances-in-the-knowledge-about-kidney-decellularization-and-repopulation
#18
REVIEW
Afrânio Côgo Destefani, Gabriela Modenesi Sirtoli, Breno Valentim Nogueira
End-stage renal disease (ESRD) is characterized by the progressive deterioration of renal function that may compromise different tissues and organs. The major treatment indicated for patients with ESRD is kidney transplantation. However, the shortage of available organs, as well as the high rate of organ rejection, supports the need for new therapies. Thus, the implementation of tissue bioengineering to organ regeneration has emerged as an alternative to traditional organ transplantation. Decellularization of organs with chemical, physical, and/or biological agents generates natural scaffolds, which can serve as basis for tissue reconstruction...
2017: Frontiers in Bioengineering and Biotechnology
https://www.readbyqxmd.com/read/28616376/genome-editing-and-muscle-stem-cells-as-a-therapeutic-tool-for-muscular-dystrophies
#19
REVIEW
Veronica Pini, Jennifer E Morgan, Francesco Muntoni, Helen C O'Neill
PURPOSE OF REVIEW: Muscular dystrophies are a group of severe degenerative disorders characterized by muscle fiber degeneration and death. Therapies designed to restore muscle homeostasis and to replace dying fibers are being experimented, but none of those in clinical trials are suitable to permanently address individual gene mutation. The purpose of this review is to discuss genome editing tools such as CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated), which enable direct sequence alteration and could potentially be adopted to correct the genetic defect leading to muscle impairment...
2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28615711/identification-and-characterization-of-a-rich-population-of-cd34-mesenchymal-stem-stromal-cells-in-human-parotid-sublingual-and-submandibular-glands
#20
Padma Priya Togarrati, Robson T Sasaki, Mohamed Abdel-Mohsen, Nuntana Dinglasan, Xutao Deng, Shivani Desai, Elaine Emmerson, Elizabeth Yee, William R Ryan, Marcelo C P da Silva, Sarah M Knox, Satish K Pillai, Marcus O Muench
Mesenchymal stem/stromal cells (MSCs) play crucial roles in maintaining tissue homeostasis during physiological turnovers and injuries. Very little is known about the phenotype, distribution and molecular nature of MSCs in freshly isolated human salivary glands (SGs) as most reports have focused on the analysis of cultured MSCs. Our results demonstrate that the cell adhesion molecule CD34 was widely expressed by the MSCs of human major SGs, namely parotid (PAG), sublingual (SLG) and submandibular (SMG) glands...
June 14, 2017: Scientific Reports
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