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https://www.readbyqxmd.com/read/28550802/mechanism-of-action-of-three-newly-registered-drugs-for-multiple-sclerosis-treatment
#1
REVIEW
Kaja Kasarełło, Agnieszka Cudnoch-Jędrzejewska, Andrzej Członkowski, Dagmara Mirowska-Guzel
Multiple sclerosis (MS) is a disease of suspected autoimmune origin leading to neurodegeneration. The disease pathomechanism is considered to be primarily based on neuroinflammation directed against myelin antigens caused by autoreactive T cells. MS etiology remains still unknown, which makes it difficult to create an efficient therapy, therefore, MS treatment targets mechanisms involved in disease pathology. In this review, we present the mechanism of action of three newly registered drugs for MS. Dimethyl fumarate (DMF) is an agent presenting a broad spectrum of action...
February 22, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28550507/histopathologic-features-are-more-important-prognostic-factors-than-primary-tumour-location-in-gastro-oesophageal-adenocarcinoma-treated-with-preoperative-chemoradiation-and-surgery
#2
Milan Vošmik, Jan Laco, Igor Sirák, Josef Dvořák, Petr Lochman, Miroslav Hodek, Petra Malá, Stanislav Rejchrt, Rudolf Repák, Michal Leško, Alexander Ferko, Aleš Ryška, Bohuslav Melichar, Jiří Petera
The aim of present study was to evaluate the impact of primary tumour location and other factors on the outcome of preoperative chemoradiation followed by surgery in adenocarcinomas of distal oesophagus, gastro-oesophageal junction and stomach. We retrospectively reviewed the institutional patient database. The therapeutic response was re-evaluated as a percentage of residual tumor cells in surgical resection specimens. Overall survival (OS) and disease-free survival (DFS) were assessed. The effect primary tumour location, clinical and pathological TNM stage, and histopathological factors (histological type, grade, angioinvasion, perineural invasion, tumour response) on treatment outcome were evaluated...
May 27, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28549783/irinotecan-temozolomide-with-temsirolimus-or-dinutuximab-in-children-with-refractory-or-relapsed-neuroblastoma-cog-anbl1221-an-open-label-randomised-phase-2-trial
#3
Rajen Mody, Arlene Naranjo, Collin Van Ryn, Alice L Yu, Wendy B London, Barry L Shulkin, Marguerite T Parisi, Sabah-E-Noor Servaes, Mitchell B Diccianni, Paul M Sondel, Julia G Bender, John M Maris, Julie R Park, Rochelle Bagatell
BACKGROUND: Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of irinotecan and temozolomide has activity in these patients, and its acceptable toxicity profile makes it an excellent backbone for study of new agents. We aimed to test the addition of temsirolimus or dinutuximab to irinotecan-temozolomide in patients with relapsed or refractory neuroblastoma. METHODS: For this open-label, randomised, phase 2 selection design trial of the Children's Oncology Group (COG; ANBL1221), patients had to have histological verification of neuroblastoma or ganglioneuroblastoma at diagnosis or have tumour cells in bone marrow with increased urinary catecholamine concentrations at diagnosis...
May 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28549148/risk-factors-for-invasive-fungal-disease-in-pediatric-cancer-and-hematopoietic-stem-cell-transplantation-a-systematic-review
#4
Brian T Fisher, Paula D Robinson, Thomas Lehrnbecher, William J Steinbach, Theoklis E Zaoutis, Bob Phillips, Lillian Sung
Background.: Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. Methods.: We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD...
May 26, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28549034/mantle-cell-lymphoma-with-hodgkin-and-reed-sternberg-cells-review-with-illustrative-case
#5
Steven Kramer, Guldeep Uppal, Zi-Xuan Wang, Jerald Z Gong
Non-Hodgkin lymphoma may occasionally contain large transformed cells resembling Hodgkin and Reed-Sternberg cells (HRS cells). We report a 63-year-old man with HRS cells in a recurrent mantle cell lymphoma (MCL). The patient initially presented with orbital MCL and recurred after 8 years with widespread involvement. The HRS cells were present in the recurrent disease but not in the initial orbital lesions, suggesting a transformed event after a prolonged disease course. Morphologically, the HRS cells were single cells and small clusters among the MCL cells and were frequently accompanied by histiocytes but without eosinophils or other inflammatory cells...
May 25, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28547859/giant-cell-tumor-of-the-mobile-spine-occurring-in-pregnancy-a-case-report-and-literature-review
#6
Kai Zheng, Ming Xu, Bing Wang, Xiu-Chun Yu, Yong-Cheng Hu
Giant cell tumor (GCT) is a benign, locally aggressive tumor that rarely occurs in the spine. They usually occur in patients between 20 and 40 years of age; some patients with GCT present in hospital with pregnancy. The management of these patients can be challenging. The current study reports a case of GCT located in the sixth thoracic vertebra of a 31-year-old female at 34 weeks of gestation. An osteolytic lesion, 3.5 cm × 3.5 cm in diameter, was identified on CT. An MRI test of the lesion revealed a soft tissue mass involving the T 6-7 vertebrae, extending to the right pedicle of the T 6 vertebra and causing significant spinal cord compression...
May 26, 2017: Orthopaedic Surgery
https://www.readbyqxmd.com/read/28547076/purinergic-signaling-during-intestinal-inflammation
#7
REVIEW
Maria Serena Longhi, Alan Moss, Zhenghui Gordon Jiang, Simon C Robson
Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer...
May 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28546901/macrophages-as-effectors-of-acute-and-chronic-allograft-injury
#8
Yianzhu Liu, Malgorzata Kloc, Xian C Li
Organ transplants give a second chance of life to patients with end-stage organ failure. However, the immuno-logical barriers prove to be very challenging to overcome and graft rejection remains a major hurdle to long-term transplant survival. For decades, adaptive immunity has been the focus of studies, primarily based on the belief that T cells are necessary and sufficient for rejection. With better-developed immunosuppressive drugs and protocols that effectively control adaptive cells, innate immune cells have emerged as key effector cells in triggering graft injury and have therefore attracted much recent attention...
December 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28546779/emerging-treatment-options-for-the-management-of-hodgkin-s-lymphoma-clinical-utility-of-nivolumab
#9
REVIEW
David A Bond, Lapo Alinari
Classical Hodgkin's lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28546563/microbiota-in-t-cell-homeostasis-and-inflammatory-diseases
#10
REVIEW
Naeun Lee, Wan-Uk Kim
The etiology of disease pathogenesis can be largely explained by genetic variations and several types of environmental factors. In genetically disease-susceptible individuals, subsequent environmental triggers may induce disease development. The human body is colonized by complex commensal microbes that have co-evolved with the host immune system. With the adaptation to modern lifestyles, its composition has changed depending on host genetics, changes in diet, overuse of antibiotics against infection and elimination of natural enemies through the strengthening of sanitation...
May 26, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28546500/myeloid-derived-suppressor-cells-a-new-therapeutic-target-to-overcome-resistance-to-cancer-immunotherapy
#11
REVIEW
Jason A Chesney, Robert A Mitchell, Kavitha Yaddanapudi
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate during pathologic conditions, such as cancer. Patients diagnosed with advanced metastatic cancers have an average survival of 12-24 mo, a survival time that hasn't changed significantly in the past 30 yr. Despite some encouraging improvements in response rates and overall survival in patients receiving immunotherapies, such as immune checkpoint inhibitors, most patients will ultimately progress...
May 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28546083/mechanisms-of-tolerance-and-potential-therapeutic-interventions-in-alopecia-areata
#12
REVIEW
Gabriel Skogberg, Sonya Jackson, Annika Åstrand
This review aims to address the mechanisms of compromised immune tolerance contributing to the development and maintenance of Alopecia Areata (AA). Our goal is to also highlight future treatment opportunities and therapeutics that will safely and efficiently restore hair growth and maintain patients in remission. AA is a presumptive autoimmune disorder that coincides and genetically clusters to several other autoimmune diseases. In this review, we pay attention to the learnings from the mechanistic research and drug development in these other autoimmune conditions...
May 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28545680/a-role-for-tropomyosins-in-activity-dependent-bulk-endocytosis
#13
REVIEW
R S Gormal, N Valmas, T Fath, F A Meunier
Bulk endocytosis allows stimulated neurons to take up a large portion of the presynaptic plasma membrane in order to regenerate synaptic vesicle pools. Actin, one of the most abundant proteins in eukaryotic cells, plays an important role in this process, but a detailed mechanistic understanding of the involvement of the cortical actin network is still lacking, in part due to the relatively small size of nerve terminals and the limitation of optical microscopy. We recently discovered that neurosecretory cells display a similar, albeit much larger, form of bulk endocytosis in response to secretagogue stimulation...
May 22, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28545567/cancer-immunotherapy-by-targeting-immune-checkpoints-mechanism-of-t-cell-dysfunction-in-cancer-immunity-and-new-therapeutic-targets
#14
REVIEW
Hwei-Fang Tsai, Ping-Ning Hsu
Immune checkpoints or coinhibitory receptors, such as cytotoxic T lymphocyte antigen (CTLA)-4 and programmed death (PD)-1, play important roles in regulating T cell responses, and they were proven to be effective targets in treating cancer. In chronic viral infections and cancer, T cells are chronically exposed to persistent antigen stimulation. This is often associated with deterioration of T cell function with constitutive activation of immune checkpoints, a state called 'exhaustion', which is commonly associated with inefficient control of tumors and persistent viral infections...
May 25, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28545479/endoplasmic-reticulum-stress-and-inflammation-in-the-central-nervous-system
#15
REVIEW
Neil T Sprenkle, Savannah G Sims, Cristina L Sánchez, Gordon P Meares
Persistent endoplasmic reticulum (ER) stress is thought to drive the pathology of many chronic disorders due to its potential to elicit aberrant inflammatory signaling and facilitate cell death. In neurodegenerative diseases, the accumulation of misfolded proteins and concomitant induction of ER stress in neurons contributes to neuronal dysfunction. In addition, ER stress responses induced in the surrounding neuroglia may promote disease progression by coordinating damaging inflammatory responses, which help fuel a neurotoxic milieu...
May 25, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28545251/oxidative-stress-promoter-of-allergic-sensitization-to-protease-allergens
#16
REVIEW
Leonie S van Rijt, Lara Utsch, René Lutter, Ronald van Ree
Allergies arise from aberrant T helper type 2 responses to allergens. Several respiratory allergens possess proteolytic activity, which has been recognized to act as an adjuvant for the development of a Th2 response. Allergen source-derived proteases can activate the protease-activated receptor-2, have specific effects on immune cells by cleaving cell membrane-bound regulatory molecules, and can disrupt tight junctions. The protease activity can induce a non-allergen-specific inflammatory response in the airways, which will set the stage for an allergen-specific Th2 response...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28543935/neurodegeneration-in-ataxia-telangiectasia-multiple-roles-of-atm-kinase-in-cellular-homeostasis
#17
REVIEW
Kay Rui Choy, Dianne J Watters
Ataxia-Telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (Ataxia-Telangiectasia Mutated) gene. ATM is a sensor of DNA Double Strand Breaks and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signalling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease...
May 22, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28543931/severe-asthma-in-children
#18
REVIEW
Andrew Bush, Louise Fleming, Sejal Saglani
Most children with asthma have their disease easily controlled if low-dose inhaled corticosteroids (ICSs) are regularly and correctly administered. If a child presents with asthma which is apparently resistant to therapy with high-dose ICS and other controllers, then they have problematic severe asthma. However, in light of the UK National Review of Asthma Deaths, definitions of severe asthma based solely on the levels of prescribed treatment are too narrow. A detailed assessment of all such children should be performed...
May 25, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28543699/immune-and-molecular-correlates-in-melanoma-treated-with-immune-checkpoint-blockade
#19
REVIEW
Elizabeth H Byrne, David E Fisher
Immunotherapy for metastatic melanoma has a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable and sometimes complete remission of metastatic melanoma is now achievable in some patients who receive checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic melanoma, focusing on tumor programmed death ligand 1 expression, major histocompatibility complex class I expression, mutational load in the tumor, and T-cell infiltration into the tumor...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543698/adoptive-t-cell-therapy-an-overview-of-obstacles-and-opportunities
#20
REVIEW
Erez Nissim Baruch, Amy Lauren Berg, Michal Judith Besser, Jacob Schachter, Gal Markel
The therapeutic potential of adoptive cell therapy (ACT) in cancer patients was first acknowledged 3 decades ago, but it was an esoteric approach at the time. In recent years, technological advancements have transformed ACT into a viable therapeutic option that can be curative in some patients. In fact, current ACT response rates are 80% to 90% for hematological malignancies and 30% for metastatic melanoma refractory to multiple lines of therapy. Although these results are encouraging, there is still much to be done to fulfill ACT's potential, specifically with regard to improving clinical efficacy, expanding clinical indications, reducing toxicity, and increasing production and cost-effectiveness...
June 1, 2017: Cancer
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