11,389 results match your criteria rare target

EML4-ALK fusion variant.3 and co-occurrent PIK3CA E542K mutation exhibiting primary resistance to three generations of ALK inhibitors.

Cancer Genet 2021 May 28;256-257:131-135. Epub 2021 May 28.

Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.

The ALK inhibitors are promising therapeutic agents against lung cancer harboring ALK fusion genes and are currently under development up to the third generation. However, its therapeutic effects are reported to be affected by differences in ALK variants and co-occurrent mutations. Materials and Methods; We experienced an autopsy case of an ALK-positive lung cancer patient who showed primary resistance to three generations of ALK inhibitors. Read More

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Dismantling the bacterial glycocalyx: Chemical tools to probe, perturb, and image bacterial glycans.

Bioorg Med Chem 2021 Jun 7;42:116268. Epub 2021 Jun 7.

Department of Chemistry & Biochemistry, Bowdoin College, 6600 College Station, Brunswick, ME 04011, USA. Electronic address:

The bacterial glycocalyx is a quintessential drug target comprised of structurally distinct glycans. Bacterial glycans bear unusual monosaccharide building blocks whose proper construction is critical for bacterial fitness, survival, and colonization in the human host. Despite their appeal as therapeutic targets, bacterial glycans are difficult to study due to the presence of rare bacterial monosaccharides that are linked and modified in atypical manners. Read More

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Chemical constituents from Tinospora sagittata and their biological activities.

Fitoterapia 2021 Jun 12:104963. Epub 2021 Jun 12.

School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address:

Six undescribed low-polarity compounds including three rare 14-methylergostane steroids (1-3), one euphane triterpenoid (4) and two octadecanoic acid ethyl esters (5 and 6), along with ten previously reported terpenyl cometabolites (7-16), were isolated from the stems of Tinospora sagittata. Their structures were determined by detailed spectroscopic analyses and comparison with structurally related known compounds, and all of them have been reported from T. sagittata for the first time. Read More

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25 years of biologicals in IBD: What´s all the hype about?

J Intern Med 2021 Jun 15. Epub 2021 Jun 15.

University Hospital Tübingen, Tübingen, Germany.

25 years ago the field was revolutionized by the introduction of infliximab as the first hybrid anti-TNF-antibody. Subsequently, other humanized anti-TNFs were developed and marketed, followed by antibodies to new targets including integrins (vedolizumab) and interleukin (IL) 12/23 (ustekinumab). All these so-called biologicals were shown in registrational trials to induce remission superior to placebo but consistently were effective in only a minority of patients. Read More

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Sleep and physical activity patterns in adults and children with Bardet-Biedl syndrome.

Orphanet J Rare Dis 2021 Jun 14;16(1):276. Epub 2021 Jun 14.

Department of Pediatrics, Marshfield Clinic Health System, Marshfield, WI, USA.

Background: Overweight and obesity are common features of the rare disease Bardet-Biedl syndrome (BBS). Sleep and physical activity are behaviors that might impact overweight and obesity and thus may play a key role in the health and well-being of people with BBS. Objectively-measured sleep and physical activity patterns in people with BBS are not well known. Read More

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Sequential everolimus for angiomyolipoma associated with tuberous sclerosis complex: a prospective cohort study.

Orphanet J Rare Dis 2021 Jun 14;16(1):277. Epub 2021 Jun 14.

Department of Urology, the Third Medical Centre, Chinese PLA General Hospital, 69 Yong Ding Road, Beijing, 100039, China.

Background: To evaluate the efficacy, safety and health economics of sequential everolimus in treating angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC).

Methods: In this prospective cohort study, patients met the inclusion criteria received standard or sequential treatment according to their willingness. All patients received an initial dose of everolimus (10 mg oral, once a day) for 3 months. Read More

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Metabolic inhibitors of bacterial glycan biosynthesis.

Chem Sci 2020 Jan 8;11(7):1761-1774. Epub 2020 Jan 8.

Department of Chemistry & Biochemistry, Bowdoin College 6600 College Station Brunswick ME 04011 USA

The bacterial cell wall is a quintessential drug target due to its critical role in colonization of the host, pathogen survival, and immune evasion. The dense cell wall glycocalyx contains distinctive monosaccharides that are absent from human cells, and proper assembly of monosaccharides into higher-order glycans is critical for bacterial fitness and pathogenesis. However, the systematic study and inhibition of bacterial glycosylation enzymes remains challenging. Read More

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January 2020

Synchronous adenocarcinoma and marginal zone B-cell lymphoma of the colon. A case report.

Int J Surg Case Rep 2021 May 28;84:106025. Epub 2021 May 28.

Departement of pathology, Central Hospital of The Army, Dr Mohamed Seghir Nekkache, Ain Naâdja BP 244, 16205 Kouba, Algiers, Algeria.

Introduction And Importance: The association of colonic adenocarcinoma with lymphoma is a rare entity. The purpose of our presentation is to draw the attention of the endoscopist, and the surgeon, to the need to remove any suspicious lesions in the exploration for colorectal cancer. The pathologist should be warned about this association in the face of any unusual change in the lymphatic environment around an adenocarcinoma. Read More

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Chemical synthesis of the rare D-Fuc3NAc containing tetrasaccharide repeating unit of the O-antigenic polysaccharide from E. coli O74.

Carbohydr Res 2021 Jun 7;506:108366. Epub 2021 Jun 7.

Sweet Lab, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia 741246, India. Electronic address:

Chemical synthesis of the tetrasaccharide repeating unit of the O-antigen from E. coli O74 is accomplished by a convergent [2 + 2] block synthesis strategy. The challenging rare D-Fuc3NAc has been prepared using DTBP and TIPST mediated deoxygenation reaction. Read More

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Construction of a Super-Folder Fluorescent Protein-Guided Secretory Expression System for the Production of Phospholipase D in .

J Agric Food Chem 2021 Jun 14. Epub 2021 Jun 14.

College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.

Phospholipids (PLs) are one of the main ingredients in food and nutraceutical, cosmetics, agriculture, and pharmaceutical products. Phospholipase D (PLD) is a crucial enzyme for the biocatalytic synthesis or modification of PLs. Here, to prepare PLD more efficiently, we constructed a PLD expression and secretion system in and developed an environmentally friendly reaction system. Read More

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Management of Hematologic Adverse Events Associated With Immune Checkpoint Inhibitors.

J Adv Pract Oncol 2021 May 1;12(4):392-404. Epub 2021 May 1.

Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Immune checkpoint inhibitors target suppressor receptors, including cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1). The activated T cells are not antigen specific; therefore, the blockade of the immune checkpoint may result in the development of autoimmune adverse events. The most common immune-related adverse events (irAEs) are rash, colitis, and endocrinopathies. Read More

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Use of a -P building block - a way to networks of host-guest assemblies.

Chem Sci 2020 Aug 12;11(34):9067-9071. Epub 2020 Aug 12.

Institute of Inorganic Chemistry, University of Regensburg 93040 Regensburg Germany

Despite the proven ability to form supramolecular assemblies coordination to copper halides, organometallic building blocks based on four-membered -P ligands find only very rare application in supramolecular chemistry. To date, only three types of supramolecular aggregates were obtained based on the polyphosphorus end-deck complexes CpTa(CO)(η-P) (: Cp = Cp''; : Cp = Cp'''), with none of them, however, possessing a guest-accessible void. To achieve this target, the use of silver salts of the weakly coordinating anion SbF was investigated as to their self-assembly in the absence and in the presence of the template molecule PSe. Read More

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Reversibility of motor dysfunction in the rat model of NGLY1 deficiency.

Mol Brain 2021 Jun 13;14(1):91. Epub 2021 Jun 13.

Glycometabolic Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.

N-glycanase 1 (NGLY1) deficiency is a rare inherited disorder characterized by developmental delay, hypolacrima or alacrima, seizure, intellectual disability, motor deficits, and other neurological symptoms. The underlying mechanisms of the NGLY1 phenotype are poorly understood, and no effective therapy is currently available. Similar to human patients, the rat model of NGLY1 deficiency, Ngly1-/-, shows developmental delay, movement disorder, somatosensory impairment, scoliosis, and learning disability. Read More

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High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma.

Transl Oncol 2021 Jun 9;14(8):101146. Epub 2021 Jun 9.

Department of Otolaryngology Head & Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai 200011, China; Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address:

Head and neck paragangliomas (HNPGLs) are rare neoplasms that represent difficult treatment paradigms in neurotology. Germline mutations in genes encoding succinate dehydrogenase (SDH) are the cause of nearly all familial HNPGLs. However, the molecular mechanisms underlying tumorigenesis remain unclear. Read More

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Drug target gene-based analyses of drug repositionability in rare and intractable diseases.

Sci Rep 2021 Jun 11;11(1):12338. Epub 2021 Jun 11.

Laboratory of Rare Disease Resource Library, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, Japan.

Drug development for rare and intractable diseases has been challenging for decades due to the low prevalence and insufficient information on these diseases. Drug repositioning is increasingly being used as a promising option in drug development. We aimed to analyze the trend of drug repositioning and inter-disease drug repositionability among rare and intractable diseases. Read More

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Single-cell lineage tracing of metastatic cancer reveals selection of hybrid EMT states.

Cancer Cell 2021 May 28. Epub 2021 May 28.

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell & Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

The underpinnings of cancer metastasis remain poorly understood, in part due to a lack of tools for probing their emergence at high resolution. Here we present macsGESTALT, an inducible CRISPR-Cas9-based lineage recorder with highly efficient single-cell capture of both transcriptional and phylogenetic information. Applying macsGESTALT to a mouse model of metastatic pancreatic cancer, we recover ∼380,000 CRISPR target sites and reconstruct dissemination of ∼28,000 single cells across multiple metastatic sites. Read More

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Pluripotent Stem Cells: Cancer Study, Therapy, and Vaccination.

Stem Cell Rev Rep 2021 Jun 11. Epub 2021 Jun 11.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Introduction: Pluripotent stem cells (PSCs) are promising tools for modern regenerative medicine applications because of their stemness properties, which include unlimited self-renewal and the ability to differentiate into all cell types in the body. Evidence suggests that a rare population of cells within a tumor, termed cancer stem cells (CSCs), exhibit stemness and phenotypic plasticity properties that are primarily responsible for resistance to chemotherapy, radiotherapy, metastasis, cancer development, and tumor relapse. Different therapeutic approaches that target CSCs have been developed for tumor eradication. Read More

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Complicated embolisation of late endoleak via direct sac puncture: not all endoleaks are a type II endoleak.

CVIR Endovasc 2021 Jun 11;4(1):50. Epub 2021 Jun 11.

Department of Vascular Surgery, John Hunter Hospital, Newcastle, NSW, 2305, Australia.

Background: Endoleaks after endovascular aortic aneurysm repair (EVAR) occur frequently with type 2 being the most common. Treatment of type 2 endoleaks is indicated if the aneurysmal sac increases in size.

Case Report: In this case report, we will discuss a patient who presented with aneurysmal sac size increase 11 years after undergoing EVAR for an asymptomatic abdominal aortic aneurysm which extended into the iliac arteries. Read More

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Identifying Patterns of Failure and Risk Factors for Recurrence in Patients of Paratesticular Sarcomas: Protocol of a Systematic Review and Meta-Analysis.

Int J Surg Protoc 2021 May 28;25(1):84-91. Epub 2021 May 28.

Department of Radiotherapy, All India Institute of Medical Sciences, New Delhi, IN.

Introduction: Para testicular sarcomas are rare mesenchymal tumors that affect patients of all ages. Unlike other sites of sarcoma, they tend to be of lower grade and have a higher propensity for lymphatic spread. Management is hampered by the small number of patients who differ in terms of tumor grade and histology. Read More

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Transcriptome Profile Analysis of Reveals the Drought Stress-Induced Long Non-coding RNAs Associated With Photosynthesis, Chlorophyll Synthesis, Fatty Acid Synthesis and Degradation.

Front Plant Sci 2021 25;12:643182. Epub 2021 May 25.

Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

Long non-coding RNAs (lncRNAs) play an important role in the response of plants to drought stress. The previous studies have reported that overexpression of and could enhance drought tolerance and improve the oil content in and , and most of the efforts have been invested in the gene function analysis, there is little understanding of how genes that involved in these important pathways are regulated. In the present study, the transcriptomic results of and over-expressed (OE) lines were compared with the RNAi lines, mutant lines and control lines under long-term and short-term drought treatment, a series of differentially expressed lncRNAs were identified, and their regulation patterns in mRNA were also investigated in above mentioned materials. Read More

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Therapies in preclinical and clinical development for Angelman syndrome.

Expert Opin Investig Drugs 2021 Jun 10. Epub 2021 Jun 10.

MDUK Oxford Neuromuscular Center, Oxford, UK.

Introduction: Angelman syndrome is a rare genetic neurodevelopmental disorder, caused by deficiency or abnormal function of the maternal ubiquitin protein-ligase E3A, known as UBE3A, in the central nervous system. Currently, there is no disease-modifying treatment available, but the therapeutic pipeline of Angelman syndrome includes at least 15 mechanistically different approaches at preclinical or clinical development. In the coming years, several clinical trials will be enrolling patients and, therefore, Angelman syndrome community needs to be aware of all options. Read More

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Plasmacytoid urothelial carcinoma: response to chemotherapy and oncologic outcomes.

Bladder Cancer 2020 28;6(1):71-81. Epub 2020 Mar 28.

Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.

Background: Plasmacytoid urothelial carcinoma is a rare bladder cancer variant with scarce data on outcomes and prognostic factors.

Objective: We report our institutional experience with this histology to determine response to neoadjuvant chemotherapy, definitive surgery and survival.

Methods: We conducted a retrospective chart review of consecutive patients with plasmacytoid, as well as conventional urothelial carcinoma (for comparison) seen in our institution (2007 - 2018). Read More

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Human amyotrophic lateral sclerosis excitability phenotype screen: Target discovery and validation.

Cell Rep 2021 Jun;35(10):109224

F.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address:

Drug development is hampered by poor target selection. Phenotypic screens using neurons differentiated from patient stem cells offer the possibility to validate known and discover novel disease targets in an unbiased fashion. To identify targets for managing hyperexcitability, a pathological feature of amyotrophic lateral sclerosis (ALS), we design a multi-step screening funnel using patient-derived motor neurons. Read More

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JAK2 Rearrangements Are a Recurrent Alteration in CD30+ Systemic T-Cell Lymphomas With Anaplastic Morphology.

Am J Surg Pathol 2021 Jul;45(7):895-904

Department of Pathology, Massachusetts General Hospital, Harvard Medical School.

Peripheral T-cell lymphoma (PTCL) comprises a heterogenous group of rare mature T-cell neoplasms. While some PTCL subtypes are well-characterized by histology, immunophenotype, and recurrent molecular alterations, others remain incompletely defined. In particular, the distinction between CD30+ PTCL, not otherwise specified and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma can be subject to disagreement. Read More

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Treatment of lymphocyte-variant hypereosinophilic syndrome (L-HES): what to consider after confirming the elusive diagnosis.

Br J Haematol 2021 Jun 8. Epub 2021 Jun 8.

Division of Hematology, University of British Columbia, Vancouver, BC, Canada.

Lymphocyte-variant hypereosinophilic syndrome (L-HES) is a rare disease driven by immunophenotypically aberrant T cells producing eosinophilopoetic cytokines such as interleukin-5 (IL-5). Treatment is challenging because L-HES is relatively steroid resistant and not amenable to tyrosine kinase inhibitors. We searched the literature for clinical trials and observational studies, including case reports, of patients treated for L-HES. Read More

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Sirolimus in the treatment of kaposiform lymphangiomatosis.

Orphanet J Rare Dis 2021 Jun 8;16(1):260. Epub 2021 Jun 8.

Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, #37# Guo-Xue-Xiang, Chengdu, 610041, China.

Background: Kaposiform lymphangiomatosis (KLA), which is a new subtype of generalized lymphatic anomaly, is a rare disease with a poor prognosis. Currently, there is no standard treatment due to the poor understanding of KLA. Sirolimus, which is an inhibitor of mammalian target of rapamycin, has been shown to have promising potential in the treatment of complicated vascular anomalies. Read More

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Demographics, in-hospital analysis, and prevalence of 33 rare diseases with effective treatment in Shanghai.

Orphanet J Rare Dis 2021 Jun 8;16(1):262. Epub 2021 Jun 8.

Center for Biomedical Informatics, Shanghai Children's Hospital, Shanghai, China.

Background: Rare diseases are ailments which impose a heavy burden on individual patients and global society as a whole. The rare disease management landscape is not a smooth one-a rare disease is quite often hard to diagnose, treat, and investigate. In China, the country's rapid economic rise and development has brought an increased focus on rare diseases. Read More

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Botulinum toxin treatment of dystonic anterocollis: What to inject.

Parkinsonism Relat Disord 2021 May 29;88:34-39. Epub 2021 May 29.

ENT Department, St George's Hospital NHS Foundation Trust, London, United Kingdom.

Background: Anterocollis (AC) is a rare form of cervical dystonia, which responds poorly to botulinum toxin treatment.

Objectives: To recognise the different clinical phenotypes of AC and to detail the selection of muscles from the results of treating a cohort of 15 AC patients with Botulinum Toxin.

Methods: The study was performed using prospectively collected data. Read More

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Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia.

J Med Chem 2021 Jun 8. Epub 2021 Jun 8.

Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada.

Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Read More

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Ginsenoside Rg4 enhances the inductive effects of human dermal papilla spheres on hair growth via the AKT/GSK-3β/β-catenin signaling pathway.

J Microbiol Biotechnol 2021 May 31. Epub 2021 May 31.

Research Institute for Molecular-Targeted Drugs, Department of Cosmetics Engineering, Konkuk University, Seoul 05029, Republic of Korea.

Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities, including antioxidant and anti-inflammatory properties, in several cell types. The purpose of this study was to use an model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture, and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 µg/mL) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Read More

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