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1.
Biochem Biophys Res Commun ; 710: 149881, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38583233

ABSTRACT

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent.


Subject(s)
Antineoplastic Agents , Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck , N-Acetylneuraminic Acid/metabolism , Maackia/chemistry , Maackia/metabolism , Mouth Neoplasms/pathology , Chromatography, Liquid , Ligands , Tandem Mass Spectrometry , Lectins/pharmacology , Antineoplastic Agents/pharmacology , Sequence Analysis , Cell Movement
2.
Cureus ; 13(4): e14576, 2021 Apr 20.
Article in English | MEDLINE | ID: mdl-34035998

ABSTRACT

Pemphigus is a broad term that is used to describe a group of bullous autoimmune diseases affecting the skin and mucous membranes; the pathogenesis involves autoantibodies directed against various cell junction desmosomal proteins. In patients with a history of malignancy who present with bullous lesions, the differential diagnosis may include, but is not limited to, paraneoplastic pemphigus (PNP) and pemphigus vulgaris (PV) secondary to a primary autoimmune process, or induced by chemotherapy or radiation therapy. In this report, we present a case of refractory PV in a patient with stable esophageal cancer, five years after undergoing radiation therapy. He was poorly responsive to corticosteroids and intravenous immunoglobulin (IVIG). PNP or PV in a patient with stable esophageal malignancy has not been previously reported. PNP and PV can have overlapping autoantigens [desmoglein types 1 and 3 (DSG1 and DSG3)] as well as similar presentations. Thus, distinguishing between the two may be challenging in a patient with a history of cancer. More research must be done to determine if PNP can be seen in a patient with stable esophageal malignancy and, similarly, if PV can be precipitated by stable esophageal malignancy. Such research would aid in determining whether or not similar presentations are more severe or refractory to standard treatment regimens, thereby contributing to improve treatment strategies.

3.
Cureus ; 13(1): e12996, 2021 Jan 29.
Article in English | MEDLINE | ID: mdl-33659130

ABSTRACT

Symptoms of dry eyes or dry mouth, otherwise known as sicca symptoms, are not always present in patients with Sjögren's syndrome (SS). Approximately 20% of patients with SS do not have sicca symptoms. An unusual case of a patient presenting with complete left-sided facial hemiparesis, a history of partial bilateral sensorineural hearing loss who was found to have elevated antinuclear antibody (ANA) with high titer positive SSA/Ro antibody, evidence of bilateral parotitis on imaging and absence of sicca symptoms, prompted us to perform a literature review. Twelve case reports relating facial nerve palsy and Sjögren's were found and only one described a similar constellation of features of unilateral facial weakness and otalgia. Management of facial nerve palsy related to Sjögren's is unclear but pharmacological agents have included corticosteroids, intravenous immune globulin (IVIG), cyclophosphamide, and plasmapheresis. This case report describes a patient whose facial nerve palsy is attributed to SS, explores peripheral and central nervous system involvement in SS, and provides some recommended treatments.

4.
Cureus ; 12(11): e11750, 2020 Nov 28.
Article in English | MEDLINE | ID: mdl-33403180

ABSTRACT

We describe a 46-year-old male with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who presented as a Kawasaki-like syndrome with features including prolonged fever, bilateral conjunctivitis, oral mucosal swelling, diffuse erythematous rash, cervical and hilar lymphadenopathy, as well as cardiovascular complications and multi-organ failure. There are several reports of a similar clinical entity mimicking Kawasaki disease (KD) in the pediatric population, which has been termed Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) by the Royal College of Pediatric and Child Health. To our knowledge, to date, there has been only one case report of COVID-19 presenting as KD in an adult patient.

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