Introduction: The neck imaging reporting and data system (NIRADS) lexicon is aimed at surveillance of head and neck cancer during post-treatment follow-up using either a CECT or PET-CT scan. These recommendations standardize management, reduce interobserver variability, and standardizes scientific communication.
Objectives: The primary aim of this study was to validate the correlation between the NI-RADS category and disease status on clinical follow-up and histopathological analysis.
Background: Over the last three years, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a global impact. COVID-19 has led to diagnostic and treatment delays in head and neck squamous cell cancers (HNSCCs). Both cancer and COVID-19 trigger systemic inflammatory responses that can result in cytokine storms, creating a favorable tumor microenvironment that supports tumor growth.
View Article and Find Full Text PDFObjective: The aim of the study was to investigate whether the IRAK1/JAK2/Flt3 inhibitor pacritinib prevents disease development in the lupus-prone ABIN1[D485N] knock-in mouse.
Methods: ABIN1[D485N] knock-in mice aged 8 weeks were fed for 10 weeks on a diet containing pacritinib. Body weight was monitored, and serum collected at the end to measure pacritinib, autoantibody and immunoglobulin levels.
Background: The data regarding the use of neoadjuvant chemotherapy in technically unresectable head and neck cancer (HNC) is limited and real-world studies are needed to look for the efficacy and toxicities of this approach.
Patients And Methods: This is a retrospective study conducted in the Medical Oncology department of our hospital. All technically unresectable HNC patients who underwent neoadjuvant chemotherapy between May 2018 and May 2020 were included in this analysis.
Indian J Otolaryngol Head Neck Surg
December 2022
Indian J Otolaryngol Head Neck Surg
October 2022
Verrucous carcinoma (VC) is a locally invasive uncommon histopathological variant of oral squamous cell cancer. There is paucity of literature regarding control rates in these cases. We intend to report the outcomes in terms of administered treatment and control rates.
View Article and Find Full Text PDFIn this review, we have summarized classical post-translational modifications (PTMs) such as phosphorylation, ubiquitylation, and SUMOylation of the different components of one of the most studied NLRP3, and other emerging inflammasomes. We will highlight how the discovery of these modifications have provided mechanistic insight into the biology, function, and regulation of these multiprotein complexes not only in the context of the innate immune system but also in adaptive immunity, hematopoiesis, bone marrow transplantation, as well and their role in human diseases. We have also collected available information concerning less-studied modifications such as acetylation, ADP-ribosylation, nitrosylation, prenylation, citrullination, and emphasized their relevance in the regulation of inflammasome complex formation.
View Article and Find Full Text PDFHOIL-1, a component of the linear ubiquitin chain assembly complex (LUBAC), ubiquitylates serine and threonine residues in proteins by esterification. Here, we report that mice expressing an E3 ligase-inactive HOIL-1[C458S] mutant accumulate polyglucosan in brain, heart and other organs, indicating that HOIL-1's E3 ligase activity is essential to prevent these toxic polysaccharide deposits from accumulating. We found that HOIL-1 monoubiquitylates glycogen and α1:4-linked maltoheptaose in vitro and identify the C6 hydroxyl moiety of glucose as the site of ester-linked ubiquitylation.
View Article and Find Full Text PDFThe expression of TNF-Receptor Associated Factor 6 (TRAF6) is essential for many physiological processes. Here we studied the phenotype of TRAF6[L74H] knock-in mice which are devoid of TRAF6 E3 ligase activity in every cell of the body, but express normal levels of the TRAF6 protein. Remarkably, TRAF6[L74H] mice have none of the phenotypes seen in TRAF6 KO mice.
View Article and Find Full Text PDFObjective: We have reported previously that the IRAK4 inhibitor PF06426779 given to ubiquitin-binding-defective ABIN1[D485N] mice at 6 weeks of age prevents the major facets of lupus that develop 10 weeks later. The present study was undertaken to investigate whether PF06426779 could reverse the lupus phenotype when administered to 13-week-old ABIN1[D485N] mice that had already developed symptoms of lupus.
Methods: Splenomegaly, the number of splenic neutrophils, T and Germinal Centre B (GCB) cells, serum levels of immunoglobulins, the extent of kidney, liver and lung pathology, and glomerular IgA and IgM were measured after feeding 13-week-old ABIN1[D485N] and wild-type mice for another 10 weeks with R&M3 diet with and without PF06426779 (4 g/kg).
The atypical E3 ligase HOIL-1 forms ester bonds between ubiquitin and serine/threonine residues in proteins, but the physiological roles of this unusual modification are unknown. We now report that IL-18 signalling leading to the production of interferon γ (IFNγ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is enhanced in cytotoxic T cells from knock-in mice expressing the E3 ligase-inactive HOIL-1[C458S] mutant, demonstrating that the formation of HOIL-1-catalysed ester-linked ubiquitin bonds restricts the activation of this pathway. We show that the interaction of IRAK2 with TRAF6 is required for IL-18-stimulated IFN-γ and GM-CSF production, and that the increased production of these cytokines in cytotoxic T cells from HOIL-1[C458S] mice correlates with an increase in both the number and size of the Lys63/Met1-linked hybrid ubiquitin chains attached to IRAK2 in these cells.
View Article and Find Full Text PDFIntroduction: Concurrent chemoradiotherapy (CTRT) remains one of the treatment options in patients with muscle invasive bladder cancer (MIBC) unwilling/unsuitable for radical surgery. We evaluated the role of volumetric modulated arc therapy (VMAT) in MIBC patients treated with definitive CTRT.
Material And Methods: 25 patients of histologically proven transitional cell MIBC (T2-T4a, N0, M0) unwilling/unsuitable for radical surgery (after maximal transurethral resection of bladder tumour) were recruited in this prospective study.
Purpose: Adjuvant radiotherapy (RT) in buccal mucosa cancers is guided by histopathological factors. The decision to treat ipsilateral or bilateral draining lymph node is on physician discretion and guidelines do not have a defined indication regarding this. We aimed to analyze the failure patterns and survival in buccal mucosa cancers treated with adjuvant ipsilateral RT.
View Article and Find Full Text PDFBackground: The standard of care in high grade glioma (HGG) is maximal safe surgical resection followed by adjuvant radiotherapy (RT) with/without chemotherapy. For anaplastic gliomas, studies have shown use of procarbazine, lomustine, vincristine (PCV) improves overall survival (OS) and progression free survival (PFS). Currently, there is substantial evidence that molecular markers strongly predict prognosis and response to treatment.
View Article and Find Full Text PDFJAMA Otolaryngol Head Neck Surg
May 2020
We report that TLR7, IL-6, and the adaptive immune system are essential for autoimmunity and glomerulonephritis but not for liver pathology in mice expressing the ubiquitin-binding-defective ABIN1[D485N] mutant. The blood and organs of ABIN1[D485N] mice have exceptionally high numbers of patrolling monocytes (pMo), which develop independently of IL-6 and the adaptive immune system. They are detectable in the blood months before autoimmunity and organ pathology are seen and may have diagnostic potential.
View Article and Find Full Text PDFComponents of bacteria and viruses activate Toll-Like Receptors in host cells, triggering the formation of the Myddosome and a signalling network that culminates in the production and release of the inflammatory mediators required to combat pathogenic infection. The Myddosome initiates signalling by recruiting and activating five E3 ligases that generate hybrid ubiquitin chains and attach them to components of the Myddosome. These ubiquitin chains act as a scaffold for the recruitment and activation of ubiquitin-binding proteins, which include the "master" protein kinases TAK1 and IKKβ that drive inflammatory mediator production, as well as other proteins like ABIN1 and A20 that restrict activation of the network to prevent the overproduction of these substances that can lead to autoimmunity and organ damage.
View Article and Find Full Text PDFThe A20-binding inhibitor of NF-κB 2 (ABIN2) interacts with Met1-linked ubiquitin chains and is an integral component of the tumor progression locus 2 (Tpl2) kinase complex. We generated a knock-in mouse expressing the ubiquitin-binding-defective mutant ABIN2[D310N]. The expression of Tpl2 and its activation by TLR agonists in macrophages or by IL-1β in fibroblasts from these mice was unimpaired, indicating that the interaction of ABIN2 with ubiquitin oligomers is not required for the stability or activation of Tpl2.
View Article and Find Full Text PDFPurpose: We evaluated the correlation of the x-ray repair cross complementing gene 1 (XRCC1) Arg194Trp polymorphism with clinical outcomes in head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation therapy (CCRT).
Methods And Materials: In this prospective cohort study, we included 101 patients with HNSCC (oral cavity, pharynx, and larynx) who were aged ≥ 18 years, had stage III to IVB disease, had a Karnofsky Performance Status ≥ 80, and were deemed fit for CCRT. DNA extraction was done through polymerase chain reaction, and the genotypes of XRCC1 polymorphism were detected using designed restriction fragment length polymorphism.
Study Objective: The authors present the first ever laparoscopic-assisted uterus retrieval in a live donor for uterus transplant.
Design: A step-by-step surgical demonstration.
Setting: Galaxy CARE Laparoscopy Institute, Pune, India.
Objectives: We compared the prostate motion variability and toxicities between patients treated with gold marker registration based IG-IMRT (IG-IMRT-M) and bony landmark registration based IG-IMRT (IG-IMRT-B).
Methods: T1c-T3b (node negative), intermediate and high risk (non-metastatic) adenocarcinoma of prostate, age ≥18years, Karnofsky Performance Status of ≥70 were included in this retrospective study. The prostate motion variability, acute and late radiation toxicities between the two treatment arms (IG-IMRT-M versus IG-IMRT-B) were compared.
Purpose: Benzydamine is recommended for prophylaxis of oral mucositis (OM) in head and neck cancer (HNC) patients for radiation doses (<50 Gy). This study evaluates role of benzydamine for higher radiation doses (>50 Gy) with or without chemotherapy.
Methods: One hundred twenty patients of HNC with planned radiation doses of ≥60 Gy were randomized to group A (control radiotherapy alone), group B (study radiotherapy alone), group C (control chemoradiotherapy), or to group D (study chemoradiotherapy).
Polymorphisms in the TNIP1 gene encoding A20-binding inhibitor of NF-κB1 (ABIN1) predispose to lupus and other autoimmune diseases in at least eight human populations. We found previously that knock-in mice expressing a ubiquitin-binding-defective mutant of ABIN1 (ABIN1[D485N]) develop autoimmunity as they age and succumb to a disease resembling lupus nephritis in humans. In this article, we report that Flt3-derived dendritic cells from these mice overproduced type 1 IFNs upon stimulation with ligands that activate TLR7 or TLR9.
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