Erythema multiforme (EM) is an acute mucocutaneous hypersensitivity reaction characterized by skin eruptions with or without oral or other mucous membrane lesions. The main two variants are erythema minor and erythema major. Oral disease with typical EM lesions has been suggested as a third variant of EM. Known as oral EM, it is reported less and has no target lesions unlike the other two types, in its primary presentation. Objective: To report a manifestation of a rare case of oral EM and discuss various forms of EM including its management. Case report: A 22-year-old male patient reported with a complaint of oral and lip ulcers and severe pain for the past 7 days. The patient reported spontaneous onset of the lesions in the form of vesicles after consuming unknown artificially colored food items. The vesicles ruptured within two days leaving ulcers on the lips and the intraoral mucosa, with blood encrustations. The patient was unable to take food, was admitted for hydration, and was kept on corticosteroids. It took around three weeks for the patient to completely recover. Conclusion: The positive history of artificially colored food intake followed by the sudden onset of lesions and eruptions on the lips and oral mucosa led us to the diagnosis of oral EM. Early recognition and timely intervention benefits patients because the lesions associated with EM and related disorders can compromise life.

Langerhans cell histiocytosis (LCH) is an uncommon hematological disorder affecting infants and young children. LCH is a rare disorder of the reticuloendothelial system associated with proliferation of Langerhans cells and mature eosinophils. LCH can involve any bone, but the most common are pelvis, ribs, skull, long bones, vertebra, and facial bones. In the skull, frontal and parietal bones are commonly involved followed by the jaws, where mandible is more commonly affected than the maxilla. In this article, we report a case of LCH in a 5-year-old child involving the mandible. Swelling of one side of the face and aggressive periosteal reaction led to the diagnosis of monostotic LCH. The manuscript also summarizes the results of a literature search in PubMed of reported cases of LCH over the past 10 years.

No abstract

BackgroundGiven the pleiotropic functions of transforming growth factor-beta (TGFβ), current approaches to targeting systemic TGFβ will likely lead to suboptimal clinical activity and/or undesirable effects. Epidermal growth factor receptor (EGFR) is one of the most extensively validated tumor-associated antigens. Bicara Therapeutics has developed a novel bifunctional fusion protein, composed of a monoclonal antibody against EGFR and an extracellular domain of human TGFβ receptor II (TGFβRII). We demonstrate BCA101 has the potential to improve anti-tumor response by leveraging the cooperativity between EGFR and TGFβ signaling pathways while restricting TGFβ neutralization to EGFR-expressing tissues.MethodsFunctional neutralization of TGFβ by BCA101 was demonstrated by several in vitro assays which assessed TGFβ-dependent epithelial to mesenchymal transition (EMT), cell invasion, inducible Treg differentiation, as well as allogeneic immune responses in tumor cell/immune cell coculture assays. In vivo, the anti-tumor efficacy of BCA101 was determined in tumor xenograft mouse models, using either human tumor cell lines or patient-derived tumor cells (PDX), as well as in a humanized mouse model.ResultsIn vitro, we showed BCA101 is capable of simultaneously binding EGFR and TGFβ1 with a significantly higher affinity for EGFR. The incorporation of the TGFβRII ”trap” did not sterically interfere with the ability of BCA101 to bind EGFR, inhibit cell proliferation or mediate antibody-dependent cellular cytotoxicity (ADCC). Relative to cetuximab, BCA101 showed improved ability to reverse EMT and preserve ADCC activity. In tumor cell/immune cell co-culture assays, BCA101 increased production of proinflammatory cytokines associated with T and NK cell activation and suppressed VEGF release. Further, BCA101 inhibited differentiation of inducible Treg and displayed an immuno-potentiating profile in the BioMAP® TME model. In vivo, biodistribution studies showed that BCA101 localized to tumor tissues in xenograft mouse models, with comparable kinetics as cetuximab. TGFβ in tissues was neutralized to about 90% at 10 mg/kg of BCA101 while equimolar doses of TGFβRII receptor inhibited TGFβ in tumors by around 50%, confirming improved tumor localization with BCA101. In PDX models derived from head and neck cancer squamous cell carcinoma patients, BCA101 exerted sustained antitumor effect and delayed tumor growth compared to cetuximab. Finally, BCA101 improved the anti-tumor activity of PD1 blockade therapy in humanized HuNOG-EXL mice bearing PC-3 xenografts (figure 1).Abstract 874 Figure 1BCA101 shows superiority over cetuximab in animal models. (A) & (B). Patient derived xenograft (PDX) models. Patient derived tumors were engrafted into female NOG mice. Once tumor reached about 130 mm3, mice were randomized into control and test groups. Test group mice were treated with either BCA101 (A) or cetuximab (B), thrice a week (i.p), whereas control animals received placebo alone. Mice were treated for 27 days followed by a treatment-free phase until Day 79. Tumor volumes and mice weight were recorded twice a week. (C). BCA101 inhibits FaDu tumor xenograft growth (CDX) in vivo. Nude mice were implanted with FaDu cells on flanks. Once tumor reached about 100 mm3, mice were randomized (n=7) and treated with six doses of test compounds, BCA101 and cetuximab. Tumor volume and mice weight were recorded twice a week. (D). BCA101 and anti-PD1 combination studies in hu-NOG-EXL humanized animal model. PC-3 cells were implanted into flank of Hu-NOG-EXL humanized mice and randomized into control and test groups once tumors reached about 120 mm3. Test group mice were treated with cetuximab or BCA101, intraperitoneally for 6 doses. Anti-PD1 antibody (pembrolizumab) was administered intraperitoneally at a dose of 10 mg/kg with a dosage schedule of every fifth-day for 5 doses (Q5Dx5). Statistical analysis for panel (C) & (D) was performed using repeated measures two-way ANOVA followed by Bonferroni’s multiple comparison test. Significance was indicated by * = p value ≤0.05, ** = p value ≤0.01 and *** = p value ≤0.001. Tumor volumes are presented as Mean ± SEM.ConclusionsThese results support the clinical development of BCA101 as a targeted immunotherapy with the potential to induce improved anti-tumor response with a wider therapeutic window, either as a monotherapy or in combination with immune checkpoint blockade therapy.AcknowledgementsWe acknowledge Mazumdar Shaw Center for Translational Research for providing the human tissues used for the PDX studies. We thank Syngene International for conducting the PDX and humanized mice studies at their vivarium. We thank Dr. Sreesha Srinivasa for providing suggestions and feedback at the early stages of this project.ReferencesBedi A, Chang X, Noonan K , Pham V, Bedi R, Fertig EJ, Considine M, Califano JA, Borrello I, Chung CH, Sidransky D, Ravi R. Inhibition of TGF-b enhances the in vivo antitumor efficacy of EGF receptor–targeted therapy. Mol Cancer Ther 2012;11:1–11.Yegodayev KM, Novoplansky O, Golden A, Prasad M, Levin L, Jagadeeshan S, Zorea J, Dimitstein O, Joshua B-Z, Cohen L, Khrameeva E, Elkabets M. TGF-Beta-activated cancer-associated fibroblasts limit cetuximab efficacy in preclinical models of head and neck cancer. Cancers 2020;12:1–17.Ethics ApprovalMice were maintained as per the regulations of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India and Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) guidelines. All animal experiments were approved by institutional ethical committee and performed under approved protocols. For PDX model, head and neck cancer patient samples were obtained from Mazumdar Shaw Medical Foundation, Bengaluru, India after appropriate approvals were obtained from institutional ethical committee: NHH/MEC-RC2016-404

Abstract:Objective: To evaluate the relationship between passive smoking and salivary biomarkers like pH, buffering capacity and flow rate, sialic acid and amylase levels in children who were passive smokers and compare with the control group. Materials and Methods: Fifty children with history of passive smoking and 50 healthy age matched controls were included in the study. Details on smoking habits of household members, child's dental and dietary habits were collected using a proforma. Saliva samples were collected from both the groups and salivary analysis was done for pH, buffering capacity, flow rate, sialic acid levels and amylase levels. Results:The results of the study showed a lower salivary pH and flow rate with an increase in amylase activity and buffering capacity in passive smoking children when compared to healthy controls. However, sialic acid levels did not show significant differences between passive smoking children and control group. Conclusion: Passive smoking may reduce the protective properties of saliva which can further affect the oral health status of young children and any factor that influences the secretion rate or composition of saliva will ultimately influence caries susceptibility.