A novel inhibitory anti-invasive MAb isolated using phenotypic screening highlights AnxA6 as a functionally relevant target protein in pancreatic cancer.

BACKGROUND: Discovery and validation of new antibody tractable targets is critical for the development of new antibody therapeutics to address unmet needs in oncology. METHODS: A highly invasive clonal variant of the MDA-MB-435S cell line was used to generate monoclonal antibodies (MAbs), which were screened for anti-invasive activity against aggressive cancer cells in vitro. The molecular target of selected inhibitory MAb 9E1 was identified using immunoprecipitation/liquid chromatography-tandem mass spectrometry. The potential anti-tumour effects of MAb 9E1 were investigated in vitro together with immunohistochemical analysis of the 9E1 target antigen in normal and cancer tissues. RESULTS: MAb 9E1 significantly decreases invasion in pancreatic, lung squamous and breast cancer cells and silencing of its target antigen, which was revealed as AnxA6, leads to markedly reduced invasive capacity of pancreatic and lung squamous cancer in vitro. IHC using MAb 9E1 revealed that AnxA6 exhibits a high prevalence of membrane immunoreactivity across aggressive tumour types with restricted expression observed in the majority of normal tissues. In pancreatic ductal adenocarcinoma, high AnxA6 IHC score correlated with the presence of tumour budding at the invasive front of tumours (P=0.082), the presence of perineural invasion (P= <0.0001) and showed a weak correlation with reduced survival (P=0.2242). CONCLUSIONS: This study highlights the use of phenotypic hybridoma screening as an effective strategy to select a novel function-blocking MAb, 9E1 with anti-cancer activity in vitro. Moreover, through characterisation of the 9E1 target antigen, AnxA6, our findings support further investigation of AnxA6 as a potential candidate target for antibody-mediated inhibition of pancreatic cancer.

Unusual childhood presentations of abdominal non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) is a relatively common childhood cancer that can present in a myriad of ways. It is essential that NHL is included in the differential diagnosis of children presenting with an abdominal complaint, especially those with unexplained or prolonged symptoms. We describe three acute pediatric presentations of abdominal NHL, two of which presented as acute abdomen (the first mimicking intussusception and the second appendicitis), and the third involving lower limb edema. This case series illustrates the array of presentations of abdominal NHL and the diagnostic challenges that they can provide.

The role of endomyocardial biopsy in suspected myocarditis in the contemporary era: a 10-year National Transplant Centre experience.

BACKGROUND: Diagnostic endomyocardial biopsy (EMB) in patients with suspected myocarditis helps to direct therapy and guide prognosis. This study aimed to investigate the correlation between the 2007 clinical guideline indications for EMB and the presence of a diagnostic biopsy result and associated outcomes in patients with suspected myocarditis in a national quaternary referral center in a contemporary cohort. METHODS: All cases of suspected myocarditis referred to the National Cardiac Transplant Centre who underwent EMB between 2009 and 2019 were identified retrospectively through pathology records. Outcomes including subsequent need for inotrope and/or mechanical circulatory support (MCS), heart transplantation and in-hospital mortality were recorded. RESULTS: In total, 25 (68% male, mean age of 45 ± 15 years) EMBs were performed for this indication across this time period, 64% (n = 16) of which demonstrated diagnostic results, the majority (75%, n = 12) identifying acute lymphocytic myocarditis, 13% (n = 2) giant cell, one patient (6.3%) eosinophilic and one (6.3%) an immune checkpoint inhibitor myocarditis. The majority of those with histologically confirmed myocarditis had a Class I or IIa guideline indication for EMB (n = 12, 75%). The remaining 4 patients (25%), either met Class IIb criteria (n = 2) or would not have been accounted for in this guideline. The majority of patients requiring inotropes and/or MCS (n = 9/11), and/or heart transplant (n = 3/4), or who later died (n = 4/5) were in the diagnostic biopsy group. CONCLUSIONS: In this 10-year National referral sample, 75% of patients with histologically confirmed myocarditis had a Class I or IIa indication for EMB, reinforcing the usefulness of traditional guidelines in this contemporary era. However, 25% of patients with a subsequent confirmed histological diagnosis had either none or a less well-established indication for EMB, highlighting the need for clinical suspicion outside of accepted clinical scenarios.

Mandibular swelling in a 5-year-old child--mandibular myofibroma.

A 5-year-old girl of African descent presented with a history of progressive painless swelling on the right side of the jaw since the past 2-3 months. Orthopantomogram showed a radiolucent lesion near the angle of the mandible. Subsequent CT scan revealed a 2 cm×2 cm radiolucent lesion with intense periosteal reaction surrounding the lesion and destruction of the overlying cortex. Radiological perplexity aroused regarding the possibility of eosinophilic granuloma or some other malignant lesion. Incisional biopsy performed and microscopy showed spindle cell tumor. Immunohistochemistry confirmed it as myofibroma. Myofibroma is a rare benign tumour involving mesenchyme. Involvement of the mandible is rare. Radiological presentation with strong periosteal reaction is a rarity and has rarely been reported in the medical literature. We conclude that intraosseous myofibroma can sometimes have strong periosteal reaction and careful radiological evaluation is a prerequisite for accurate diagnosis and to avoid unnecessary aggressive therapy.