While most cancer nanomedicine is designed to eliminate cancer, the nanomaterial per se can lead to the formation of micrometre-sized gaps in the blood vessel endothelial walls. Nanomaterials-induced ...endothelial leakiness (NanoEL) might favour intravasation of surviving cancer cells into the surrounding vasculature and subsequently extravasation, accelerating metastasis. Here, we show that nanoparticles induce endothelial leakiness through disruption of the VE-cadherin-VE-cadherin homophilic interactions at the adherens junction. We show that intravenously injected titanium dioxide, silica and gold nanoparticles significantly accelerate both intravasation and extravasation of breast cancer cells in animal models, increasing the extent of existing metastasis and promoting the appearance of new metastatic sites. Our results add to the understanding of the behaviour of nanoparticles in complex biological systems. The potential for NanoEL needs to be taken into consideration when designing future nanomedicines, especially nanomedicine to treat cancer.
Identification of the factors critical to the tumor-initiating cell (TIC) state may open new avenues in cancer therapy. Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical ...for TICs in non-small cell lung cancer (NSCLC). TICs from primary NSCLC tumors express high levels of the oncogenic stem cell factor LIN28B and GLDC, which are both required for TIC growth and tumorigenesis. Overexpression of GLDC and other glycine/serine enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. We found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. In the clinic, aberrant activation of GLDC correlates with poorer survival in lung cancer patients, and aberrant GLDC expression is observed in multiple cancer types. This link between glycine metabolism and tumorigenesis may provide novel targets for advancing anticancer therapy.
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► Non-small cell lung cancer (NSCLC) tumor-initiating cells express high levels of glycine decarboxylase (GLDC) ► GLDC is an oncogene that promotes cellular transformation ► GLDC activity regulates pyrimidine metabolism in cancer cells ► GLDC expression predicts mortality in NSCLC patients
An enzyme involved in glycine metabolism acts as an oncogene to drive cancer stem cell proliferation and tumorigenesis in non-small cell lung cancer. Aberrant expression of this enzyme occurs in many cancers and correlates with mortality in lung cancer.
Abstract
Moderate hypothermia (32 °C) has been previously shown to ameliorate drug-induced liver injuries in vitro. However, there are concerns regarding its clinical relevance as it remains a ...challenge to perform selective liver cooling in a non-invasive manner. To reconcile this dilemma, we propose the use of pulsed cooling for regional hypothermic conditioning in liver. This involves intermittent cooling applied in pulses of 15 min each, with a one-hour recovery interval between pulses. Cooling is achieved by applying ice packs to the cutaneous region overlying the liver. Through an in vivo C57BL/6NTac mouse study, we demonstrated the feasibility of attaining localized hypothermia close to the liver while maintaining core body temperature. This has successfully ameliorated acetaminophen-induced liver injury based on the liver function tests, liver histology and total weight change. Collectively, we provide a proof of concept for pulsed external localized cooling as being clinically actionable to perform induced selective hypothermia.
The tumour-initiating cell (TIC) model accounts for phenotypic and functional heterogeneity among tumour cells. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, ...and may contribute towards tumour heterogeneity and TIC behaviour. More recent efforts have focused on miRNAs as diagnostic or therapeutic targets. Here, we identified the TIC-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumour initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumour-initiating potential of TICs and their ability to metastasize. Longitudinal analyses of serum miR-1246 and miR-1290 levels across time correlate their circulating levels to the clinical response of lung cancer patients who were receiving ongoing anti-neoplastic therapies. Functionally, direct inhibition of either miRNA with locked nucleic acid administered systemically, can arrest the growth of established patient-derived xenograft tumours, thus indicating that these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets.
Background
The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) aims to provide a common language for risk stratification and management. We examine the incidence of MSRSGC categories ...and the corresponding risk of malignancy (ROM) within a tertiary referral centre in Southeast Asia.
Methods
Salivary gland fine needle aspirations (FNAs) performed within a 10‐year period were classified retrospectively according to the MSRSGC. Cytohistologic correlation was performed. The results were compared with the existing literature, including Asian and Western studies.
Results
A total of 1384 salivary gland FNAs were evaluated, 421 with corresponding histology. The category distribution was: nondiagnostic, 28.9%; nonneoplastic, 18.0%; atypia of undetermined significance (AUS), 9.8%; benign neoplasm, 32.9%; salivary gland neoplasm of uncertain malignant potential (SUMP), 5.7%; suspicious for malignancy, 1.6%; and malignant, 3.2%. The ROMs were: nondiagnostic, 10.0%; nonneoplastic, 17.5%; AUS, 29.5%; benign neoplasm, 0.5%; SUMP, 17.1%; suspicious for malignancy, 83.3%; and malignant, 100.0%. Our relatively high nondiagnostic rate likely reflects preanalytical factors, whereas our low malignancy rate may be related to population and health care accessibility. Our nonneoplastic ROM was 17.5% compared with 5% to 10% in the literature, likely due to the relatively small number of excised cases; the ROM for SUMP was 17.1% versus 21% to 44% in the literature, possibly reflecting a significant proportion of benign basaloid neoplasms on histology. Interestingly, all false‐negative cases in the nonneoplastic category were lymphoid‐rich lesions.
Conclusion
This is one of the largest single‐institution studies in the existing literature documenting both the incidence and ROMs of MSRSGC categories. We also highlight specific challenges surrounding lymphoid‐rich lesions.
This article presents the incidence and corresponding risk of malignancy of diagnostic categories in salivary gland fine needle aspirations, using The Milan System for Reporting Salivary Gland Cytopathology, within a tertiary referral center in Southeast Asia. The data are compared with the current literature, with a discussion of differences as well as challenges in reporting fine needle aspirations of salivary gland lesions.
The coronavirus COVID‐19 pandemic has spurred the rapid development of vaccines, with vaccination programmes already underway in many countries. Regional lymphadenopathy is one of the documented side ...effects of vaccination. We document the fine needle aspiration cytological findings of an enlarged supraclavicular lymph node in a 34‐year‐old Asian female following the first dose of the Pfizer‐BioNTech COVID‐19 mRNA vaccine, which appears to be the first such report in a premorbidly well patient with no known history of malignancy. The cytological findings featured a reactive pattern in keeping with follicular hyperplasia, with prominent germinal centre elements including lymphohistiocytic aggregates and tingible‐body macrophages. Despite an increased proportion of larger lymphocytes, the overall pattern was in keeping with a reactive pattern, bearing in mind the temporal and geographic relation to the vaccination injection. In instances of localised lymphadenopathy, particularly in supraclavicular or axillary locations, pathologists should be cognizant of the possibility of post‐vaccination reactive lymphadenopathy, and seek clinical and radiological hints favouring a benign process, whilst recognising potential morphological overlaps with lymphoproliferative disorders. Awareness of this diagnostic pitfall is especially important as COVID‐19 vaccination coverage is ramped up worldwide, leading to an expected increase in incidence of post‐vaccination reactive lymphadenopathy.
We describe a case of papillary thyroid carcinoma with fibromatosis/fasciitis-like stroma (PTC-FLS) that contained the rare
BRAF
c.1799_1801delTGA (p.V600_K601delinsE) mutation, which has not ...previously been reported in this tumour, as well as the
CTNNB1
c.133T>C (p.S45P) mutation. We also report the novel observation that spindle cells of the mesenchymal component exhibit diffuse nuclear but not cytoplasmic expression of SOX11, whereas the malignant epithelial cells did not. This suggests that immunoreactivity for SOX11 can be an alternative diagnostic tool for evaluating cases of PTC-FLS where the nuclear expression of β-catenin is ambiguous.
Background
Thyroxine replacement following a hemithyroidectomy is not commonly discussed during consent for the procedure as the risk of hypothyroidism is perceived to be low.
Methods
Retrospective ...review of 901 patients who underwent hemithyroidectomy at a tertiary referral institution during the period January 2000 to December 2015. The main outcome studied was the overall incidence of hypothyroidism and the associated risk factors.
Results
Hypothyroidism developed in 123 (13%) patients and 94 patients (10%) required hormone supplementation over a mean follow up of 21 months (range 1‐168 months). Preoperative TSH of more than 2.5 was seen in 38 of 123 (31%) of patients. Presence of diffuse thyroiditis was the only independent risk factor on multivariate analysis (P = 0.002) found to be associated with the development of hypothyroidism.
Conclusion
After thyroid lobectomy, approximately one in 10 patients requiring thyroid hormone treatment for hypothyroidism. Presence of diffuse thyroiditis is a significant risk factor for hypothyroidism.
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