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.
The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial and phenotypic ...immune-ITH from multiple tumour sectors and decipher its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune-ITH is associated with tumour transcriptomic-ITH, mutational burden and distinct immune microenvironments. Tumours with low immune-ITH experience higher immunoselective pressure and escape via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH evolve to a more immunosuppressive/exhausted microenvironment. This gradient of immune pressure along with immune-ITH represents a hallmark of tumour evolution, which is closely linked to the transcriptome-immune networks contributing to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature are predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides evidence on tumour-immune co-evolution along HCC progression.
Hepatocellular carcinoma with biliary ductal invasion is rare and associated with a significantly lower survival rate.
We present an unusual case of a patient with hepatocellular carcinoma and ...biliary invasion, who had his diagnosis confirmed by histological analysis from tissue extracted by endoscopic retrograde cholangiopancreatography. An 87-year-old male presented with a 1-day history of right upper quadrant pain and jaundice. His past medical history included recurrent gallstone cholangitis and a previous cholecystectomy. An abdominal CT demonstrated a dilated intrahepatic biliary tree with left proximal intrahepatic hyperdensities, as well as a 3 cm hepatocellular carcinoma. He was initially suspected to have concurrent gallstone cholangitis and a newly diagnosed hepatocellular carcinoma. Endoscopic retrograde cholangiopancreatography and balloon trawling of the intraductal lesions extracted necrotic tumour-like tissue which was histologically consistent with hepatocellular carcinoma. The extraction of the intra-biliary portion of HCC resulted in complete resolution of his jaundice, enabling further treatment with nivolumab, which would not have been possible if the obstruction was not cleared. The patient is currently well and has completed his 6th cycle of nivolumab.
Obstructive jaundice is an uncommon presentation for patients with HCC. it is key for clinicians to be aware of the possibility of intrabiliary invasion in order obtain an early diagnosis and to reduce any delay in treatment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tocilizumab, a monoclonal antibody against interleukin-6, has been used to treat cytokine release syndrome (CRS) in a subset of patients with severe COVID-19 disease. Acute ulcerative bowel disease ...has been only rarely documented in patients treated for rheumatological conditions. The gastrointestinal side effects seen when used in the context of COVID-19 are unknown. We present a case of COVID-19 CRS in which acute terminal ileum and perforated caecal ulceration evolved after tocilizumab exposure. We raise awareness of a possible causal relationship between even a single dose of tocilizumab and gut ulceration in patients with COVID-19. Any such drug enteropathy relationship requires watchful monitoring during upcoming trials of tocilizumab in patients with COVID-19.
Abstract Background Osteoblastoma is rare and accounts for 3% of all benign tumours and 1% of all bone tumours. The spine is the most common site of occurrence, constituting 32 to 45 % of all ...osteoblastomas. It has a strong predilection for the posterior elements, most often occurring in the lumbar spine. Method In this case report, we describe an unusual presentation of spinal osteoblastoma presenting as thoracic T9 vertebra plana in a 20-year-old female. She presented with discomfort over the midback with unsteadiness of gait. The patient underwent detailed investigations including CT, MRI and CT guided Biopsy. To our knowledge, this is the first case report of vertebra plana due to spinal osteoblastoma in the English literature. Result The patient successfully underwent posterior decompression of T9 with laminectomy followed by MIS (Minimally Invasive Surgery) posterior instrumentation from T7 to T11. Histopathology of the intraoperative specimen was consistent with osteoblastoma. The patient had an uneventful postoperative recovery and no evidence of tumour recurrence could be demonstrated on PET scan at 15 months' follow-up. Conclusion In conclusion, the differential diagnosis for vertebra plana is extensive and we add spinal osteoblastoma as another etiology to the existing list. Diagnosis and treatment of vertebra plana involves multimodality radiological imaging, and careful histological and surgical evaluation to identify the underlying etiology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Squamoid cyst of pancreatic duct is a rare benign pancreatic lesion that is rarely encountered in fine‐needle aspiration (FNA) and surgical resection specimens. Pancreatic stones can be seen in ...chronic pancreatitis, but stone‐related crystals have previously not been described in pancreatic cytology. Presented here is a case report of a squamoid cyst of pancreatic duct with concurrent pancreatic duct stones. We describe the cytomorphology of this benign cyst, as well as the remarkable finding of polymorphous crystals on cyst fluid aspirate. We also describe the histology of the surgically resected cystic lesion. With the increase in detection of incidental pancreatic cysts on imaging, this case highlights the importance of awareness and recognition of benign non‐neoplastic epithelial cysts on FNA sampling to avoid overtreatment. The presence of crystals on pancreatic FNA is an unusual finding, likely representing calcium carbonate crystals related to the formation of pancreatic duct stones.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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