In this prospective randomized trial, hENT1 protein expression was associated with increased overall survival and disease-free survival in pancreatic cancer patients who received gemcitabine, but not in those who received 5-FU. These findings are supported by preclinical data; the gemcitabine transporter hENT1 is therefore a molecular and mechanistically relevant predictive marker of benefit from gemcitabine in patients with resected pancreatic cancer.

BACKGROUND: Hypoxia, which is commonly observed in areas of primary tumours and of metastases, influences response to treatment. However, its characterisation has so far mainly been restricted to the ex vivo analysis of tumour sections using monoclonal antibodies specific to carbonic anhydrase IX (CA IX) or by pimonidazole staining, after the intravenous administration of this 2-nitroimidazole compound in experimental animal models. METHODS: In this study, we describe the generation of high-affinity human monoclonal antibodies (A3 and CC7) specific to human CA IX, using phage technology. RESULTS: These antibodies were able to stain CA IX ex vivo and to target the cognate antigen in vivo. In one of the two animal models of colorectal cancer studied (LS174T), CA IX imaging closely matched pimonidazole staining, with a preferential staining of tumour areas characterised by little vascularity and low perfusion. In contrast, in a second animal model (SW1222), distinct staining patterns were observed for pimonidazole and CA IX targeting. We observed a complementary pattern of tumour regions targeted in vivo by the clinical-stage vascular-targeting antibody L19 and the anti-CA IX antibody A3, indicating that a homogenous pattern of in vivo tumour targeting could be achieved by a combination of the two antibodies. CONCLUSION: The new human anti-CA IX antibodies are expected to be non-immunogenic in patients with cancer and may serve as broadly applicable reagents for the non-invasive imaging of hypoxia and for pharmacodelivery applications.

In the recent worldwide coronavirus 2019 pandemic, a notable rise in pneumomediastinum and pneumothorax complications has been witnessed in numerous mechanically ventilated patients infected with severe acute respiratory syndrome coronavirus 2. Most cases have reported these complications as barotrauma from mechanical ventilation with COVID-19 disease. We aim to report three polymerase chain reaction-confirmed COVID-19 patients who developed pneumomediastinum and pneumothorax unrelated to mechanical ventilation. We originally analyzed 800 patients with COVID-19 disease at Orlando Regional Medical Center from March 1, 2020, to July 31, 2020, of which 12 patients developed pneumomediastinum and pneumothorax in their hospital course. Interestingly, three patients developed pneumomediastinum on chest imaging prior to intubation. We present these three patients, one female and two males, ages of 42, 64, and 65, respectively, who were diagnosed with COVID-19 disease through nasopharyngeal sampling tests with acute respiratory distress syndrome. Spontaneous pneumomediastinum and pneumothorax are potential complications of COVID-19 disease in the lungs unrelated to mechanical ventilation. This is similar to previous outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) diseases. Further investigation is needed to define the causality of pneumomediastinum in nonintubated COVID-19 patients to define the incidence of disease.