11 research outputs found
Mutational and gene fusion analyses of primary large cell and large cell neuroendocrine lung cancer.
Large cell carcinoma with or without neuroendocrine features (LCNEC and LC, respectively) constitutes 3-9% of non-small cell lung cancer but is poorly characterized at the molecular level. Herein we analyzed 41 LC and 32 LCNEC (including 15 previously reported cases) tumors using massive parallel sequencing for mutations in 26 cancer-related genes and gene fusions in ALK, RET, and ROS1. LC patients were additionally subdivided into three immunohistochemistry groups based on positive expression of TTF-1/Napsin A (adenocarcinoma-like, n = 24; 59%), CK5/P40 (squamous-like, n = 5; 12%), or no marker expression (marker-negative, n = 12; 29%). Most common alterations were TP53 (83%), KRAS (22%), MET (12%) mutations in LCs, and TP53 (88%), STK11 (16%), and PTEN (13%) mutations in LCNECs. In general, LCs showed more oncogene mutations compared to LCNECs. Immunomarker stratification of LC revealed oncogene mutations in 63% of adenocarcinoma-like cases, but only in 17% of marker-negative cases. Moreover, marker-negative LCs were associated with inferior overall survival compared with adenocarcinoma-like tumors (p = 0.007). No ALK, RET or ROS1 fusions were detected in LCs or LCNECs. Together, our molecular analyses support that LC and LCNEC tumors follow different tumorigenic paths and that LC may be stratified into molecular subgroups with potential implications for diagnosis, prognostics, and therapy decisions
Ocean Acidification at High Latitudes: Potential Effects on Functioning of the Antarctic Bivalve Laternula elliptica
Ocean acidification is a well recognised threat to marine ecosystems. High
latitude regions are predicted to be particularly affected due to cold waters
and naturally low carbonate saturation levels. This is of concern for organisms
utilising calcium carbonate (CaCO3) to generate shells or skeletons.
Studies of potential effects of future levels of pCO2 on high latitude
calcifiers are at present limited, and there is little understanding of their
potential to acclimate to these changes. We describe a laboratory experiment
to compare physiological and metabolic responses of a key benthic bivalve, Laternula
elliptica, at pCO2 levels of their natural environment
(430 µatm, pH 7.99; based on field measurements) with those predicted
for 2100 (735 µatm, pH 7.78) and glacial levels (187 µatm, pH
8.32). Adult L. elliptica basal metabolism (oxygen consumption
rates) and heat shock protein HSP70 gene expression levels
increased in response both to lowering and elevation of pH. Expression of
chitin synthase (CHS), a key enzyme involved in synthesis
of bivalve shells, was significantly up-regulated in individuals at pH 7.78,
indicating L. elliptica were working harder to calcify in
seawater undersaturated in aragonite (ΩAr = 0.71),
the CaCO3 polymorph of which their shells are comprised. The different
response variables were influenced by pH in differing ways, highlighting the
importance of assessing a variety of factors to determine the likely impact
of pH change. In combination, the results indicate a negative effect of ocean
acidification on whole-organism functioning of L. elliptica
over relatively short terms (weeks-months) that may be energetically difficult
to maintain over longer time periods. Importantly, however, the observed changes
in L. elliptica CHS gene expression provides evidence for
biological control over the shell formation process, which may enable some
degree of adaptation or acclimation to future ocean acidification scenarios
Delayed Hemorrhage From Completely Obliterated Arteriovenous Malformation After Gamma Knife Radiosurgery
A cohort study of the prognostic and treatment predictive value of SATB2 expression in colorectal cancer
BACKGROUND: Special AT-rich sequence-binding protein 2 (SATB2) is a novel diagnostic marker of colorectal cancer (CRC), and loss of SATB2 has been linked to poor survival from the disease. In this study, we validated the prognostic ability of SATB2 expression in a large, prospective CRC cohort. METHODS: Immunohistochemical SATB2 expression was assessed in 527 incident CRC cases from the Malmö Diet and Cancer Study. Kaplan–Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB2 expression on cancer-specific survival (CSS) and overall survival (OS). RESULTS: High SATB2 expression was associated with a prolonged CSS in the full cohort (hazard ratio (HR)=0.61; 95% CI 0.41–0.92) and in colon cancer (HR=0.39; 95% CI 0.20–0.75), remaining significant in multivariable analysis of colon cancer (HR=0.49; 95% CI 0.25–0.96), with similar findings for OS. In curatively resected stage III-IV patients, a significant benefit from adjuvant and/or neoadjuvant therapy was observed for SATB2 high tumours (P(interaction)=0.037 for OS) and high SATB2 expression in rectal cancer correlated with an enhanced effect of neoadjuvant therapy (P(interaction)=0.033 for OS). CONCLUSION: High SATB2 expression is an independent marker of good prognosis in colon cancer and may modulate sensitivity to chemotherapy and radiation
First Case of 2019 Novel Coronavirus in the United States
An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection