Members of the epidermal growth factor receptor, EGFR, family are interesting as targets for radionuclide therapy using targeting agents labeled with α- or β-emitting radionuclides, especially when EGFR-positive colorectal carcinomas, CRC, are resistant to EGFR inhibiting agents like cetuximab and various tyrosine kinase inhibitors. The expression of EGFR, HER2 and HER3 was therefore analyzed in CRC samples from primary tumors, corresponding lymph node metastases and, in a few cases, liver metastases. The expression of HER2 and EGFR was scored from immunohistochemical preparations using the HercepTest criteria 0, 1+, 2+ or 3+ for cellular membrane staining while HER3 expression was scored as no, weak or strong cytoplasm staining. Material from 60 patients was analyzed. The number of EGFR 2+ or 3+ positive primary tumors was 16 out of 56 (29%) and for lymph node metastases 8 out of 56 (14%) whereas only one out of nine (11%) liver metastases were positive. Thus, there was lower EGFR positivity in the metastases. Only one among 53 patients was strongly HER2 positive and this in both the primary tumor and the metastasis. Eight out of 49 primary tumors (16%) were strongly HER3 positive and the corresponding numbers for lymph node metastases were 9 out of 49 (18%) and for liver metastases 2 out of 9 (22%). The observed number of strongly EGFR positive cases was somewhat low but EGFR might be, for the cases with high EGFR expression in metastases, a target for radionuclide therapy. HER2 seems not to be of such interest due to rare expression, neither HER3 due to mainly expression in the cytoplasm. The requirements for successful EGFR targeted radionuclide therapy are discussed, as well as patient inclusion criteria related to radionuclide therapy.

The long non-coding RNA Hox transcript antisense intergenic RNA (HOTAIR) was recently implicated in breast cancer metastasis and is predictive of poor prognosis in colorectal and pancreatic cancers. We recently discovered that HOTAIR is a cell cycle-related lncRNA in human glioma, and its expression is closely associated with glioma staging and poor prognosis. Although lysine specific demethylase 1 (LSD1) and polycomb repressive complex 2 (PRC2) have been demonstrated to be functional targets of HOTAIR, how HOTAIR regulates glioma cell cycle progression remains largely unknown. In this study, we found that EZH2 (predominant PRC2 complex component) inhibition blocked cell cycle progression in glioma cells, consistent with the effects elicited by HOTAIR siRNA. However, the inhibition of LSD1 did not affect cell cycle progression in glioma cells. These results suggest that HOTAIR might regulate cell cycle progression through EZH2. Our intracranial mice model also revealed delayed tumor growth in HOTAIR siRNA- and EZH2 inhibitor-treated groups. Moreover, in HOTAIR knock-down cell lines, the expression of the PRC2-binding domain of HOTAIR (5′ domain) but not of the LSD1-binding domain of HOTAIR (3′ domain) resulted in accelerated cell cycle progression. In conclusion, HOTAIR promotes cell cycle progression in glioma as a result of the binding of its 5′ domain to the PRC2 complex.

No abstract

HOTAIR is a negative prognostic factor and is overexpressed in multiple human cancers including glioblastoma multiform (GBM). Survival analysis of Chinese Glioma Genome Atlas (CGGA) patient data indicated that high HOTAIR expression was associated with poor outcome in GBM patients. NLK (Nemo-like kinase), a negative regulator of the β-catenin pathway, was negatively correlated with HOTAIR expression. When the β-catenin pathway was inhibited, GBM cells became susceptible to cell cycle arrest and inhibition of invasion. Introduction of the HOTAIR 5′ domain in human glioma-derived astrocytoma induced β-catenin. An intracranial animal model was used to confirm that HOTAIR depletion inhibited GBM cell migration/invasion. In the orthotopic model, HOTAIR was required for GBM formation in vivo. In summary, HOTAIR is a potential therapeutic target in GBM.

Hyperspectral (every 5 nm) absorption coefficients of "pure" seawater in the range of 350-550 nm are derived from remote sensing reflectance measured in oligotrophic oceans. The absorption spectrum is reduced by ∼50-70% for the 350-400-nm range and ∼5-10% for the 510-530-nm range compared with the commonly adopted standard for ocean color processing and shows different spectral curvatures. The application of this new spectrum resulted in better retrievals of the phytoplankton absorption coefficient in oligotrophic oceans and will provide better closure of remote sensing reflectance for the UV-visible domain.

An approach to semianalytically derive waters' inherent optical properties (IOPs) from remote sensing reflectance (Rrs) and at the same time to take into account the residual errors in satellite Rrs is developed for open‐ocean clear waters where aerosols are likely of marine origin. This approach has two components: (1) a scheme of combining a neural network and an algebraic solution for the derivation of IOPs, and (2) relationships between Rrs residual errors at 670 nm and other spectral bands. This approach is evaluated with both synthetic and Sea‐viewing Wide Field‐of‐view Sensor (SeaWiFS) data, and the results show that it can significantly reduce the effects of residual errors in Rrs on the retrieval of IOPs, and at the same time remove partially the Rrs residual errors for “low‐quality” and “high‐quality” data defined in this study. Furthermore, more consistent estimation of chlorophyll concentrations between the empirical blue‐green ratio and band‐difference algorithms can be derived from the corrected “low‐quality” and “high‐quality” Rrs. These results suggest that it is possible to improve both data quality and quantity of satellite‐retrieved Rrs over clear open‐ocean waters with a step considering the spectral relationships of the residual errors in Rrs after the default atmospheric correction procedure and without fixing Rrs at 670 nm to one value for clear waters in a small region such as 3 × 3 box.

Various empirical relationships have been developed in the past nine decades to link the Secchi‐disk depth (ZSD) with the diffuse attenuation coefficient (KPAR), the euphotic zone depth (Zeu), and chlorophyll (Chl) concentration, where the latter two are important for the quantification and evaluation of photosynthesis in aquatic environments. There was also a classical theory regarding Secchi‐disk sighting, but large gaps existed between the observations and model outcomes. These gaps have puzzled the ocean community for > 60 yr and have resulted in contradictory conclusions regarding the interpretation and usefulness of ZSD. Here, we compare these measurements with data simulated based on an innovative theory and model regarding ZSD, and we found remarkable agreements between theoretical predictions and these century‐long observations. The results not only resolve the long‐standing puzzles associated with these observations, but also unify the relationships published in the literature. In particular, the ratio of Zeu to ZSD is found to be ∼ 3.5 for all waters, which is ∼ 45% greater than the consensus value of ∼ 2.4 suggested in the past for clear waters. In addition, the new model validates an empirical relationship between ZSD and Chl developed for global oceanic waters, thus providing strong support for using historical ZSD data to study changes of phytoplankton in global oceans in the past century.

Homeobox (HOX) genes, including HOXA13, are involved in human cancer. We found that HOXA13 expression was associated with glioma grade and prognosis. Bioinformatics analysis revealed that most of the HOXA13-associated genes were enriched in cancer-related signaling pathways and mainly involved in the regulation of transcription. We transfected four glioma cell lines with Lenti-si HOXA13. HOXA13 increased cell proliferation and invasion and inhibited apoptosis. HOXA13 decreased β-catenin, phospho-SMAD2, and phospho-SMAD3 in the nucleus and increased phospho-β-catenin in the cytoplasm. Furthermore, downregulation of HOXA13 in orthotopic tumors decreased tumor growth. We suggest that HOXA13 promotes glioma progression in part via Wnt- and TGF-β-induced EMT and is a potential diagnostic biomarker for glioblastoma and an independent prognostic factor in high-grade glioma.