Systematic assessment of HER2/neu in gynecologic neoplasms, an institutional experience.

BackgroundHER2/neu overexpression and/or amplification has been widely studied in a number of solid tumors, primarily in the breast. In gynecologic neoplasms, determination of HER2/neu status has not been well studied as a predictive biomarker in anti-HER2/neu treatment.MethodsWe systematically evaluated the HER2/neu reactions by immunohistochemistry and fluorescent in situ hybridization in malignant gynecologic neoplasms as experienced in our institution.ResultsThe HER2/neu overexpression or amplification occurred in 8 % of the cancers of the gynecological organs in our series. Majority of the HER2/neu overexpression and/or amplification occurred in clear cell (27 %) and serous (11 %) carcinomas. HER2/neu positivity was also seen in undifferentiated as well as in mixed clear cell and serous carcinomas. Discordant IHC and FISH results (positive by FISH but not IHC) was seen in 2 cases. Majority of the HER2/neu overexpression and/or amplification occurs in the endometrium rather than the ovary. Heterogeneity of the HER2/neu by IHC staining was in < 2 % of the tumors in our series.ConclusionsWe recommend the HER2/neu studies on Müllerian carcinomas of clear cell, serous, and undifferentiated types, particularly when they arise in the endometrium. Since there are some discordant IHC/FISH results, we also propose performing the HER2/neu testing by FISH when the IHC score is less than 3 + 

Estradiol regulates miR-135b and mismatch repair gene expressions via estrogen receptor-β in colorectal cells.

Estrogen has anti-colorectal cancer effects which are thought to be mediated by mismatch repair gene (MMR) activity. Estrogen receptor (ER) expression is associated with microRNA (miRNA) expression in ER-positive tumors. However, studies of direct link between estrogen (especially estradiol E2), miRNA expression, and MMR in colorectal cancer (CRC) have not been done. In this study, we first evaluated the effects of estradiol (E2) and its antagonist ICI182,780 on the expression of miRNAs (miR-31, miR-155 and miR-135b) using COLO205, SW480 and MCF-7 cell lines, followed by examining the association of tissue miRNA expression and serum E2 levels using samples collected from 18 colorectal cancer patients. E2 inhibited the expressions of miRNAs in COLO205 cells, which could be reversed by E2 antagonist ICI 182.780. The expression of miR-135b was inversely correlated with serum E2 level and ER-β mRNA expression in CRC patients' cancer tissues. There were significant correlations between serum E2 level and expression of ER-β, miR-135b, and MMR in colon cancer tissue. This study suggests that the effects of estrogen on MMR function may be related to regulating miRNA expression via ER-β, which may be the basis for the anti-cancer effect in colorectal cells

miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis

Stratospheric PULSE–continental cold air outbreak coupling relationships: Interannual and interdecadal changes

Stratospheric processes and their role in weather and climate have attracted increasing interests. The correspondence between the occurrence of pulse-like, stronger stratospheric poleward warm airmass transport (PULSE) events and the continental-scale cold air outbreak (CAO) events in northern hemispheric winter is found to be unstable from year to year. This increases the difficulties in utilizing the more predictable stratospheric variability in the sub-seasonal forecasts of CAOs, which can cause cold hazards. Using the ERA5 reanalysis data covering 37 winters (November–March) in the period 1979–2015, this study categorizes the CAO events over mid-latitudes of Eurasia (CAO_EA) and those over North America (CAO_NA) into two groups: those coupled with and those decoupled with the PULSE events. The coupled CAOs are further categorized into events that are, respectively, lead-coupled and lag-coupled with PULSEs. The intensity and affected area of extremely cold temperatures tend to be larger during CAOs that are coupled with PULSEs, particularly during the CAO_NA events that are lag-coupled with PULSEs and the CAO_EA events that are lead-coupled with PULSEs. Remarkable interannual and interdecadal variations are observed in the percentage of CAOs that are coupled with PULSEs for each winter, which is an important reference for determining the window of opportunity for skillful sub-seasonal forecasts of CAO by using the stratospheric signals. At both interdecadal and interannual timescales, a warm phase of the El Niño–Southern Oscillation (ENSO) in winter is favorable for the higher lag-coupling rate of CAO_NA and the lead-coupling rate of CAO_EA, and vice versa. The ENSO signals related to the interdecadal changes of the CAO coupling rate in winter can be traced back to the previous winter, while an ENSO phase transition from the previous winter to the current winter is closely related to the interannual changes of the CAO coupling rate

Insights into the Ecological Roles and Evolution of Methyl-Coenzyme M Reductase-Containing Hot Spring Archaea

Several recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor

Paraholcoglossum and Tsiorchis, Two New Orchid Genera Established by Molecular and Morphological Analyses of the Holcoglossum Alliance

BACKGROUND: Holcoglossum is a small orchid genus of 12 species ranging from SW China to Thailand and NE India. Although molecular and morphological analyses have been performed to establish the phylogenetic relationships within this genus, the interspecific relations and its relations with allied genera, such as Rhynchostylis, Aerides and Vanda, remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In addition to morphological analysis, maximum parsimony, maximum likelihood, and Bayesian inference analyses were performed based on fragments of the nuclear ITS and chloroplast trnL-F and matK genes of 31 taxa (15 Holcoglossum, 14 Aeridinae, 2 outgroups) representing all major clades of the Holcoglossum alliance. The results suggest that Holcoglossum is triphyletic, comprising three clades: the Holcoglossum clade, its sister clade, and a distant clade more closely related to Rhynchostylis, Aerides, and Vanda than to the Holcoglossum clade. The Holcoglossum clade is further divided into three subclades; the genetic distances between these three subclades also support this delimitation. The molecular conclusion is consistent with their distinct morphological characters. CONCLUSIONS: We propose that the latter two clades comprise two new genera, Paraholcoglossum and Tsiorchis, and Holcoglossum clade divides into three sections. In addition, a new section, Holcoglossum sect. Nujiangensia, and a new species, Holcoglossum linearifolium, are proposed. Some new combinations are made, and a new scheme is provided for the classification of all species of Holcoglossum, Paraholcoglossum, and Tsiorchis

Neottia bifidus (Orchidaceae, Epidendroideae, Neottieae), a new mycoheterotrophic species from Guizhou, China

Neottia bifidus, a new mycoheterotrophic orchid, found in Maolan National Nature Reserve in Guizhou Province, China, is described and illustrated here. The new species is close to N. nidus-avis, N. kiusiana and N. papilligera but differs in having a finely pubescent rachis with fewer flowers, a finely pubescent pedicel, and a fishtail-shaped lip that is deeply bilobed to the middle of the lip, with the lobes diverging at an acute angle (45°) to each other and mesochile with many papillae. Additionally, N. bifidus is well supported as a new species by molecular phylogenetic results based on ITS and chloroplast genome. The chloroplast genome of the novelty, which contains an LSC region of 33,819 bp, SSC region of 5,312 bp and IRs of 46,762 bp was assembled and annotated. A key to mycoheterotrophic Neottia species in China is also provided