1,1′-(Butane-1,4-diyl)di-1H-imidazole–benzene-1,3,5-triol–water (1/1/1)

The asymmetric unit of the title compound, C10H14N4·C6H6O3·H2O, contains one mol­ecule of benzene-1,3,5-triol, two half-molecules of 1,1′-butane-1,4-diyldi-1H-imidazole (each molecule is centrosymmetric) and one solvent water mol­ecule. In the crystal structure, inter­molecular O—H⋯O and O—H⋯N hydrogen bonds link all mol­ecules into a three-dimensional supra­molecular network

Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells.

IntroductionAlthough breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors.MethodsParaffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation.ResultsImmunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment. Moreover, we provided the first evidence for the induction of ALDH+/GD2+ cells to differentiate into neural cells of various lineages, along with the observation of neural differentiation in clinical specimens and xenografts of malignant phyllodes tumors. ALDH+ or ALDH+/GD2+ cells could also be induced to differentiate into adipocytes, osteocytes or chondrocytes.ConclusionsOur findings revealed that malignant phyllodes tumors possessed many characteristics of MSC, and their CSCs were enriched in ALDH+ and ALDH+/GD2+ subpopulations

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

Dichlorido{[2-(diphenyl­phosphino)phenyl­imino­meth­yl]ferrocene-κ2 N,P}platinum(II) dichloro­methane hemisolvate

In the title compound, [FePt(C5H5)(C24H19NP)Cl2]·0.5CH2Cl2, the PtII atom adopts a distorted square-planar geometry defined by one P atom and one N atom from the bidentate [2-(diphenyl­phosphino)phenyl­imino­meth­yl]ferro­cene ligand and two Cl atoms. Two disordered dichloro­methane solvent mol­ecules are each 0.25-occupied on a twofold rotation axis

FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.

BackgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.MethodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.FindingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.InterpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan)

Angiogenesis and Vasculogenesis at 7-Day of Reperfused Acute Myocardial Infarction

Objectives 
This study is to investigate the angiogenesis and vasculogenesis at the first week of reperfused acute myocardial infarction (AMI).
Methods 
16 of mini-swines (20 to 30 Kg) were randomly assigned to the sham-operated group and the AMI group. The acute myocardial infarction and reperfusion model was created and the pig tail catheter was performed to monitor hemodynamics before left anterior descending coronary artery (LAD) occlusion, 90 min of LAD occlusion and 120 min of LAD reperfusion. Pathologic myocardial tissue was collected at 7-day of LAD reperfusion and further assessed by immunochemistry, dual immunochemistry, in-situ hybridization, real-time quantitative polymerase chain reaction and western blot. 
Results 
The infarcted area had higher FLK1 mRNA expression than sham-operated area and the normal area (all P<0.05), and the infarcted and marginal areas showed higher CD146 protein expression than the sham-operated area (all P<0.05), but the microvessel density (CD31 positive expression of microvessels/HP) was not significantly different between the infarcted area and the sham-operated area (8.92±3.05 vs 6.43±1.54) at 7-day of reperfused acute myocardial infarction (P>0.05). 
Conclusions 
FLK1 and CD146 expression significantly increase in the infarcted and marginal areas, and the microvessel density is not significantly different between the infarcted area and the sham-operated area, suggesting that angiogenesis and vasculogenesis in the infarcted area appear to high frequency of increase in 7-day of reperfused myocardial infarction. 
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