Papillary renal cell carcinoma with metastatic laparoscopic port site and vaginal involvement: a case report

10.1186/1752-1947-5-131Journal of Medical Case Reports513

Prophylactic Embolization of the Cystic Artery Before Radioembolization: Feasibility, Safety, and Outcomes

PurposeTo evaluate the safety and efficacy of two different methods of proximal cystic artery embolization in patients undergoing yttrium-90 radioembolization.Materials and methodsForty-six patients had cystic artery embolization performed immediately before yttrium-90 radioembolization, either by using Gelfoam pledgets (n = 35) or coils (n = 11). Clinical symptomatology during the admission and angiographic findings at 1-month follow-up were retrospectively reviewed. Rates of collateralization or recanalization of the cystic artery were compared, as well as the frequency of postprocedural abdominal pain and need for cholecystectomy.ResultsTechnical success was achieved in all patients, and there were no procedural complications related to cystic artery embolization. Of the 11 coil-embolized patients, 5 (45%) demonstrated collateralization of the cystic artery at 1 month, and 1 (9%) demonstrated recanalization of the cystic artery. Of the 35 Gelfoam-embolized cases, 2 (6%) had collateralized at 1 month, and 14 (40%) had recanalized. Two patients (one from each group) had self-limited right upper quadrant pain after the procedure, and one patient in the coil embolization group required cholecystectomy.ConclusionProximal cystic artery embolization is safe and feasible and may be performed during liver-directed embolotherapy to minimize the exposure of the gallbladder to particulate, chemoembolic, or radioembolic agents

Inverse correlation between PDGFC expression and lymphocyte infiltration in human papillary thyroid carcinomas

<p>Abstract</p> <p>Background</p> <p>Members of the PDGF family have been suggested as potential biomarkers for papillary thyroid carcinomas (PTC). However, it is known that both expression and stimulatory effect of PDGF ligands can be affected by inflammatory cytokines. We have performed a microarray study in a collection of PTCs, of which about half the biopsies contained tumour-infiltrating lymphocytes or thyroiditis. To investigate the expression level of PDGF ligands and receptors in PTC we measured the relative mRNA expression of all members of the PDGF family by qRT-PCR in 10 classical PTC, eight clinically aggressive PTC, and five non-neoplastic thyroid specimens, and integrated qRT-PCR data with microarray data to enable us to link PDGF-associated gene expression profiles into networks based on recognized interactions. Finally, we investigated potential influence on PDGF mRNA levels by the presence of tumour-infiltrating lymphocytes.</p> <p>Methods</p> <p>qRT-PCR was performed on <it>PDGFA</it>, <it>PDGFB</it>, <it>PDGFC</it>, <it>PDGFD</it>, <it>PDGFRA PDGFRB </it>and a selection of lymphocyte specific mRNA transcripts. Semiquantitative assessment of tumour-infiltrating lymphocytes was performed on the adjacent part of the biopsy used for RNA extraction for all biopsies, while direct quantitation by qRT-PCR of lymphocyte-specific mRNA transcripts were performed on RNA also subjected to expression analysis. Relative expression values of PDGF family members were combined with a cDNA microarray dataset and analyzed based on clinical findings and PDGF expression patterns. Ingenuity Pathway Analysis (IPA) was used to elucidate potential molecular interactions and networks.</p> <p>Results</p> <p>PDGF family members were differentially regulated at the mRNA level in PTC as compared to normal thyroid specimens. Expression of <it>PDGFA </it>(p = 0.003), <it>PDGFB </it>(p = 0.01) and <it>PDGFC </it>(p = 0.006) were significantly up-regulated in PTCs compared to non-neoplastic thyroid tissue. In addition, expression of <it>PDGFC </it>was significantly up-regulated in classical PTCs as compared to clinically aggressive PTCs (p = 0.006), and <it>PDGFRB </it>were significantly up-regulated in clinically aggressive PTCs (p = 0.01) as compared to non-neoplastic tissue. Semiquantitative assessment of lymphocytes correlated well with quantitation of lymphocyte-specific gene expression. Further more, by combining TaqMan and microarray data we found a strong inverse correlation between <it>PDGFC </it>expression and the expression of lymphocyte specific mRNAs.</p> <p>Conclusion</p> <p>At the mRNA level, several members of the PDGF family are differentially expressed in PTCs as compared to normal thyroid tissue. Of these, only the <it>PDGFC </it>mRNA expression level initially seemed to distinguish classical PTCs from the more aggressive PTCs. However, further investigation showed that <it>PDGFC </it>expression level correlated inversely to the expression of several lymphocyte specific genes, and to the presence of lymphocytes in the biopsies. Thus, we find that <it>PDGFC </it>mRNA expression were down-regulated in biopsies containing infiltrated lymphocytes or thyroiditis. No other PDGF family member could be linked to lymphocyte specific gene expression in our collection of PTCs biopsies.</p

Measurement of w-InN/h-BN Heterojunction Band Offsets by X-Ray Photoemission Spectroscopy

X-ray photoelectron spectroscopy has been used to measure the valence band offset (VBO) of the w-InN/h-BN heterojunction. We find that it is a type-II heterojunction with the VBO being −0.30 ± 0.09 eV and the corresponding conduction band offset (CBO) being 4.99 ± 0.09 eV. The accurate determination of VBO and CBO is important for designing the w-InN/h-BN-based electronic devices

MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase–PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC

Reconstruction and control of a time-dependent two-electron wave packet

The concerted motion of two or more bound electrons governs atomic1 and molecular2,3 non-equilibrium processes including chemical reactions, and hence there is much interest in developing a detailed understanding of such electron dynamics in the quantum regime. However, there is no exact solution for the quantumthree-body problem, and as a result even the minimal system of two active electrons and a nucleus is analytically intractable4. This makes experimental measurements of the dynamics of two bound and correlated electrons, as found in the helium atom, an attractive prospect.However, although the motion of single active electrons and holes has been observed with attosecond time resolution5-7, comparable experiments on two-electron motion have so far remained out of reach. Here we showthat a correlated two-electron wave packet can be reconstructed froma 1.2-femtosecondquantumbeatamong low-lying doubly excited states in helium.The beat appears in attosecond transient-absorption spectra5,7-9 measured with unprecedentedly high spectral resolution and in the presence of an intensity-tunable visible laser field.Wetune the coupling10-12 between the two low-lying quantum states by adjusting the visible laser intensity, and use the Fano resonance as a phase-sensitive quantum interferometer13 to achieve coherent control of the two correlated electrons. Given the excellent agreement with large-scalequantum-mechanical calculations for thehelium atom, we anticipate thatmultidimensional spectroscopy experiments of the type we report here will provide benchmark data for testing fundamental few-body quantumdynamics theory in more complex systems. Theymight also provide a route to the site-specificmeasurement and control of metastable electronic transition states that are at the heart of fundamental chemical reactionsWe thank E. Lindroth for calculating the dipole moment (2p2|r|sp2,3+), and also A. Voitkiv, Z.-H. Loh, and R. Moshammer for helpful discussions. We acknowledge financial support by the Max-Planck Research Group Program of the Max-Planck Gesellschaft (MPG) and the European COST Action CM1204 XLIC. L. A. and F. M. acknowledge computer time from the CCC-UAM and Mare Nostrum supercomputer centers and financial support by the European Research Council under the ERC Advanced Grant no. 290853 XCHEM, the Ministerio de Economía y Competitividad projects FIS2010-15127, FIS2013-42002-R and ERA-Chemistry PIM2010EEC-00751, and the European grant MC-ITN CORIN

A Novel and Critical Role for Oct4 as a Regulator of the Maternal-Embryonic Transition

Compared to the emerging embryonic stem cell (ESC) gene network, little is known about the dynamic gene network that directs reprogramming in the early embryo. We hypothesized that Oct4, an ESC pluripotency regulator that is also highly expressed at the 1- to 2-cell stages in embryos, may be a critical regulator of the earliest gene network in the embryo.Using antisense morpholino oligonucleotide (MO)-mediated gene knockdown, we show that Oct4 is required for development prior to the blastocyst stage. Specifically, Oct4 has a novel and critical role in regulating genes that encode transcriptional and post-transcriptional regulators as early as the 2-cell stage. Our data suggest that the key function of Oct4 may be to switch the developmental program from one that is predominantly regulated by post-transcriptional control to one that depends on the transcriptional network. Further, we propose to rank candidate genes quantitatively based on the inter-embryo variation in their differential expression in response to Oct4 knockdown. Of over 30 genes analyzed according to this proposed paradigm, Rest and Mta2, both of which have established pluripotency functions in ESCs, were found to be the most tightly regulated by Oct4 at the 2-cell stage.We show that the Oct4-regulated gene set at the 1- to 2-cell stages of early embryo development is large and distinct from its established network in ESCs. Further, our experimental approach can be applied to dissect the gene regulatory network of Oct4 and other pluripotency regulators to deconstruct the dynamic developmental program in the early embryo

Disrupting the LINC complex by AAV mediated gene transduction prevents progression of Lamin induced cardiomyopathy

Data availability: The data supporting the conclusions of this paper are provided in the article and the Supplementary Information. Any remaining raw data will be available from the corresponding author upon reasonable request. Source Data are provided with this paper.Supplementary information is available online at https://www.nature.com/articles/s41467-021-24849-4#Sec23 .Source data are available online at https://www.nature.com/articles/s41467-021-24849-4#Sec24 .Mutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3–4 weeks after inducing the mutation. When the same Lmna mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year. Disruption of SUN1’s function is also accomplished by transducing and expressing a dominant-negative SUN1 miniprotein in Lmna deficient cardiomyocytes, using the cardiotrophic Adeno Associated Viral Vector 9. The SUN1 miniprotein disrupts binding between the endogenous LINC complex SUN and KASH domains, displacing the cardiomyocyte KASH complexes from the nuclear periphery, resulting in at least a fivefold extension in lifespan. Cardiomyocyte-specific expression of the SUN1 miniprotein prevents cardiomyopathy progression, potentially avoiding the necessity of developing a specific therapeutic tailored to treating each different LMNA cardiomyopathy-inducing mutation of which there are more than 450.This research was funded in part by the Singapore Biomedical Research Council Translational Clinical Research grant NMRC/TCR/006-NUHS/2013 to C.L.S. and R.S.Y.F., and the Singapore Agency for Science, Technology, and Research (A*STAR) to C.L.S