Sensitizing cholangiocarcinoma to chemotherapy by inhibition of the drug-export pump MRP3.

Aims: Drug export through ABC proteins hinders cancer response to chemotherapy. Here, we have evaluated the relevance of MRP3 (ABCC3) in cholangiocarcinoma (CCA) as a potential target to overcome drug resistance.

Methods: Gene expression was analyzed in silico using the TCGA-CHOL database and experimentally (mRNA and protein) in resected CCA tumors.

Protonation of Dppbz- and Binap-Ligated Rhodathiaboranes Yielding Hydron, Hydride, and Hydrogen Exchange.

The reaction of the 11-vertex rhodathiaborane [8,8,8-(H)(PPh)-3-(NCH)--7,8-RhSBH] () with 1,2-bis(diphenylphosphine)benzene (dppbz) and ()-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (binap) affords [1,1-(η-dppbz)-3-(NCH)--1,2-RhSBH] () and [1,1-(η-binap)-3-(NCH)--1,2-RhSBH] (). These 11-vertex -rhodathiaborane chelates result from PPh ligand substitution at the rhodium center and a -to- structural cluster transformation driven by H loss. Treating compounds and with triflic acid (TfOH) leads to the formation of cationic clusters and .

The Search for Risk, Diagnostic, and Prognostic Biomarkers of Cholangiocarcinoma and Their Biological and Clinicopathologic Significance.

Cholangiocarcinomas (CCAs) are a heterogeneous group of malignant tumors that originate from the biliary tract. They are usually diagnosed in advanced stages, leading to a dismal prognosis for affected patients. As CCA often arises as a sporadic cancer in individuals lacking specific risk factors or with heterogeneous backgrounds, and there are no defined high-risk groups, the implementation of effective surveillance programs for CCA is problematic.

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease.

Background: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy.

Methods: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry.

Strategies to enhance the response of liver cancer to pharmacological treatments.

In contrast to other types of cancers, there is no available efficient pharmacological treatment to improve the outcomes of patients suffering from major primary liver cancers, i.e., hepatocellular carcinoma and cholangiocarcinoma.

Impact of liver diseases and pharmacological interactions on the transportome involved in hepatic drug disposition.

The liver plays a pivotal role in drug disposition owing to the expression of transporters accounting for the uptake at the sinusoidal membrane and the efflux across the basolateral and canalicular membranes of hepatocytes of many different compounds. Moreover, intracellular mechanisms of phases I and II biotransformation generate, in general, inactive compounds that are more polar and easier to eliminate into bile or refluxed back toward the blood for their elimination by the kidneys, which becomes crucial when the biliary route is hampered. The set of transporters expressed at a given time, i.

Reamer irrigator aspirator (RIA) reduces risk of fat embolism in bilateral pediatric femur shaft fractures: a case report.

A 14-year-old male patient was successfully treated with the reamer irrigator aspirator for femur intramedullary rod preparation after sustaining right and left closed femur fractures because of an all-terrain vehicle accident. In patients already categorized as high risk for fat embolism syndrome, such as those with bilateral femur fractures, reaming both femora greatly increases the likelihood of this complication. The reamer irrigator aspirator provides an effective tool that potentially mitigates the risk of fat embolism syndrome in pediatric patients with this type of orthopedic trauma.

A cluster differences unfolding method for large datasets of preference ratings on an interval scale: Minimizing the mean squared centred residuals.

Clustering and spatial representation methods are often used in combination, to analyse preference ratings when a large number of individuals and/or object is involved. When analysed under an unfolding model, row-conditional linear transformations are usually most appropriate when the goal is to determine clusters of individuals with similar preferences. However, a significant problem with transformations that include both slope and intercept is the occurrence of degenerate solutions.

An HTLV-1 envelope mRNA vaccine is immunogenic and protective in New Zealand rabbits.

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus responsible for adult T-cell leukemia/lymphoma, a severe and fatal CD4+ T-cell malignancy. Additionally, HTLV-1 can lead to a chronic progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis. Unfortunately, the prognosis for HTLV-1-related diseases is generally poor, and effective treatment options are limited.

Sensitization of cholangiocarcinoma cells to chemotherapy through BCRP inhibition with β-caryophyllene oxide.

Cholangiocarcinomas (CCAs) are cancers originated in the biliary tree, which are characterized by their high mortality and marked chemoresistance, partly due to the activity of ATP-binding cassette (ABC) export pumps, whose inhibition has been proposed as a strategy for enhancing the response to chemotherapy. We have previously shown that β-caryophyllene oxide (CRYO) acts as a chemosensitizer in hepatocellular carcinoma by inhibiting ABCB1, MRP1, and MRP2. Here, we have evaluated the usefulness of CRYO in inhibiting BCRP and improving the response of CCA to antitumor drugs.

TGFβ-induced circLTBP2 predicts a poor prognosis in intrahepatic cholangiocarcinoma and mediates gemcitabine resistance by sponging miR-338-3p.

Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide with an increasing incidence and limited therapeutic options. Therefore, there is an urgent need to open the field to new concepts for identifying clinically relevant therapeutic targets and biomarkers. Here, we explored the role and the clinical relevance of circular RNA (circRNA) circLTBP2 in iCCA.

Prevalence and Impact of Feeding-Related Events on Hospital Stay in Preterm and Term Newborns.

Background: Nursing assessment of milk flow regulation and associated apnea, bradycardia, and desaturation (ABD events) contribute to considerations for the discharge of newborns from the acute care setting. Research regarding infant feeding-related (FR) events (sucking and swallowing difficulties) and ABD events in moderate to late-preterm and full-term infants is lacking.

Purpose: This study observes the impact of FR and ABD events during feeding on hospital length of stay (LOS) and healthcare utilization (cost) in moderate-to-late preterm newborns, as well as full-term infants.

Evaluation of potential targets to enhance the sensitivity of cholangiocarcinoma cells to anticancer drugs.

Background: Cholangiocarcinoma (CCA) is a highly lethal cancer originated in the biliary tree. Available treatments for CCA are scarcely effective, partly due to mechanisms of chemoresistance, such as aberrant activation of Wnt/β-catenin pathway and dysfunctional p53.

Aim: To evaluate the impact of enhancing the expression of negative regulators of the Wnt/β-catenin pathway (AXIN1, AXIN2, and GSK3B) and the tumor suppressor gene TP53.

The Synthesis, Characterization, and Fluxional Behavior of a Hydridorhodatetraborane.

The octahydridotriborate anion plays a crucial role in the field of polyhedral boron chemistry, facilitating the synthesis of higher boranes and the preparation of diverse transition metal complexes. Among the stable forms of this anion, CsBH (or (n-CH)N)[BH] have been identified. These salts serve as valuable precursors for the synthesis of metallaboranes, wherein the triborate anion acts as a ligand coordinating to the metal center.

Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors.

Impaired function of organic cation transporter 1 (OCT1) in hepatocellular carcinoma (HCC) has been associated with unsatisfactory response to sorafenib. However, some patients lacking OCT1 at the plasma membrane (PM) of HCC cells still respond to sorafenib, suggesting that another transporter may contribute to take up this drug. The aim of this study was to investigate whether OCT3 could contribute to the uptake of sorafenib and other tyrosine kinase inhibitors (TKIs) and whether OCT3 determination can predict HCC response to sorafenib.

Simple Route to [PSH][BH] and a Contemporary Study of Its Solid-State Dynamic Behavior.

The 1,8-bis(dimethylamino)naphthalenium ([PSH]) decaborane salt, [PSH][BH], has been found to react in ethanol to form [PSH][BH] (), affording a simple route to the synthesis of the -nonaborate anion. This new polyhedral salt is characterized by NMR spectroscopy and X-ray diffraction. The measurement of diffusion coefficients by NMR methods demonstrates that the [PSH] cation and the [BH] anion form ion pairs in a non-coordinating solvent such as CHCl, whereas in CDCN the formation of ion pairs was not observed.

Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis.

Background: Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential in order to identify those patients who may benefit most from this novel treatment option. Here, we propose a systematic literature review and a meta-analysis of PD-1, PD-L1, and other immune-related biomarker expression levels in patients with BTC.

Relevance of the organic anion transporting polypeptide 1B3 (OATP1B3) in the personalized pharmacological treatment of hepatocellular carcinoma.

Although pharmacological treatment is the best option for most patients with advanced hepatocellular carcinoma (HCC), its success is very limited, partly due to reduced uptake and enhanced efflux of antitumor drugs. Here we have explored the usefulness of vectorizing drugs towards the organic anion transporting polypeptide 1B3 (OATP1B3) to enhance their efficacy against HCC cells. In silico studies (RNA-Seq data, 11 cohorts) and immunohistochemistry analyses revealed a marked interindividual variability, together with general downregulation but still expression of OATP1B3 in the plasma membrane of HCC cells.

Design of Ti64/Ta Hybrid Materials by Powder Metallurgy Mimicking Bone Structure.

This work reports on the fabrication of a novel two-layer material composed of a porous tantalum core and a dense Ti6Al4V (Ti64) shell by powder metallurgy. The porous core was obtained by mixing Ta particles and salt space-holders to create large pores, the green compact was obtained by pressing. The sintering behavior of the two-layer sample was studied by dilatometry.

Role of Intracellular Drug Disposition in the Response of Acute Myeloid Leukemia to Cytarabine and Idarubicin Induction Chemotherapy.

Despite its often low efficacy and high toxicity, the standard treatment for acute myeloid leukemia (AML) is induction chemotherapy with cytarabine and idarubicin. Here, we have investigated the role of transporters and drug-metabolizing enzymes in this poor outcome. The expression levels (RT-qPCR) of potentially responsible genes in blasts collected at diagnosis were related to the subsequent response to two-cycle induction chemotherapy.

Impact of Aberrant β-Catenin Pathway on Cholangiocarcinoma Heterogeneity.

The poor prognosis of most cases of advanced cholangiocarcinoma (CCA) constitutes a severe problem in modern oncology, which is aggravated by the fact that the incidence of this liver cancer is increasing worldwide and is often diagnosed late, when surgical removal is not feasible. The difficulty of dealing with this deadly tumor is augmented by the heterogeneity of CCA subtypes and the complexity of mechanisms involved in enhanced proliferation, apoptosis avoidance, chemoresistance, invasiveness, and metastasis that characterize CCA. Among the regulatory processes implicated in developing these malignant traits, the Wnt/β-catenin pathway plays a pivotal role.