Proposal to distinguish HER2-low from HER2-normal breast cancer by in situ hybridisation.

Aims: 'HER2-low' breast cancer is an emerging issue as the clinical trials for anti-HER2 antibody-drug conjugates (trastuzumab deruxtecan) are making progress. A reliable method to identify HER2-low cancers is needed. This study aimed to evaluate immunohistochemistry (IHC) and in situ hybridisation (ISH) in detecting HER2-low status.

Upregulation of USP22 and ABCC1 during Sorafenib Treatment of Hepatocellular Carcinoma Contribute to Development of Resistance.

Sorafenib is a small molecule that blocks tumor proliferation by targeting the activity of multi-kinases for the treatment of advanced hepatocellular carcinoma (HCC). Increasing sorafenib resistance following long-term treatment is frequently encountered. Mechanisms underlying sorafenib resistance remain not completely clear.

Pcsk9 Deletion Promotes Murine Nonalcoholic Steatohepatitis and Hepatic Carcinogenesis: Role of Cholesterol.

Proprotein convertase subtilisin/kexin type 9 (Pcsk9) binds to hepatic low-density lipoprotein receptor (LDLR) and induces its internalization and degradation. Pcsk9 inhibition increases LDLR expression by hepatocytes, which causes increased uptake of circulating LDL, thereby reducing plasma LDL-cholesterol. However, by increasing the uptake of LDL by the liver, Pcsk9 inhibition increases the exposure of the liver to cholesterol, which may result in higher risk of steatohepatitis and ever carcinogenesis.

Non-alcoholic fatty liver disease: A review with clinical and pathological correlation.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in North America and Europe, with increasing prevalence in other regions of the world. Its spectrum encompass steatosis, non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. It is considered as the manifestation of metabolic syndrome in liver, and its development and progression is influenced by complex interaction of environmental and genetic factors.

Immune-related adverse reactions in the hepatobiliary system: second-generation check-point inhibitors highlight diverse histological changes.

Aims: Immune check-point inhibitors are known to cause immune-mediated adverse liver injury, but our knowledge is mainly based on cases treated with ipilimumab or nivolumab.

Methods And Results: Clinicopathological features of 10 patients with hepatobiliary adverse reactions caused by second-generation drugs, pembrolizumab (n = 6) and atezolizumab (n = 4), were reviewed. Liver dysfunction developed during a median period of 3.

Loss of BCAT1 Expression is a Sensitive Marker for IDH-Mutant Diffuse Glioma.

Background: IDH mutation is an important prognostic factor of diffuse astrocytomas. Although the majority of IDH mutations could be identified by immunohistochemical (IHC) stain for R132H-mutant IDH1, DNA sequencing would be required for IHC negative cases to determine their IDH mutation status. This approach is not cost-effective for tumors with low IDH mutation rates.

Upregulation of miR-125b, miR-181d, and miR-221 Predicts Poor Prognosis in MGMT Promoter-Unmethylated Glioblastoma Patients.

Objectives: To evaluate the prognostic values of microRNAs (miRNAs) in glioblastoma, and to see if there is an association between miRNAs and MGMT promoter methylation status.

Methods: We collected paraffin blocks from resection specimens from 114 glioblastoma patients who had received temozolomide treatment and radiotherapy. Real-time quantitative PCR was performed to determine the expression levels of five miRNAs.

Advancing a High Throughput Glycotope-centric Glycomics Workflow Based on nanoLC-MS-product Dependent-MS Analysis of Permethylated Glycans.

The intrinsic nature of glycosylation, namely nontemplate encoded, stepwise elongation and termination with a diverse range of isomeric glyco-epitopes (glycotopes), translates into ambiguity in most cases of mass spectrometry (MS)-based glycomic mapping. It is arguable that whether one needs to delineate every single glycomic entity, which may be counterproductive. Instead, one should focus on identifying as many structural features as possible that would collectively define the glycomic characteristics of a cell or tissue, and how these may change in response to self-programmed development, immuno-activation, and malignant transformation.

Adjust cut-off values of immunohistochemistry models to predict risk of distant recurrence in invasive breast carcinoma patients.

Background: Multigene assays are recommended for hormone receptor-positive invasive breast carcinoma to determine the risk of recurrence, but they are highly expensive. We investigated the prognostic values of immunohistochemistry (IHC)-based prognostic models as an alternative to multigene assays.

Methods: The risk categories estimated by the IHC-based prognostic models were correlated to those estimated by the multigene assays in 71 cases and the follow-up results in 642 consecutive cases of HER2- luminal-type early breast cancer.

Switching of the core structures of glycosphingolipids from globo- and lacto- to ganglio-series upon human embryonic stem cell differentiation.

A systematic survey of expression profiles of glycosphingolipids (GSLs) in two hESC lines and their differentiated embryoid body (EB) outgrowth with three germ layers was carried out using immunofluorescence, flow cytometry, and MALDI-MS and MS/MS analyses. In addition to the well-known hESC-specific markers stage-specific embryonic antigen 3 (SSEA-3) and SSEA-4, we identified several globosides and lacto-series GSLs, previously unrevealed in hESCs, including Gb(4)Cer, Lc(4)Cer, fucosyl Lc(4)Cer, Globo H, and disialyl Gb(5)Cer. During hESC differentiation into EBs, MS analysis revealed a clear-cut switch in the core structures of GSLs from globo- and lacto- to ganglio-series, which was not as evident by immunostaining with antibodies against SSEA-3 and SSEA-4, owing to their cross-reactivities with various glycosphingolipids.

Enhanced expression of beta 3-galactosyltransferase 5 activity is sufficient to induce in vivo synthesis of extended type 1 chains on lactosylceramides of selected human colonic carcinoma cell lines.

In general, an elevated expression of beta 3-galactosyltransferase (beta 3GalT) activity contributed by beta 3GalT5 correlates well with increased biosynthesis and expression of type 1 chain (Gal beta 1-3GlcNAc beta 1-) derivatives such as Lewis A and sialyl Lewis A, which are mostly recognized as terminal epitopes and not further extended. Most known beta 3-N-acetylglucosaminyltransferases show a higher activity toward extending type 2 chain (Gal beta 1-4GlcNAc beta 1-), and an over-expression of beta 3GalT5 could suppress the formation of the type 2 chain poly-N-acetyllactosaminoglycans. The potential of extending instead the predominant type 1 chain termini synthesized under such circumstances was, however, not investigated, partly due to technical difficulty in unambiguous identification of extended type 1 chains.