Prognosis and tumor microenvironment in pseudohypoxic pheochromocytoma/paraganglioma.

Pheochromocytoma and paraganglioma (PPGL) are rare tumors that occur in the adrenal medulla and extra-adrenal tissues, respectively. The prognosis and tumor microenvironment (TME) of pseudohypoxic PPGL as a major entity have not been fully described. Based on the clinical database of 65 patients with PPGL, we assessed the morphological features as well as the immunohistochemistry of pseudohypoxia-related proteins (SDHB and CAIX) and TME-related immune cell markers.

Spatiotemporal functions of leukemia inhibitory factor in embryo attachment and implantation chamber formation.

Embryo implantation is crucial for successful pregnancy, requiring appropriate uterine responses to implantation-competent blastocysts. Molecular communication at the maternal-fetal junction governs this process. Leukemia inhibitory factor (Lif) plays a pivotal role in implantation across species.

Mathematical model of structural changes in nuclear speckle.

Nuclear speckles are nuclear bodies consisting of populations of small and irregularly shaped droplet-like molecular condensates that contain various splicing factors. Recent experiments have revealed the following structural features of nuclear speckles: (I) Each molecular condensate contains SON and SRRM2 proteins, and 1 non-coding RNA surrounds these condensates; (II) During normal interphase of the cell cycle in multicellular organisms, these condensates are broadly distributed throughout the nucleus. In contrast, when cell transcription is suppressed, the condensates fuse and form strongly condensed spherical droplets; (III) SON is dispersed spatially in knocked-down cells and is dispersed in SON knocked-down cells because of the collapse of the nuclear speckles.

Methylated histones on mitotic chromosomes promote topoisomerase IIα function for high fidelity chromosome segregation.

DNA Topoisomerase IIα (TopoIIα) decatenates sister chromatids, allowing their segregation in mitosis. Without the TopoIIα Strand Passage Reaction (SPR), chromosome bridges and ultra-fine DNA bridges (UFBs) arise in anaphase. The TopoIIα C-terminal domain is dispensable for the SPR but essential for mitotic functions .

Effectiveness and tasks of breast MRI surveillance for high-risk women with cancer susceptibility genes other than BRCA1/2: a single institution study.

Background: In Japan, with the introduction of multigene panel testing, there is an urgent need to build a new medical system for hereditary breast cancer patients that covers pathogenic variants other than BRCA1/2. The aim of this study was to reveal the current status of breast MRI surveillance for high-risk breast cancer susceptibility genes other than BRCA1/2 and the characteristics of detected breast cancer.

Methods: We retrospectively examined 42 breast MRI surveillance with contrast performed on patients with hereditary tumors other than BRCA1/2 pathogenic variants at our hospital from 2017 to 2021.

Exploring Predictive Risk Factors of Infusion Reactions with First Pertuzumab Administration in HER2-positive Breast Cancer Patients: A Single Institution Experience.

Introduction: Pertuzumab and trastuzumab are monoclonal antibodies used for treating HER2-positive breast cancer. These anti-HER2 antibodies may induce infusion reactions (IR), mainly upon first administration. We investigated factors predicting IR in the initial pertuzumab treatment for HER2-positive breast cancer.

Novel compound heterozygous mutations in UHRF1 are associated with atypical immunodeficiency, centromeric instability and facial anomalies syndrome with distinctive genome-wide DNA hypomethylation.

Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is in most cases caused by mutations in either DNA methyltransferase (DNMT)3B, zinc finger and BTB domain containing 24, cell division cycle associated 7 or helicase lymphoid-specific. However, the causative genes of a few ICF patients remain unknown. We, herein, identified ubiquitin-like with plant homeodomain and really interesting new gene finger domains 1 (UHRF1) as a novel causative gene of one such patient with atypical symptoms.

Clinical significance of the neutrophil-to-lymphocyte ratio in oligometastatic breast cancer.

Purpose: This study investigated the clinical impact of pretreatment neutrophil-to-lymphocyte ratio (NLR) on survival in patients with oligometastatic breast cancer.

Patients And Methods: We collected data from 397 patients who underwent primary breast surgery from 2004 to 2015 and developed recurrence during the follow-up. We reviewed the images and clinical information and defined OMD according to the European Society for Medical Oncology advanced breast cancer guidelines.

KRAS variant allele frequency, but not mutation positivity, associates with survival of patients with pancreatic cancer.

KRAS mutation is a major driver of pancreatic carcinogenesis and will likely be a therapeutic target. Due to lack of sensitive assays for clinical samples of pancreatic cancer with low cellularity, KRAS mutations and their prognostic association have not been fully examined in large populations. In a multi-institutional cohort of 1162 pancreatic cancer patients with formalin-fixed paraffin-embedded tumor samples, we undertook droplet digital PCR (ddPCR) for KRAS codons 12/13/61.

Ribosomal protein L5 facilitates rDNA-bundled condensate and nucleolar assembly.

The nucleolus is the site of ribosome assembly and formed through liquid-liquid phase separation. Multiple ribosomal DNA (rDNA) arrays are bundled in the nucleolus, but the underlying mechanism and significance are unknown. In the present study, we performed high-content screening followed by image profiling with the wndchrm machine learning algorithm.

Modeling population size independent tissue epigenomes by ChIL-seq with single thin sections.

Recent advances in genome-wide technologies have enabled analyses using small cell numbers of even single cells. However, obtaining tissue epigenomes with cell-type resolution from large organs and tissues still remains challenging, especially when the available material is limited. Here, we present a ChIL-based approach for analyzing the diverse cellular dynamics at the tissue level using high-depth epigenomic data.

Cryo-EM structure of the nucleosome core particle containing Giardia lamblia histones.

Giardia lamblia is a pathogenic unicellular eukaryotic parasite that causes giardiasis. Its genome encodes the canonical histones H2A, H2B, H3, and H4, which share low amino acid sequence identity with their human orthologues. We determined the structure of the G.

Quantitative assessment of HER2 gene amplification of breast cancer using droplet digital PCR.

We previously reported the usefulness of droplet digital polymerase chain reaction (ddPCR) for the assessment of Human epithelial growth factor receptor 2 (HER2) gene amplification in breast cancer using formalin-fixed and paraffin-embedded sections. In our previous study, we combined HER2/CEP17 ratio (HER2 gene signals to chromosome 17 signals) with ddPCR and tumor content ratio (TCR) of each sample and determined the HER2 status by adopting a two-dimensional chart. This "ddPCR-TCR method" showed a high concordance with conventional HER2 status.

Probing the tumorigenic potential of genetic interactions reconstituted in murine fallopian tube organoids.

Genetically engineered mice have been the gold standard in modeling tumor development. Recent studies have demonstrated that genetically engineered organoids can develop subcutaneous tumors in immunocompromised mice, at least for organs that prefer predominant driver mutations for tumorigenesis. To further substantiate this concept, the fallopian tube (FT), a major cell of origin of ovarian high-grade serous carcinoma (HGSC), which almost invariably carries TP53 mutations, was investigated for p53 inactivation-driven tumorigenesis.

Assessment of axillary node status by ultrasound after neoadjuvant chemotherapy in patients with clinically node-positive breast cancer according to breast cancer subtype.

The use of sentinel node biopsy (SNB) following neoadjuvant chemotherapy (NAC) for patients with cN1 breast cancer is controversial. Improvements of negative predictive value (NPV) by axillary ultrasound (AUS), which corresponds to the accurate prediction rate of node-negative status after NAC, would lead to decreased FNR of SNB following NAC. In this study, we retrospectively investigated the accurate prediction rate of NPV by AUS after NAC in patients with cytologically node-positive breast cancer treated between January 2012 and December 2016.

Myofibroblastoma of the breast showing rare palisaded morphology and uncommon desmin- and CD34-negative immunophenotype: A case report.

Myofibroblastoma is a rare benign mesenchymal tumor typically arising in the breast. We report a diagnostically challenging case of myofibroblastoma of the breast showing a rare palisaded morphology and an uncommon desmin- and CD34-negative immunophenotype. A 73-year-old man underwent an excision for an 8 mm-sized breast mass.

Chromatin structure-dependent histone incorporation revealed by a genome-wide deposition assay.

In eukaryotes, histone variant distribution within the genome is the key epigenetic feature. To understand how each histone variant is targeted to the genome, we developed a new method, the RhIP (econstituted istone complex ncorporation into chromatin of ermeabilized cell) assay, in which epitope-tagged histone complexes are introduced into permeabilized cells and incorporated into their chromatin. Using this method, we found that H3.

Metastatic ovarian cancer spreading into mammary ducts mimicking an in situ component of primary breast cancer: a case report.

Background: Accurate diagnosis of metastatic tumors in the breast is crucial because the therapeutic approach is essentially different from primary tumors. A key morphological feature of metastatic tumors is their lack of an in situ carcinoma component. Here, we present a unique case of metastatic ovarian carcinoma spreading into mammary ducts and mimicked an in situ component of primary carcinoma.

Transformation from adenocarcinoma to squamous cell lung carcinoma with MET amplification after lorlatinib resistance: A case report.

To date, several studies have described the mechanism of resistance to first- or second-generation anaplastic lymphoma kinase (ALK) inhibitors. Secondary ALK mutations, ALK gene amplification, and other bypass signal activations (i.e.

Evaluating the usefulness of breast strain elastography for intraductal lesions.

Purpose: Strain elastography for imaging lesion stiffness is being used as a diagnostic aid in the malignant/benign discrimination of breast diseases. While acquiring elastography in addition to B-mode images has been reported to help avoid performing unnecessary biopsies, intraductal lesions are difficult to discriminate whether they are malignant or benign using elastography. An objective evaluation of strain in lesions was performed in this study by measuring the elasticity index (E-index) and elasticity ratio (E-ratio) of lesions as semi-quantitative numerical indicators of the color distribution of strain.

Hepatocellular adenoma, approximately half and predominantly inflammatory subtype, in 38 Japanese patients with several differences in age, gender, and clinical background factors from Western populations.

Aim: Hepatocellular adenoma (HCA) has a lower prevalence in Japan than in Western countries and HCA subtypes have been reported for only a few Japanese patients. We analyzed HCA subtype data 38 patients from 23 hospitals in Japan in order to examine character and difference between Western countries.

Methods: To confirm HCA and to analyze subtypes, we performed immunohistochemical examinations.