Vogt-Koyanagi-Harada-Like Uveitis Secondary to Pembrolizumab in Metastatic Gastric Cancer: A Case Report and Review of the Literature.

Introduction: Vogt-Koyanagi-Harada (VKH) disease is a multisystem syndrome characterized by uveitis and exudative retinal detachments in the absence of ocular trauma or surgery. Neurological and cutaneous manifestations can also occur. Prior case reports have associated immune checkpoint inhibitors with a VKH-like disease.

International Multicenter Retrospective Study From the Ultra-rare Sarcoma Working Group on Low-grade Fibromyxoid Sarcoma, Sclerosing Epithelioid Fibrosarcoma, and Hybrid Forms: Outcome of Primary Localized Disease.

The aim of the study was to report the outcome of primary localized low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid LGFMS/SEF (H-LGFMS/SEF). Patients with primary localized LGFMS, SEF, or H-LGFMS/SEF, surgically treated with curative intent from January 2000 to September 2022, were enrolled from 14 countries and 27 institutions. Pathologic inclusion criteria were predefined by expert pathologists.

Utility of Clinical Next Generation Sequencing Tests in KIT/PDGFRA/SDH Wild-Type Gastrointestinal Stromal Tumors.

The vast majority of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in , , or components of the succinate dehydrogenase (SDH) complex (, , , and genes). A small fraction of GISTs lack alterations in , , and . We aimed to further characterize the clinical and genomic characteristics of these so-called "triple-negative" GISTs.

Pleural fluid characteristics of patients with COVID-19 infection.

Introduction: Pleural effusions are known to occur in many cases of COVID-19. Data on typical characteristics of COVID-19-associated pleural effusions are limited. The goal of this project was to characterize the pleural fluid from patients with COVID-19.

Clinical Outcomes Among Immunotherapy-Treated Patients With Primary Cardiac Soft Tissue Sarcomas: A Multicenter Retrospective Study.

Background: Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes.

Objectives: The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs).

Methods: A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022.

The Future of Targeted Therapy for Leiomyosarcoma.

Leiomyosarcoma (LMS) is an aggressive subtype of soft tissue sarcoma that arises from smooth muscle cells, most commonly in the uterus and retroperitoneum. LMS is a heterogeneous disease with diverse clinical and molecular characteristics that have yet to be fully understood. Molecular profiling has uncovered possible targets amenable to treatment, though this has yet to translate into approved targeted therapies in LMS.

Clinico-Genomic Profiling of Conventional and Dedifferentiated Chondrosarcomas Reveals TP53 Mutation to Be Associated with Worse Outcomes.

Purpose: Chondrosarcomas are the most common primary bone tumor in adults. Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are prevalent. We aimed to assess the clinico-genomic properties of IDH mutant versus IDH wild-type (WT) chondrosarcomas as well as alterations in other genes.

The Landscape of Alterations from 1407 Ultra-Rare Sarcomas from the AACR GENIE Database: Clinical Implications.

Purpose: Ultra-rare sarcomas (URS) comprise a group of orphan diseases with an incidence of ≤1/1,000,000 people per year. We aimed to assess clinically actionable genomic alterations in URS.

Experimental Design: Data were extracted from the GENIE database using cBioPortal.

Misaligned Chromosomes are a Major Source of Chromosomal Instability in Breast Cancer.

Unlabelled: Chromosomal instability (CIN), the persistent reshuffling of chromosomes during mitosis, is a hallmark of human cancers that contributes to tumor heterogeneity and has been implicated in driving metastasis and altering responses to therapy. Though multiple mechanisms can produce CIN, lagging chromosomes generated from abnormal merotelic attachments are the major cause of CIN in a variety of cell lines, and are expected to predominate in cancer. Here, we quantify CIN in breast cancer using a tumor microarray, matched primary and metastatic samples, and patient-derived organoids from primary breast cancer.

PLK4 is upregulated in prostate cancer and its inhibition reduces centrosome amplification and causes senescence.

Background: Identification of novel molecular target(s) is important for designing newer mechanistically driven approaches for the treatment of prostate cancer (PCa), which is one of the main causes of morbidity and mortality in men. In this study, we determined the role of polo-like kinase 4 (PLK4), which regulates centriole duplication and centrosome amplification (CA), in PCa.

Materials And Methods: Employing human PCa tissue microarrays, we assessed the prevalence of CA, correlated with Gleason score, and estimated major causes of CA in PCa (cell doubling vs.

Undifferentiated and Unresectable Sarcoma With NTRK3-Fusion in a Pediatric Patient Treated With Larotrectinib and Proton Beam Radiotherapy.

A 6-year-old female presenting with an abdominal mass was found to have an unresectable undifferentiated sarcoma. The tumor did not respond to multiagent chemotherapy. However, molecular testing identified an NTRK3-fusion, and treatment was changed to larotrectinib monotherapy.

Centriole and Golgi microtubule nucleation are dispensable for the migration of human neutrophil-like cells.

Neutrophils migrate in response to chemoattractants to mediate host defense. Chemoattractants drive rapid intracellular cytoskeletal rearrangements including the radiation of microtubules from the microtubule-organizing center (MTOC) toward the rear of polarized neutrophils. Microtubules regulate neutrophil polarity and motility, but little is known about the specific role of MTOCs.

Optimization of oxidative stress for mesenchymal stromal/stem cell engraftment, function and longevity.

Mesenchymal stromal/stem cells (MSCs) are multipotent cells that possess great potential as a cellular therapeutic based on their ability to differentiate to different lineages and to modulate immune responses. However, their potential is limited by their low tissue abundance, and thus the need for robust ex vivo expansion prior to their application. This creates its own issues, namely replicative senescence, which could lead to reduced MSC functionality and negatively impact their engraftment.

High nuclear TPX2 expression correlates with TP53 mutation and poor clinical behavior in a large breast cancer cohort, but is not an independent predictor of chromosomal instability.

Background: Targeting Protein for Xenopus Kinesin Like Protein 2 (TPX2) is a microtubule associated protein that functions in mitotic spindle assembly. TPX2 also localizes to the nucleus where it functions in DNA damage repair during S-phase. We and others have previously shown that TPX2 RNA levels are strongly associated with chromosomal instability (CIN) in breast and other cancers, and TPX2 RNA levels have been demonstrated to correlate with aggressive behavior and poor clinical outcome across a range of solid malignancies, including breast cancer.

Analysis of the "centrosome-ome" identifies MCPH1 deletion as a cause of centrosome amplification in human cancer.

The centrosome is the microtubule organizing center of human cells and facilitates a myriad of cellular functions including organization of the mitotic spindle to ensure faithful chromosome segregation during mitosis, cell polarization and migration, and primary cilia formation. A numerical increase in centrosomes, or centrosome amplification (CA), is common in cancer and correlates with more aggressive clinical features and worse patient outcomes. However, the causes of CA in human cancer are unclear.

MRSA Septicemia With Septic Arthritis and Prostatic, Intraretinal, Periapical, and Lung Abscesses.

Introduction: Methicillin-resistant staphylococcus aureus (MRSA) bacteremia is a life-threatening illness and a major global health care problem. It can cause metastatic and complicated infections.

Case Presentation: A 58-year-old man with uncontrolled type 2 diabetes mellitus presented with altered mental status after a fall.

Centrosome amplification is a frequent event in circulating tumor cells from subjects with metastatic breast cancer.

Centrosome amplification (CA) is a common phenomenon in cancer, promotes genomic stability and cancer evolution, and has been reported to promote metastasis. CA promotes a stochastic gain/loss of chromosomes during cell division, known as chromosomal instability (CIN). However, it is unclear whether CA is present in circulating tumor cells (CTCs), the seeds for metastasis.

Survey of Radon Testing and Mitigation by Wisconsin Residents, Landlords, and School Districts.

Introduction: Radon is the second-leading cause of lung cancer in the United States, the leading cause of lung cancer in nonsmokers, and is estimated to cause 21,000 deaths every year. Radon is especially prevalent in the upper Midwest. This study aimed to assess radon testing and mitigation practices among residential homeowners, landlords, and school districts in Wisconsin.

Association of Immune Thrombocytopenia and T-Lymphoblastic Lymphoma in a Pediatric Patient.

Immune thrombocytopenia (ITP) is characterized by isolated thrombocytopenia of unclear etiology. We present a unique case of an 8-year-old girl with chronic ITP who was subsequently diagnosed with T-lymphoblastic lymphoma at age 11. The clinical course was complicated by the occurrence of nonepileptiform events with bizarre behavior changes following the administration of nelarabine and intrathecal and high-dose systemic methotrexate.

Centrosome Amplification in Cancer Disrupts Autophagy and Sensitizes to Autophagy Inhibition.

Centrosome amplification (CA), or a numerical increase in centrosomes, is common in human cancers, particularly those with high-risk features. We have discovered that cells with CA have an increased burden of autophagy, a catabolic process whereby autophagosomes engulf damaged organelles and proteins and deliver these contents to the lysosome for degradation and subsequent recycling. Cells with CA demonstrate an accumulation of autophagosomes.

Polo-like kinase 4 maintains centriolar satellite integrity by phosphorylation of centrosomal protein 131 (CEP131).

The centrosome, consisting of two centrioles surrounded by a dense network of proteins, is the microtubule-organizing center of animal cells. Polo-like kinase 4 (PLK4) is a Ser/Thr protein kinase and the master regulator of centriole duplication, but it may play additional roles in centrosome function. To identify additional proteins regulated by PLK4, we generated an RPE-1 human cell line with a genetically engineered "analog-sensitive" PLK4, which genetically encodes chemical sensitivity to competitive inhibition via a bulky ATP analog.