Transcriptomics of acute myeloid leukaemia core bone marrow biopsies reveals distinct therapy response-specific osteo-mesenchymal profiles.

While the bone marrow (BM) microenvironment is significantly remodelled in acute myeloid leukaemia (AML), molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates rather than core biopsies that contain solid-phase BM stroma. We assessed the effect of anthracycline- and cytarabine-based induction chemotherapy on both haematopoietic and non-haematopoietic cells directly in core BM biopsies using RNA-seq and histological analysis. We compared matched human core BM biopsies at diagnosis and 2 weeks after cytarabine- and anthracycline-based induction therapy in responders (<5% blasts present after treatment) and non-responders (≥5% blasts present after treatment).

Stem cell phenotype predicts therapeutic response in glioblastomas with MGMT promoter methylation.

A growing body of evidence supports the presence of a population of cells in glioblastoma (GBM) with a stem cell-like phenotype which shares certain biological markers with adult neural stem cells, including expression of SOX2, CD133 (PROM1), and NES (nestin). This study was designed to determine the relationship between the expression of these stem cell markers and the clinical outcome in GBM patients. We quantified the intensity of expression of the proteins CD133 and SOX2 by immunohistochemistry (IHC) in a cohort of 86 patients with IDH-wildtype GBM, and evaluated patient outcomes using Kaplan-Meier and Cox proportional hazards analysis.

FOXO3 regulates a common genomic program in aging and glioblastoma stem cells.

Background: Glioblastoma (GBM) is an aggressive, age-associated malignant glioma that contains populations of cancer stem cells. These glioma stem cells (GSCs) evade therapeutic interventions and repopulate tumors due to their existence in a slowly cycling quiescent state. Although aging is well known to increase cancer initiation, the extent to which the mechanisms supporting GSC tumorigenicity are related to physiological aging remains unknown.

Pulmonary tumor embolism: A retrospective study over a 30-year period.

Background: Pulmonary tumor embolism (PTE) is difficult to detect before death, and it is unclear whether the discrepancy between antemortem clinical and postmortem diagnosis improves with the advance of the diagnostic technologies. In this study we determined the incidence of PTE and analyzed the discrepancy between antemortem clinical and postmortem diagnosis.

Methods: We performed a retrospective autopsy study on patients with the history of malignant solid tumors from 1990 to 2020 and reviewed all the slides of the patients with PTE.

Hypertrophy of the Anterior External Arcuate Fasciculus: A Rare Variant With Implications for the Development of the Arcuate Nucleus.

A rare anatomic variant of a markedly enlarged anterior external arcuate fasciculus (AEAF) on the ventral medullary surface is reported and compared to two controls. The hypertrophic AEAF was nine times larger in diameter than normal, whereas the arcuate nucleus (AN) and inferior olivary nucleus (ION) appeared histologically normal in size and neuronal distribution, and morphometric analysis of the AN confirmed that it was within the normal range. Calbindin-2 (calretinin, CALB2) expression was identified in the AN and in the fibers of the normal AEAF.

A pattern-based approach to the interpretation of skeletal muscle biopsies.

The interpretation of muscle biopsies is complex and provides the most useful information when integrated with the clinical presentation of the patient. These biopsies are performed for workup of a wide range of diseases including dystrophies, metabolic diseases, and inflammatory processes. Recent insights have led to changes in the classification of inflammatory myopathies and have changed the role that muscle biopsies have in the workup of inherited diseases.

Atrophy of the tongue following complete versus partial hypoglossal nerve transection in a canine model.

Objectives/hypothesis: The hypoglossal nerve (XII) has been used as a donor nerve in facial and laryngeal reinnervation. The purpose of this study was to investigate the neuromuscular changes that occur within the tongue following partial or complete transection of XII using a canine model.

Study Design: Histopathological comparison of tongue denervation following two types of XII resection in a canine model.

Identification of Global DNA Methylation Signatures in Glioblastoma-Derived Cancer Stem Cells.

Glioblastoma (GBM) is the most common and most aggressive primary brain tumor in adults. The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one proposed mechanism leading to the resilient behavior of tumor cells and poor prognosis. In this study, we performed an in-depth analysis of the DNA methylation landscape in GBM-derived cancer stem cells (GSCs).

Histological quantitation of brain injury using whole slide imaging: a pilot validation study in mice.

Quantitative assessment of serial brain sections provides an objective measure of neurological events at cellular and molecular levels but is difficult to implement in experimental neuroscience laboratories because of variation from person-to-person and the time required for analysis. Whole slide imaging (WSI) technology, recently introduced for pathological diagnoses, offers an electronic environment and a variety of computational tools for performing high-throughput histological analysis and managing the associated information. In our study, we applied various algorithms to quantify histologic changes associated with brain injury and compared the results to manual assessment.

Inhibition of prostate cancer bone metastasis by synthetic TF antigen mimic/galectin-3 inhibitor lactulose-L-leucine.

Currently incurable, prostate cancer metastasis has a remarkable ability to spread to the skeleton. Previous studies demonstrated that interactions mediated by the cancer-associated Thomsen-Friedenreich glycoantigen (TF-Ag) and the carbohydrate-binding protein galectin-3 play an important role in several rate-limiting steps of cancer metastasis such as metastatic cell adhesion to bone marrow endothelium, homotypic tumor cell aggregation, and clonogenic survival and growth. This study investigated the ability of a synthetic small-molecular-weight nontoxic carbohydrate-based TF-Ag mimic lactulose-L-leucine (Lac-L-Leu) to inhibit these processes in vitro and, ultimately, prostate cancer bone metastasis in vivo.

Identification and analysis of signaling networks potentially involved in breast carcinoma metastasis to the brain.

Brain is a common site of breast cancer metastasis associated with significant neurologic morbidity, decreased quality of life, and greatly shortened survival. However, the molecular and cellular mechanisms underpinning brain colonization by breast carcinoma cells are poorly understood. Here, we used 2D-DIGE (Difference in Gel Electrophoresis) proteomic analysis followed by LC-tandem mass spectrometry to identify the proteins differentially expressed in brain-targeting breast carcinoma cells (MB231-Br) compared with parental MDA-MB-231 cell line.

Isolation and characterization of a population of stem-like progenitor cells from an atypical meningioma.

The majority of meningiomas are benign tumors associated with favorable outcomes; however, the less common aggressive variants with unfavorable outcomes often recur and may be due to subpopulations of less-differentiated cells residing within the tumor. These subpopulations of tumor cells have tumor-initiating properties and may be isolated from heterogeneous tumors when sorted or cultured in defined medium. We report the isolation and characterization of a population of tumor-initiating cells derived from an atypical meningioma.

Galectin-3 as a potential therapeutic target in tumors arising from malignant endothelia.

Angiosarcoma (ASA) in humans and hemangiosarcoma (HSA) in dogs are deadly neoplastic diseases characterized by an aggressive growth of malignant cells with endothelial phenotype, widespread metastasis, and poor response to chemotherapy. Galectin-3 (Gal-3), a beta-galactoside-binding lectin implicated in tumor progression and metastasis, endothelial cell biology and angiogenesis, and regulation of apoptosis and neoplastic cell response to cytotoxic drugs, has not been studied before in tumors arising from malignant endothelia. Here, we tested the hypothesis that Gal-3 could be widely expressed in human ASA and canine HSA and could play an important role in malignant endothelial cell biology.

Predicting survival of children with CNS tumors using proton magnetic resonance spectroscopic imaging biomarkers.

Using brain proton magnetic resonance spectroscopic imaging (MRSI) in children with central nervous system (CNS) tumors, we tested the hypothesis that combining information from biologically important metabolites, at diagnosis and prior to treatment, would improve prediction of survival. We evaluated brain proton MRSI exams in 76 children (median age at diagnosis: 74 months) with brain tumors. Important biomarkers, choline-containing compounds (Cho), N-acetylaspartate (NAA), total creatine (tCr), lipids and/or lactate (L), were measured at the "highest Cho region" and normalized to the tCr of surrounding healthy tissue.

Proliferative potential of human astrocytes.

Although a number of studies have demonstrated proliferation of nonneoplastic astrocytes in experimental animal models, the proliferative potential of human astrocytes has not been well defined. Using double-label immunohistochemistry, we identified proliferating cells with the proliferation marker MIB-1 and astrocytes with glial fibrillary acidic protein staining in human biopsy and autopsy tissue. MIB-1 labeling of astrocytes was monitored in a variety of conditions containing significant numbers of reactive astrocytes, including infections, arteriovenous malformations, demyelinating lesions, metastatic tumors, and long-standing gliosis.

Noninvasive magnetic resonance spectroscopic imaging biomarkers to predict the clinical grade of pediatric brain tumors.

The diagnosis and therapy of childhood brain tumors, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures, which limits diagnostic biopsy. Also, although new prognostic biomarkers identified by molecular analysis or DNA microarray gene profiling are promising, they too depend on invasive biopsy. Here, we test the hypothesis that combining information from biologically important intracellular molecules (biomarkers), noninvasively obtained by proton magnetic resonance spectroscopic imaging, will increase the diagnostic accuracy in determining the clinical grade of pediatric brain tumors.

Neurologic and histopathologic evaluation after high-volume intrathecal amitriptyline.

Background And Objectives: Accumulating evidence indicates that amitriptyline decreases pain sensation when administered orally, intraperitoneally, or for sciatic nerve block. Previous reports of intrathecal administration of amitriptyline have yielded inconsistent results. The failure of amitriptyline to provide antinociception may partly be related to its high logP (octanol-water partition coefficient) and consequent poor spread within the cerebrospinal fluid.

Diagnostic value of electromyography and muscle biopsy in arthrogryposis multiplex congenita.

Arthrogryposis multiplex congenita (AMC), a clinical syndrome characterized by multiple congenital joint contractures, frequently is caused by lesions in the peripheral nervous system. Two standard tests for the evaluation of the motor unit are nerve conduction studies/electromyography (NCS/EMG) and muscle biopsy. We reviewed the diagnostic value of these two studies in the evaluation of AMC over a 23-year period, analyzing 38 patients with AMC who had NCS/EMG, muscle biopsy, or both.

Congenital cystic eye: recurrence after initial surgical removal.

Congenital cystic eye arises from failure of invagination of the primary optic vesicle. The cyst lacks the usual intraocular structures and contains only abortive derivatives of the anterior and posterior portions of the primary optic vesicle. Because the cystic eye usually occupies a large portion of the orbit and distends the upper eyelid, surgical excision is often carried out.

N-phenylethyl amitriptyline in rat sciatic nerve blockade.

Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na(+) channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.

Biochemical characterization of pediatric brain tumors by using in vivo and ex vivo magnetic resonance spectroscopy.

Object: Magnetic resonance (MR) spectroscopy provides biochemical information about tumors. The authors sought to determine the relationship between in vivo and ex vivo biochemical characterization of pediatric brain tumors by using MR spectroscopy. Their hypothesis was that ex vivo MR spectroscopy provides a link between in vivo MR spectroscopy and neuropathological analysis.

Neuroimaging in pediatric brain tumors: Gd-DTPA-enhanced, hemodynamic, and diffusion MR imaging compared with MR spectroscopic imaging.

Background And Purpose: Gadolinium-enhanced MR images assist in defining tumor borders; however, the relation between tumor cell extent and contrast-enhanced regions is unclear. Our aim was to improve conventional neuroimaging of pediatric brain tumors with hemodynamic, diffusion, and spectroscopic MR imaging.

Methods: We performed conventional MR and MR spectroscopic imaging in 31 children with neuroglial brain tumors.

Biocompatibility of lipid-protein-sugar particles containing bupivacaine in the epineurium.

Novel lipid-protein-sugar particles (LPSPs) are potentially biocompatible because they are composed of naturally occurring ingredients and their expected tissue dwell times are relatively short. In this research, we used histological sections to study tissue reaction to LPSPs (4.4-microm median diameter) when used for sciatic nerve block in the rat.