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Current Oncology (Toronto, Ont.) Apr 2023Mesenchymal breast tumors are a rare and diverse group of tumors that present some of the most challenging cases for multidisciplinary breast cancer teams. As a result... (Review)
Review
Mesenchymal breast tumors are a rare and diverse group of tumors that present some of the most challenging cases for multidisciplinary breast cancer teams. As a result of overlapping morphologies and a lack of large-scale studies on these tumors, practices are often heterogeneous and slow to evolve. Herein, we present a non-systematic review that focuses on progress, or lack thereof, in the field of mesenchymal breast tumors. We focus on tumors originating from fibroblastic/myofibroblastic cells and tumors originating from less common cellular origins (smooth muscle, neural tissue, adipose tissue, vascular tissue, etc.).
Topics: Humans; Female; Breast Neoplasms
PubMed: 37232796
DOI: 10.3390/curroncol30050338 -
The Journal of Physiology Sep 2019Golgi tendon organ feedback has been evaluated most frequently using electrical stimulation of peripheral nerves, which is not a physiological or selective stimulus for...
KEY POINTS
Golgi tendon organ feedback has been evaluated most frequently using electrical stimulation of peripheral nerves, which is not a physiological or selective stimulus for Golgi tendon organs. Golgi tendon organs are most responsive to active muscle contractions. This study provides evidence that muscle stimulation evoked twitches - a physiological stimulus for Golgi tendon organs - induces intermuscular effects most likely due to mechanical activation of Golgi tendon organ feedback and not direct activation of sensory axons. The results demonstrate that twitch contractions are a feasible non-invasive approach that can be used to advance understanding of the functional role of Golgi tendon organ feedback.
ABSTRACT
Force feedback from Golgi tendon organs (GTOs) has widespread intermuscular projections mediated by interneurons that share inputs from muscle spindles, among others. Because current methods to study GTO circuitry (nerve stimulation or muscle stretch) also activate muscle spindle afferents, the selective role of GTOs remains uncertain. Here, we tested the hypothesis that intramuscular stimulation evoked twitch contractions could be used to naturally bias activation of GTOs and thus evaluate their intermuscular effects in decerebrate cats. This was achieved by comparing the effects of twitch contractions and stretches as donor inputs onto the motor output of recipient muscles. Donor-recipient pairs evaluated included those already known in the cat to receive donor excitatory muscle spindle feedback only, inhibitory GTO feedback only, and both excitatory spindle and inhibitory GTO effects. Muscle stretch, but not twitch contractions, evoked excitation onto recipient muscles with muscle spindle afferent inputs only. Both donor muscle stretch and twitch contractions inhibited a recipient muscle with GTO projections only. In a recipient muscle that receives both muscle spindle and GTO projections, donor muscle stretch evoked both excitatory and inhibitory effects, whereas twitch contractions evoked inhibitory effects only. These data support the hypothesis that muscle stimulation evoked contractions can induce intermuscular effects most consistent with mechanical GTO receptor activation and not direct activation of sensory axons. We propose this approach can be used to evaluate GTO circuitry more selectively than muscle stretch or nerve stimulation and can be adapted to study GTO feedback non-invasively in freely moving cats and humans.
Topics: Animals; Axons; Cats; Electric Stimulation; Feedback; Mechanoreceptors; Muscle Contraction; Muscle Spindles; Muscle, Skeletal; Sensory Receptor Cells
PubMed: 31228207
DOI: 10.1113/JP277363 -
Cureus Jun 2022Primary hepatic undifferentiated pleomorphic sarcoma (UPS) is a rare malignant mesenchymal tumor with a nonspecific clinical and radiologic presentation. Primary hepatic...
Primary hepatic undifferentiated pleomorphic sarcoma (UPS) is a rare malignant mesenchymal tumor with a nonspecific clinical and radiologic presentation. Primary hepatic UPS is often a diagnosis of exclusion made by multiple immunohistological testing that rules out hepatic, hematologic, neural, and epithelial origin. Stains for mesenchymal origin are usually the only positive stain and do not demonstrate evidence of specific mesenchymal cell differentiation. We report a case of a 56-year-old male with no significant past medical history that presented with complaint of epigastric abdominal pain of six months duration. A computed tomography (CT) scan of the abdomen and pelvis exhibited numerous hepatic masses involving right and left hepatic lobe. A CT-guided core needle biopsy discovered undifferentiated/pleomorphic sarcoma. Histomorphology showed spindle cell neoplasm without recognizable hepatic tissue. Immunohistochemistry (IHC) stains were positive for smooth muscle actin (SMA) but failed to establish a more specific histogenesis. Furthermore, IHC stains revealed spindle neoplastic cells with focal and patchy positive h-caldesmon (approximately 10-15% of neoplastic cells), and negative for desmin. Given these results, the diagnosis of undifferentiated/pleomorphic sarcoma was established. It is imperative to consider UPS in the differential diagnosis of large liver lesions without evidence of differentiation. Early identification of this rare tumor can prevent the possibility of distant metastasis and improve survival among patients.
PubMed: 35844313
DOI: 10.7759/cureus.25895 -
Theranostics 2021Bio-engineered myocardium has great potential to substitute damaged myocardium and for studies of myocardial physiology and disease, but structural and functional...
Bio-engineered myocardium has great potential to substitute damaged myocardium and for studies of myocardial physiology and disease, but structural and functional immaturity still implies limitations. Current protocols of engineered heart tissue (EHT) generation fall short of simulating the conditions of postnatal myocardial growth, which are characterized by tissue expansion and increased mechanical load. To investigate whether these two parameters can improve EHT maturation, we developed a new approach for the generation of cardiac tissues based on biomimetic stimulation under application of continuously increasing stretch. EHTs were generated by assembling cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CM) at high cell density in a low collagen hydrogel. Maturation and growth of the EHTs were induced in a custom-made biomimetic tissue culture system that provided continuous electrical stimulation and medium agitation along with progressive stretch at four different increments. Tissues were characterized after a three week conditioning period. The highest rate of stretch (S3 = 0.32 mm/day) increased force development by 5.1-fold compared to tissue with a fixed length, reaching contractility of 11.28 mN/mm². Importantly, intensely stretched EHTs developed physiological length-dependencies of active and passive forces (systolic/diastolic ratio = 9.47 ± 0.84), and a positive force-frequency relationship (1.25-fold contractility at 180 min). Functional markers of stretch-dependent maturation included enhanced and more rapid Ca transients, higher amplitude and upstroke velocity of action potentials, and pronounced adrenergic responses. Stretch conditioned hiPSC-CMs displayed structural improvements in cellular volume, linear alignment, and sarcomere length (2.19 ± 0.1 µm), and an overall upregulation of genes that are specifically expressed in adult cardiomyocytes. With the intention to simulate postnatal heart development, we have established techniques of tissue assembly and biomimetic culture that avoid tissue shrinkage and yield muscle fibers with contractility and compliance approaching the properties of adult myocardium. This study demonstrates that cultivation under progressive stretch is a feasible way to induce growth and maturation of stem cell-derived myocardium. The novel tissue-engineering approach fulfills important requirements of disease modelling and therapeutic tissue replacement.
Topics: Biomimetic Materials; Bioreactors; Cell Size; Diastole; Electric Stimulation; Excitation Contraction Coupling; Humans; Hydrogels; Induced Pluripotent Stem Cells; Muscle Spindles; Myocardium; Myocytes, Cardiac; Myofibrils; Organoids; RNA, Messenger; Stress, Mechanical; Systole; Tissue Culture Techniques; Tissue Engineering
PubMed: 33995650
DOI: 10.7150/thno.54999 -
Toxins Feb 2021In dystonic and spastic movement disorders, however different in their pathophysiological mechanisms, a similar impairment of sensorimotor control with special emphasis... (Review)
Review
In dystonic and spastic movement disorders, however different in their pathophysiological mechanisms, a similar impairment of sensorimotor control with special emphasis on afferentation is assumed. Peripheral intervention on afferent inputs evokes plastic changes within the central sensorimotor system. Intramuscular application of botulinum toxin type A (BoNT-A) is a standard evidence-based treatment for both conditions. Apart from its peripheral action on muscle spindles, a growing body of evidence suggests that BoNT-A effects could also be mediated by changes at the central level including cerebral cortex. We review recent studies employing electrophysiology and neuroimaging to investigate how intramuscular application of BoNT-A influences cortical reorganization. Based on such data, BoNT-A becomes gradually accepted as a promising tool to correct the maladaptive plastic changes within the sensorimotor cortex. In summary, electrophysiology and especially neuroimaging studies with BoNT-A further our understanding of pathophysiology underlying dystonic and spastic movement disorders and may consequently help develop novel treatment strategies based on neural plasticity.
Topics: Animals; Botulinum Toxins, Type A; Brain Mapping; Cerebral Cortex; Dystonia; Humans; Magnetic Resonance Imaging; Motor Activity; Muscle, Skeletal; Neuromuscular Agents; Neuronal Plasticity; Recovery of Function; Treatment Outcome
PubMed: 33671128
DOI: 10.3390/toxins13020155 -
Genes, Chromosomes & Cancer Nov 2022Spindle cell rhabdomyosarcoma represents a rare neoplasm characterized by monomorphic spindle cells with a fascicular architecture and variable skeletal muscle...
Spindle cell rhabdomyosarcoma represents a rare neoplasm characterized by monomorphic spindle cells with a fascicular architecture and variable skeletal muscle differentiation. Following incidental identification of a ZFP64::NCOA3 gene fusion in an unclassified spindle cell sarcoma resembling adult-type fibrosarcoma, we performed a retrospective archival review and identified four additional cases with a similar histology and identical gene fusion. All tumors arose in adult males (28-71 years). The neoplasms were found in the deep soft tissues, two were gluteal, and one each arose in the thigh, abdominal wall, and chest wall. Morphologically, the tumors were characterized by spindle cells with a distinctive herringbone pattern and variable collagenous to myxoid stroma. The nuclei were relatively monomorphic with variable mitotic activity. Three tumors had immunoreactivity for MyoD1, and four contained variable expression of desmin and smooth muscle actin. All cases tested for myogenin, CD34, S100, pankeratin, and epithelial membrane antigen were negative. Targeted RNA sequencing revealed a ZFP64::NCOA3 fusion product in all five tumors. Three patients developed distant metastases, and two ultimately succumbed to their disease within 2 years of initial diagnosis. This study suggests ZFP64::NCOA3 fusions define a novel subtype of rhabdomyosarcoma with a spindle cell morphology and aggressive clinical behavior. The potential for morphologic and immunohistochemical overlap with several other sarcoma types underscores the value of molecular testing as a diagnostic adjunct to ensure accurate classification and management of these neoplasms.
Topics: Adult; Biomarkers, Tumor; Child; DNA-Binding Proteins; Fibrosarcoma; Gene Fusion; Humans; Male; Nuclear Receptor Coactivator 3; Retrospective Studies; Rhabdomyosarcoma; Sarcoma; Soft Tissue Neoplasms; Transcription Factors
PubMed: 35521817
DOI: 10.1002/gcc.23052 -
Der Pathologe Jun 2020Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal neoplasms with features of both melanotic and smooth muscle differentiation. PEComa... (Review)
Review
Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal neoplasms with features of both melanotic and smooth muscle differentiation. PEComa morphology is highly variable and encompasses epithelioid to spindle cells often with clear cytoplasm and prominent nucleoli. Molecularly, most PEComas are defined by a loss of function of the TSC1/TSC2 complex. Additionally, a distinct small subset of PEComas harboring rearrangements of the TFE3 (Xp11) gene locus has been identified. By presenting a series of three case reports with distinct features, we demonstrate diagnostic pitfalls as well as the importance of molecular work-up of PEComas because of important therapeutic consequences.
Topics: Humans; Perivascular Epithelioid Cell Neoplasms
PubMed: 31309284
DOI: 10.1007/s00292-019-0612-5 -
Indian Journal of Surgical Oncology Dec 2022Plexiform angiomyxoid myofibroblast tumour (PAMT) is a rare mesenchymal tumour of the stomach. To date, about 45 cases of PAMT have been reported in the literature. This...
Plexiform angiomyxoid myofibroblast tumour (PAMT) is a rare mesenchymal tumour of the stomach. To date, about 45 cases of PAMT have been reported in the literature. This is an extremely rare mesenchymal gastric tumour with definite histological pattern and is a tumour typified by spindle cells with myofibroblast characteristics. A 70-year-old woman was admitted with vague upper abdominal pain and dyspepsia and on OGD was found to have a polypoidal lesion with ulceration on the posterior wall of the body of the stomach towards the greater curvature. The endoscopy biopsy suggested the above diagnosis. The patient was investigated with CT scan and CT showed a large nodular growth 10 × 8 cm with pancreatic tail involvement and splenic involvement. The patient was treated with multi-visceral resection and favourable outcome was achieved. This entity of PAMT was a histological rarity and a technically challenging case and hence was analysed and presented. PAMT is a rare mesenchymal tumour of the stomach and is characterised by spindle cells with myofibroblast characteristics with a potential to differentiate towards smooth muscle cells. These tumours have a benign course and rarely can have an infiltrative behaviour. PAMT of the stomach is a very rare mesenchymal tumour with a unique histological appearance, and it needs to be distinguished from GIST and other gastrointestinal mesenchymal tumours, although extra gastric extension and vascular invasion are sometimes observed. Here, we are reporting this case as a case of PAMT arising from the body of the stomach which required multi-visceral resection.
PubMed: 36687230
DOI: 10.1007/s13193-022-01625-4 -
Frontiers in Neuroanatomy 2021This study sought to investigate the sexual dimorphism of muscle spindles in rat medial gastrocnemius muscle. The muscles were cut transversely into 5-10 and 20 μm...
This study sought to investigate the sexual dimorphism of muscle spindles in rat medial gastrocnemius muscle. The muscles were cut transversely into 5-10 and 20 μm thick serial sections and the number, density, and morphometric properties of the muscle spindles were determined. There was no significant difference ( > 0.05) in the number of muscle spindles of male (14.45 ± 2.77) and female (15.00 ± 3.13) rats. Muscle mass was 38.89% higher in males (1.08 vs. 0.66 g in females), making the density of these receptors significantly higher ( < 0.01) in females (approximately one spindle per 51.14 mg muscle mass vs. one per 79.91 mg in males). There were no significant differences between the morphometric properties of intrafusal muscle fibers or muscle spindles in male and female rats ( > 0.05): 5.16 ± 2.43 and 5.37 ± 2.27 μm for male and female intrafusal muscle fiber diameter, respectively; 5.57 ± 2.20 and 5.60 ± 2.16 μm for male and female intrafusal muscle fiber number, respectively; 25.85 ± 10.04 and 25.30 ± 9.96 μm for male and female shorter muscle spindle diameter, respectively; and 48.99 ± 20.73 and 43.97 ± 16.96 μm for male and female longer muscle spindle diameter, respectively. These findings suggest that sexual dimorphism in the muscle spindles of rat medial gastrocnemius is limited to density, which contrasts previous findings reporting differences in extrafusal fibers diameter.
PubMed: 34658799
DOI: 10.3389/fnana.2021.734555 -
Experimental Brain Research Sep 2022Heteronymous excitatory feedback from muscle spindles and inhibitory feedback from Golgi tendon organs and recurrent inhibitory circuits can influence motor...
Heteronymous excitatory feedback from muscle spindles and inhibitory feedback from Golgi tendon organs and recurrent inhibitory circuits can influence motor coordination. The functional role of inhibitory feedback is difficult to determine, because nerve stimulation, the primary method used in humans, cannot evoke inhibition without first activating the largest diameter muscle spindle axons. Here, we tested the hypothesis that quadriceps muscle stimulation could be used to examine heteronymous inhibition more selectively when compared to femoral nerve stimulation by comparing the effects of nerve and muscle stimulation onto ongoing soleus EMG held at 20% of maximal effort. Motor threshold and two higher femoral nerve and quadriceps stimulus intensities matched by twitch evoked torque magnitudes were examined. We found that significantly fewer participants exhibited excitation during quadriceps muscle stimulation when compared to nerve stimulation (14-29% vs. 64-71% of participants across stimulation intensities) and the magnitude of heteronymous excitation from muscle stimulation, when present, was much reduced compared to nerve stimulation. Muscle and nerve stimulation resulted in heteronymous inhibition that significantly increased with increasing stimulation evoked torque magnitudes. This study provides novel evidence that muscle stimulation may be used to more selectively examine inhibitory heteronymous feedback between muscles in the human lower limb when compared to nerve stimulation.
Topics: Electric Stimulation; Femoral Nerve; H-Reflex; Humans; Muscle Spindles; Muscle, Skeletal; Quadriceps Muscle
PubMed: 35881156
DOI: 10.1007/s00221-022-06422-7