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Histological and functional analysis of vascular smooth muscle cells in a novel culture system with honeycomb-like structure.

Vascular smooth muscle cells (SMCs) undergo phenotype change with the development of atherosclerosis. The phenotype changes of SMCs have been observed in various culture conditions, such as collagen-coated dishes. Here, we report the morphological and functional features of SMCs in a novel culture system using type I-collagen in a characteristic three-dimensional structure designated as honeycombs. The number of ribosome and mitochondria in SMCs cultured in honeycombs was one half or third of those cultured on collagen-coated plastic plates. DNA and protein synthesis of SMCs cultured in honeyc

AIDS-related Kaposi's sarcoma cells rapidly internalize endostatin, which co-localizes to tropomysin microfilaments and inhibits cytokine-mediated migration and invasion.

AIDS-related Kaposi's sarcoma (KS) is the most common HIV-related malignancy. In some respects, KS is analogous to other angioproliferative diseases, in that KS lesions are highly vascularized and promoted by inflammatory cytokines. However, unlike other cancers or inflammatory mediated vascular diseases, KS is unique in that the KS lesional cells both express and respond to the complete angiogenic cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Therefore, the angiogenic phenotype, which is crucial for cancer progression, is inherent to KS tumor c

[Mechanism of electroacupuncture in improving central sensitization in rats with non-erosive reflux disease of liver-stomach disharmony pattern based on NGF/TrkA signaling pathway].

OBJECTIVES: To investigate the effect of electroacupuncture (EA) on central sensitization in rats with non-erosive reflux disease (NERD) of … d motilin (MTL) were measured by ELISA. The protein expression levels of nerve growth factor (NGF), tropomyosin receptor kinase A (TrkA), glutamate receptor AMPA type subunit 1 (GluA1), and postsynaptic density protein 95 (PSD95) in the spinal cord tissue were detected by Western blot, and the mRNA expression levels of NGF and TrkA in the spinal cord were mea …

[Antidepressant mechanism of essential oil from Schizonepeta tenuifolia based on 5-HT1AR/cAMP/PKA signaling pathway].

This study aims to investigate the antidepressant effects of essential oil from Schizonepeta tenuifolia and its mechanism of action on inter … -HT1AR, PKA, cAMP response element-binding protein( CREB), brain-derived neurotrophic factor(BDNF), tropomyosin receptor kinase B( TrkB), synaptophysin( SYP), and postsynaptic density protein 95(PSD95) in the hippocampus, the cAMP protein level was also increased. In summary, essential oil from S. tenuifolia exerts antidepressant effects by activating the 5-H …

Targeting increased levels of APP in Down syndrome: Posiphen-mediated reductions in APP and its products reverse endosomal phenotypes in the Ts65Dn mouse model.

OBJECTIVE: Recent clinical trials targeting amyloid beta (Aβ) and tau in Alzheimer's disease (AD) have yet to demonstrate efficacy. Reviewin … normal levels of Rab5 activity, reduced phosphorylated tau (p-tau), and reversed deficits in TrkB (tropomyosin receptor kinase B) activation and in the Akt (protein kinase B [PKB]), ERK (extracellular signal-regulated kinase), and CREB (cAMP response element-binding protein) signaling pathways. Remarkably, Posiphen treatment also restored the level of cholin …

[Effects of Vitamin B12 on Behaviors, Brain Monoamine Neurotransmitters, and Brain-Derived Neurotrophic Factor in Depressive Rats].

OBJECTIVE: To investigate the behavioral changes and monoamine neurotransmitter levels in a rat model of chronic unpredictable mild stress ( … expression of signal pathway-related proteins, including brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), and cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in the hippocampal tissue. RESULTS: Starting from week 5, rats in the CUMS group exhibited lower average body mass compared to the control g …

Selective JAK2/ABL dual inhibition therapy effectively eliminates TKI-insensitive CML stem/progenitor cells.

Polymyalgia rheumatica (PMR) is a common disorder in the elderly population. The diagnosis is based upon recognition of a clinical syndrome, consisting of pain and stiffness in the shoulder and pelvic girdle, muscle tenderness of the upper and lower limbs and nonspecific somatic complaints. In addition, in most cases the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentration are highly elevated. Although PMR and giant cell arteritis (GCA) are commonly regarded as two clinical variations of the same disease, their clinical picture is quite different. Whilst in PMR the m

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… TPM1 is a member of the tropomyosin family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. … Tropomyosin functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. …

A Randomized Placebo-Controlled Trial of the Anti-Nerve Growth Factor Antibody Tanezumab in Subjects With Cancer Pain Due to Bone Metastasis.

BackgroundThis phase III, randomized, double-blind, placebo-controlled, parallel-group study assessed the efficacy and safety of tanezumab in subjects with cancer pain predominantly due to bone metastasis receiving background opioid therapy.MethodsSubjects were randomized (stratified by (1) tumor aggressiveness and (2) presence/absence of concomitant anticancer treatment) to placebo or tanezumab 20 mg. Treatment was administered by subcutaneous injection every 8 weeks for 24 weeks (3 doses) followed by a 24-week safety follow-up period. The primary outcome was change in daily average pain in t

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… NGF = nerve growth factor; TrkA = tropomyosin receptor kinase A. Conclusion This study demonstrates the potential of anti-NGF therapies such as tanezumab to reduce pain caused by bone metastases. … The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A. Neuroscience. 2011;178:196-207. 10.1016/j.neuroscience.2011.01.039. 25. Bloom AP, Jimenez-Andrade JM, Taylor RN, et al. …

New Insights into the Pathogenesis of Systemic Mastocytosis.

Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management o

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… Although KIT mutations, particularly KIT D816V, have been considered to serve as key mutations in mastocytosis, an increasing body of data has indicated that other events (e.g., tropomyosin-related kinase [TRK]) may play important roles in the pathogenesis of mastocytosis ( Table 1 ). … TRK (Tropomyosin-Related Kinase) The neurotrophins (NTs), which include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, and NT-4, play major roles in neuronal survival. …

Nerve Growth Factor and Autoimmune Diseases.

NGF plays a crucial immunomodulatory role and increased levels are found in numerous tissues during autoimmune states. NGF directly modulates innate and adaptive immune responses of B and T cells and causes the release of neuropeptides and neurotransmitters controlling the immune system activation in inflamed tissues. Evidence suggests that NGF is involved in the pathogenesis of numerous immune diseases including autoimmune thyroiditis, chronic arthritis, multiple sclerosis, systemic lupus erythematosus, mastocytosis, and chronic granulomatous disease. Furthermore, as NGF levels have been link

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… The final form of NTs binds to high-affinity tropomyosin-related kinase (Trk) A, B or C receptors or the low-affinity p75 pan-neurotrophin receptor (p75NTR), also referred to as CD271 in immune cells [ 17 , 26 , 27 ]. … Selective inhibition of tropomyosin-receptor-kinase A (TrkA) reduces pain and joint damage in two rat models of inflammatory arthritis Arthritis Res. Ther. 2016 18 97 10.1186/s13075-016-0996-z 27145816 PMC4857260 165. Compston A. Coles A. …

Neurophysiological Mechanisms Related to Pain Management in Bone Tumors.

BackgroundPrimary and metastatic bone tumor incidence has increased in the previous years. Pain is a common symptom and is one of the most important related factors to the decrease of quality of life in patients with bone tumor. Different pain management strategies are not completely effective and many patients afflicted by cancer pain cannot be controlled properly. In this sense, we need to elucidate the neurophysiology of cancer-induced pain, contemplating other components such as inflammation, neuropathies and cognitive components regarding bone tumors, and thus pave the way for novel thera

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… The adult skeleton is innervated by finely myelinated tropomyosin kinase A (TrkA+) sensitive sensory nerve fibers (Aδ), while it does not receive innervation from larger touch-sensitive A-beta fibers and does not present C fibers without myelin (TrkA-) [ 43 ]. … The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A. Neuroscience 2011 178 196 207 10.1016/j.neuroscience.2011.01.039 21277945 PMC3078085 44 Jimenez-Andrade J.M. Mantyh W.G. Bloom A.P. Ferng A.S. Geffre C.P. Mantyh P.W. …

The osteoblast in regulation of tumor cell dormancy and bone metastasis.

Breast and prostate cancer are among the most common malignancies worldwide. After treatment of the primary tumor, distant metastases often occur after a long disease-free interval. Bone is a major site for breast and prostate cancer metastasis and approximately 70% of patients with advanced disese suffer from osteolytic or osteoblastic bone metastases, a stage at which the disease is incurable. In bone, the disseminated tumor cells (DTCs) can become quiescent or "dormant", a state where they are alive but not actively dividing. Alternatively, the cancer cells can proliferate, disturb the bone

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… Additionally, increased expression of chemokines CXCL-12, TSP-1 and tropomyosin secreted by osteoblasts maintains a dormant state. Osteoblast derived ligand Wnt5a activates ROR2/SIAH2 signaling to suppress Wnt/β-catenin signaling promoting dormancy. … Binding of LIF to the LIF receptor (LIFR) on cancer cells induces the expression of TSP-1, tropomyosin and other dormancy promoting genes while inhibitor of LIFR in MCF-7 cells reduced p53 expression [39] . …

Impact and Diagnostic Gaps of Comprehensive Genomic Profiling in Real-World Clinical Practice.

Purposenext-generation sequencing based comprehensive genomic profiling (CGP) is becoming common practice. Although numerous studies have shown its feasibility to identify actionable genomic alterations in most patients, its clinical impact as part of routine management across all cancers in the community remains unknown.Methodswe conducted a retrospective study of all patients that underwent CGP as part of routine cancer management from January 2013 to June 2017 at an academic community-based NCI-designated cancer center. CGP was done in addition to established first tier reflex molecular tes

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… The impact of CGP will likely also increase with the tissue/site agnostic approval of pembrolizumab in solid tumors with microsatellite instability and Tropomyosin Receptor Kinase (TRK) inhibitors for Neurotrophic Tropomyosin-Related Kinase (NTRK)-translocation positive malignancies; however, the frequency …

Bone Pain in Cancer Patients: Mechanisms and Current Treatment.

The skeletal system is the third most common site for cancer metastases, surpassed only by the lungs and liver. Many tumors, especially those of the breast, prostate, lungs, and kidneys, have a strong predilection to metastasize to bone, which causes pain, hypercalcemia, pathological skeletal fractures, compression of the spinal cord or other nervous structures, decreased mobility, and increased mortality. Metastatic cancer-induced bone pain (CIBP) is a type of chronic pain with unique and complex pathophysiology characterized by nociceptive and neuropathic components. Its treatment should be

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… This inhibition occurs by means of overexpressing tropomyosin receptor kinase B (TrkB) on the tumor cell membrane, which results in the activation of phosphatidylinositol-4,5-bisphosphate 3 kinase (PI3K)–AKT pro-survival pathways [ 26 ]. … Sensory nerves that innervate bones are predominantly thinly myelinated and unmyelinated nerve fibers: A-δ (delta) or C-sensory nerve fibers (80% tropomyosin kinase A (TrkA)-positive) [ 14 ]. …

B-cells in pulmonary arterial hypertension: friend, foe or bystander?

There is an unmet need for new therapeutic strategies that target alternative pathways to improve the prognosis of patients with pulmonary arterial hypertension (PAH). As immunity has been involved in the development and progression of vascular lesions in PAH, we review the potential contribution of B-cells in its pathogenesis and evaluate the relevance of B-cell-targeted therapies. Circulating B-cell homeostasis is altered in PAH patients, with total B-cell lymphopenia, abnormal subset distribution (expansion of naïve and antibody-secreting cells, reduction of memory B-cells) and chronic acti

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… Other targets include cytoskeletal (such as tropomyosin α-1 chain) and mRNA regulation (such as KH-type splicing regulatory protein) proteins [ 82 ]. Effects: serum IgG from SSc-PAH and iPAH patients induces SMC contraction within a collagen matrix, conversely to those of healthy controls [ 82 ]. … These proteins are involved in various biological processes: cytoskeletal organisation (vimentin, calumenin, phosphoinositide 3-kinase (PI3K)), cell contraction (tropomyosin 1), oxidative stress (HSP27 and HSP70) and other key cellular pathways [ 85 ]. …

A Clinical Viewpoint on the Use of Targeted Therapy in Advanced Gastric Cancer.

The development of therapies for advanced gastric cancer (GC) has made significant progress over the past few years. The identification of new molecules and molecular targets is expanding our understanding of the disease's intricate nature. The end of the classical oncology era, which relied on well-studied chemotherapeutic agents, is giving rise to novel and unexplored challenges, which will cause a significant transformation of the current oncological knowledge in the next few years. The integration of established clinically effective regimens in additional studies will be crucial in managin

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… PD-1/L1—programmed death-1/ligand1, dMMR—deficient mismatch repair, MSI-H—microsatellite instability (high), TMB-H—tumor mutational burden (high), PIK3CA—phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, AKT—tropomyosin receptor kinase, mTOR—mammalian target of rapamycin, TRK—tropomyosin … Each of these encodes one of three tropomyosin receptor kinases, namely TrkA, TrkB, and TrkC, respectively [ 117 ]. …

Многоцелевые лекарственные препараты: новые 2025 и послерыночного контроля за безопасностью наркотиков, 2022-2024.

Полифармакология предназначена для развития соединений, действующих по крайней мере на two целевые показатели (многоцелевые лиганды, МТДЛ). В 2025, Европейское агентство по медицине (ЕМА), 38 наркотиков, и 11 из них были MTDL. Большинство из них - антитела-наркотики, биконкретные антитела или ингибиторы киназы, все из которых указаны для лечения опухолей, включая датопотамаб дерукстекан (гормон-позитивный рецептор, HER2-negative Рак молочной железы), тизотумаб ведотин (сокращенная шейная карцинома), линвосельтамб (четвёртая линия лечения множественной миеломы) и эрдафитиниб (сокращенная уротел

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… , p110α, phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit alpha gene /protein; PD-1, programmed death receptor 1; PD-L1, programmed death receptor 1 ligand 1; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; TF, tissue factor; TRα, β, thyroid hormone receptors α, β; TRKA, B, C, tropomyosin … Fusion proteins containing ROS1 or tropomyosin receptor tyrosine kinase (TRK) domains can promote tumor development by excessively activating downstream signaling pathways, resulting in uncontrolled cell growth [ 36 ]. …

Hemostatic and platelet proteins are associated with bleeding grade and time to major bleed in hemato-oncological patients.

Bleeding crises are common complications in hemato-oncological patients undergoing chemotherapy and stem cell transplantation. Platelet transfusions are frequently administered to treat and prevent bleeding events at low platelet counts. However, the association between thrombocytopenia and bleeding events remains unclear, arguing for an improved understanding of pathophysiological changes underpinning bleeding events. Therefore, this study aims to identify plasma protein levels associated with bleeding events in a hemato-oncological patient population using unbiased mass spectrometry-based pl

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… CI, 0.09-0.64], respectively), followed by talin-1 (TLN1; HR, 0.69; 95% CI, 0.53-0.91), adenylyl cyclase–associated protein 1 (CAP1; HR, 0.75; 95% CI, 0.63-0.89]), LIM zinc finger domain–containing 1 (LIMS1; HR, 0.78; 95% CI, 0.66-0.92), Ras suppressor protein 1 (RSU1; HR, 0.81; 95% CI, 0.69-0.94), tropomyosin … Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia. J Clin Invest. 2017;127(3):814–829. doi: 10.1172/JCI86154. 31. Eckly A, Strassel C, Freund M, et al. Abnormal megakaryocyte morphology and proplatelet formation in mice with megakaryocyte-restricted MYH9 inactivation. …

Bone Metastasis Pain, from the Bench to the Bedside.

Bone is the most frequent site of metastasis of the most common cancers in men and women. Bone metastasis incidence has been steadily increasing over the years, mainly because of higher life expectancy in oncologic patients. Although bone metastases are sometimes asymptomatic, their consequences are most often devastating, impairing both life quality and expectancy, due to the occurrence of the skeletal-related events, including bone fractures, hypercalcemia and spinal cord compression. Up to 75% of patients endure crippling cancer-induced bone pain (CIBP), against which we have very few weapo

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… Tumour cells also secrete many factors that are able to activate or sensitise pain-mediating receptors, such as nerve growth factor (NGF), which binds the tropomyosin-related kinase (Trk)A-p75 receptor complex. … Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer pain. Mol. Pain. 2010;6:87. doi: 10.1186/1744-8069-6-87. 96. Hondermarck H. Neurotrophins and their receptors in breast cancer. …

Chemotherapy-Mediated Complications of Wound Healing: An Understudied Side Effect.

Significance: Chemotherapy is a primary method to treat cancer. While chemotherapeutic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types. In the case of dermal cells and macrophages involved in wound healing, cytotoxicity often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent Advances: Despite its significant impact on patients' recovery from surgery, the issue of delayed wound healing in individuals undergoing chemotherapy remains inadequately ex

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… Impaired wound healing 6 Oxaliplatin 37 | G2/M arrest and apoptosis are characterized by the translocation of Bax into the mitochondria and the release of cytochrome c into the cytosol 38 | Resected stage II colon cancer 38 | Sensory neuropathy; hypersensitivity 39 Entrectinib 75 | Receptor inhibition of tropomyosin … interferons κ factor 1 interferon keratinocyte growth factor mitogen-activated protein kinase mitogen-activated protein platelet-derived growth factor proto-oncogene tyrosine-protein kinase serotonin and norepinephrine reuptake inhibitors tumor growth factor-β triple-negative breast cancer tropomyosin …