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Matrix metalloproteinases and tissue inhibitors in multiple myeloma: promote or inhibit?

Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) play a vital role in the pathogenesis of multiple myeloma (MM), especially for tumor invasion and osteolytic osteopathy. By breaking down extracellular matrix (ECM) components and releasing the proteins composing the ECM and growth factors, as well as their receptors, MMPs affect tissue integrity and promote cancer cell invasion and metastasis. A vital pathophysiological characteristic of MM is the progress of osteolytic lesions, which are brought on by interactions between myeloma cells and the bone marrow mic

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… Matrilysins (MMP-7 and MMP-26) are unique as they lack a hemopexin domain common to other MMPs. They can cleave both collagen and gelatin in vitro ( 4 ). … Furthermore, interactions between TIMP-1 and the hemopexin domain of pro-MMP-9 lead to the formation of a compound that hinders MMP-9 activation, which in turn inhibits the production of MMP-9 ( 83 ). …

Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review.

Babesia microti is an obligate intra-erythrocytic parasite transmitted by infected ticks. B. microti is a eukaryote much larger than prokaryotic microbes and more similar to human hosts in their biochemistry and metabolism. Moreover, Babesia spp. possess various immune evasion mechanisms leading to persistent and sometimes life-threatening diseases in immunocompromised hosts. Chronic lymphocytic leukemia (CLL) is the most prevalent adult B-cell malignancy, and a small percentage of CLL transforms into aggressive lymphomas. CLL also causes immune dysfunction due to the over-expansion of immatur

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… Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development. … Front Physiol. 2014;5:415. 10.3389/fphys.2014.00415 PMC4211382 25389409 Schaer DJ Vinchi F Ingoglia G Tolosano E Buehler PW Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development Front Physiol 2014 5 415 25389409 10.3389/fphys.2014.00415 PMC4211382 …

Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment.

Cancer is still one of the leading causes of death worldwide. This great mortality is due to its late diagnosis when the disease is already at advanced stages. Although the efforts made to develop more effective treatments, around 90% of cancer deaths are due to metastasis that confers a systemic character to the disease. Likewise, matrix metalloproteinases (MMPs) are endopeptidases that participate in all the events of the metastatic process. MMPs' augmented concentrations and an increased enzymatic activity have been considered bad prognosis markers of the disease. Therefore, synthetic inhib

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… First, two MMP-14 molecules dimerize through their membrane and hemopexin motifs on the cell surface. Then the TIMP-2 C-terminal zone interacts with the pro-MMP-2 hemopexin domain while its N-terminal motif links to the catalytic site of one MMP-14. … Likewise, TIMP-1 C-terminal extreme binds to the hemopexin motif of pro-MMP-9, while the catalytic site of an MMP-3 molecule interacts with the N-terminal extreme of TIMP-1, forming the pro-MMP-9/TIMP-1/MMP-3 ternary complex ( Ogata, et al., 1995 ). …

Tumor Cell Survival Factors and Angiogenesis in Chronic Lymphocytic Leukemia: How Hot Is the Link?

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of neoplastic CD5+/CD19+ B lymphocytes in the blood. These cells migrate to and proliferate in the bone marrow and lymphoid tissues. Despite the development of new therapies for CLL, drug resistance and disease relapse still occur; novel treatment approaches are therefore still needed. Inhibition of the angiogenesis involved in the progression of CLL might be a relevant therapeutic strategy. The literature data indicate that vascular endothelial growth factor, angiopoietin-2, and matrix metalloproteinase-9 are pro-angiogen

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… Similarly, the CD44-binding peptide P6 (which binds to the hemopexin domain of MMP-9) impairs the adhesion and migration of CLL cells [ 187 ] ( Table 2 ). These peptides have not yet been tested in Phase I trials on patients with CLL. … Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia B cell survival through its hemopexin domain Cancer Cell 2010 17 160 172 10.1016/j.ccr.2009.12.044 20159608 51. Bauvois B. Nguyen-Khac F. Merle-Béral H. Susin S.A. …

Неожиданное возрождение в отсутствие матричной металопротеины 7.

В множестве склерозов (MS) приток иммунных клеток в центральную нервную систему приводит к обезвоживанию мозга, зрительного нерва и спинного мозга. По мере того как MS прогрессирует, воспоминание становится все более неэффективным, что делает нейронные аксоны уязвимыми для дегенерации и приводит к постоянной неврологической инвалидности. При хронических поражениях MS аберрантная аккумуляция молекул внеклеточной матрицы (ECM), включая фибронектин и гиалуронан, ухудшает олигодендроцитную дифференциацию клеточных клеток, что ведет к сбоям в ремилинации. Таким образом, устранение ингибиторских УХМ

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… In MS, one MMP of interest is MMP7, a particularly powerful metalloproteinase that lacks a classical hemopexin‐like C‐terminal domain common to other MMPs (Baragi et al.  1994 ). …

Daratumumab combined with anti-CD20 therapy in pediatric and adult refractory idiopathic nephrotic syndrome: single-center experience.

BACKGROUND: Refractory idiopathic nephrotic syndrome (INS), in native kidneys or post-transplant, represents a major therapeutic challenge due to its high risk of progressing to end-stage renal disease. Patients often resist anti-CD20 therapy and require prolonged apheresis. Daratumumab, an anti-CD38 monoclonal antibody targeting plasma cells, has demonstrated promising efficacy in case reports when combined with anti-CD20, but evidence remains limited. METHODS: We conducted a single-center retrospective study including four patients (two pediatric, two adult, including one renal transplant)

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… The pathophysiology of INS involves podocyte injury secondary to dysregulated immune mechanisms, including circulating permeability factors such as soluble urokinase plasminogen activator receptor (suPAR), cardiotrophin-like cytokine-1, soluble CD40 ligand, IL-13, hemopexin, angiopoietin-like 4, and, …

Cardiovascular Biomarkers in Cardio-Oncology: Antineoplastic Drug Cardiotoxicity and Beyond.

Serum biomarkers represent a reproducible, sensitive, minimally invasive and inexpensive method to explore possible adverse cardiovascular effects of antineoplastic treatments. They are useful tools in risk stratification, the early detection of cardiotoxicity and the follow-up and prognostic assessment of cancer patients. In this literature review, we aim at describing the current state of knowledge on the meaning and the usefulness of cardiovascular biomarkers in patients with cancer; analyzing the intricate relationship between cancer and cardiovascular disease (especially HF) and how this

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… sFlt)-1, soluble ST2 (sST2), CK-MB, topoisomerase II α gene (TOP2A), cardiac myosin light chain 1 (cMLC-1), vascular endothelial growth factor (VEGF), placental growth factor (PIGF), procollagen-derived type-I C-terminal-propeptide (PICP), epicardial adipose tissue (EAT) volume, circulating bilirubin, hemopexin …

Iron in the Tumor Microenvironment-Connecting the Dots.

Iron metabolism and tumor biology are intimately linked. Iron facilitates the production of oxygen radicals, which may either result in iron-induced cell death, ferroptosis, or contribute to mutagenicity and malignant transformation. Once transformed, malignant cells require high amounts of iron for proliferation. In addition, iron has multiple regulatory effects on the immune system, thus affecting tumor surveillance by immune cells. For these reasons, inconsiderate iron supplementation in cancer patients has the potential of worsening disease course and outcome. On the other hand, chronic im

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… In addition, free Hb and heme are cleared from the circulation in complex with the plasma proteins haptoglobin and hemopexin, respectively ( 210 , 211 ). …

TAM-ing the CIA-Tumor-Associated Macrophages and Their Potential Role in Unintended Side Effects of Therapeutics for Cancer-Induced Anemia.

Cancer-induced anemia (CIA) is a common consequence of neoplasia and has a multifactorial pathophysiology. The immune response and tumor treatment, both intended to primarily target malignant cells, also affect erythropoiesis in the bone marrow. In parallel, immune activation inevitably induces the iron-regulatory hormone hepcidin to direct iron fluxes away from erythroid progenitors and into compartments of the mononuclear phagocyte system. Moreover, many inflammatory mediators inhibit the synthesis of erythropoietin, which is essential for stimulation and differentiation of erythroid progeni

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… CD91, on the other hand, binds heme-hemopexin complexes. Subsequently, intracellular heme is degraded by heme oxygenase-1 (HO1) and detoxified to bilirubin. When HO1’s enzymatic capacity is overwhelmed, and heme starts to accumulate within cells, free heme activates the NLRP3 inflammasome ( 177 ). …

Field-Deployable Treatments For Leishmaniasis: Intrinsic Challenges, Recent Developments and Next Steps.

Leishmaniasis is a neglected tropical disease endemic primarily to low- and middle-income countries, for which there has been inadequate development of affordable, safe, and efficacious therapies. Clinical manifestations of leishmaniasis range from self-healing skin lesions to lethal visceral infection with chances of relapse. Although treatments are available, secondary effects limit their use outside the clinic and negatively impact the quality of life of patients in endemic areas. Other non-medicinal treatments, such as thermotherapies, are limited to use in patients with cutaneous leishman

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… 185 Corroborating this with macrophage function for their important role in iron storage and recycling of senescent red blood cells (RBCs), macrophages ingest senescent RBCs, harvest a larger amount of iron, and facilitate iron breakdown into cytosolic heme which is then used by HMOX1 and binds to hemopexin …

Chemokines and their receptors in oral squamous cell carcinoma: mechanisms, clinical significance, and therapeutic implications.

Chemokines, a category of cytokines exhibiting chemotactic properties, have been thoroughly investigated as targets in cancer treatment in recent decades. In oral squamous cell carcinoma (OSCC), a prevalent and high-risk malignancy of the head and neck, chemokines interact with their specific receptors to initiate downstream signaling pathways. This signaling influences not only tumor cell proliferation, migration, invasion, and metastasis of oral cancer cells but also angiogenesis and vascular maturation. Furthermore, they modulate the tumor microenvironment (TME), which consists of diverse c

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… These proteolytic enzymes, secreted by both normal and cancer cells, consist of a prodomain, a catalytic region, a hinge region, and a hemopexin domain ( 141 ). Chemokines contribute to OSCC development by promoting MMP expression. …

Potential Targeting Mechanisms for Bone-Directed Therapies.

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. Howe

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… A study stated that the hemopexin-like domain is a preferential site of Ca 2+ binding, and hydroxyapatite has this site to bind these ions with four Asp carboxylate groups. …

Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.

This review underscores the dynamic role of the extracellular matrix (ECM) in regulating cellular behavior and maintaining tissue homeostasis, highlighting its pivotal involvement in aging, calcification, and cancer diseases. In healthy tissues, controlled ECM remodeling provides essential biochemical and mechanical cues, but dysregulation (driven by chronic inflammation, cellular senescence, and altered intercellular communication) leads to fibrosis, calcification, and the creation of a pro-tumorigenic microenvironment. Senescent cells contribute to these changes through senescence-associated

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… Their hemopexin domain is necessary for cleaving intact collagen, while the catalytic domain processes non-collagen substrates. These enzymes are important for ECM remodeling, tissue repair, and homeostasis, but their dysregulation is linked to arthritis, fibrosis, and cancer 331 . … It lacks a conventional signal sequence, hemopexin-like repeats, and typical MPP subclass features. Instead, it contains cysteine-rich immunoglobulin-like domains and functions as a type II membrane protein 424 . MMP-23 is predominantly expressed in reproductive tissues. …

ISEV2020 Резюме

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… Remarkably, we detected several proteins (including a fragment of hemopexin) and miRNAs (mir-210) that could be responsible for the proangiogenic and beneficial function of H-CD34Exo. We have also demonstrated that removal of surface proteins diminished the pro-angiogenic function of CD34Exo. …

Abstract

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ISEV2021 Abstract Book

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Р

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Абстрактный сборник ISEV2022.

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Резюме книги: ISEV2017.

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… Moreover, purified heme bound to annexin-A5 with relatively high affinity in vitro , as demonstrated using absorbance shift, autofluorescence quenching and plasmon surface resonance assays, with human serum albumin and hemopexin in competition tests. …

Резюме книги для 27th Конгресс Европейской ассоциации гематологии

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