Результаты поиска

Hypoxia within the glioblastoma tumor microenvironment: a master saboteur of novel treatments.

Glioblastoma (GBM) tumors are the most aggressive primary brain tumors in adults that, despite maximum treatment, carry a dismal prognosis. GBM tumors exhibit tissue hypoxia, which promotes tumor aggressiveness and maintenance of glioma stem cells and creates an overall immunosuppressive landscape. This article reviews how hypoxic conditions overlap with inflammatory responses, favoring the proliferation of immunosuppressive cells and inhibiting cytotoxic T cell development. Immunotherapies, including vaccines, immune checkpoint inhibitors, and CAR-T cell therapy, represent promising avenues f

Совпадение в полном тексте источника
… Glioma stem cells themselves also generate novel vasculature by transforming themselves into pericytes or endothelial cells ( 42 , 43 ). This pro-angiogenesis drive is supported by the tumor’s inherent metabolic, inflammatory, and hypoxic conditions. … The BBB is comprised of astrocytes, endothelial cells, and tight junctions by pericyte feet, which together tightly regulate the transfer of molecules between the blood and brain parenchyma ( 45 ). …

Immunohistochemical expression of CD57 in different histopathological grades of oral squamous cell carcinoma.

Background and aimIn general, the natural killer (NK) cells are considered to represent the innate immune system and act as the vital effector of lymphocytes. Natural killer cells (NK) cells target and destroy tumour-causing cells. The purpose of this study is to analyse the immunohistochemical expression of CD57 in different histopathological grades of Oral Squamous cell Carcinoma (OSCC).Materials and methodsThirty archival blocks were selected from the Department of Oral and Maxillofacial Pathology and Oral Microbiology, Vinayaka Mission's Sankarachariyar Dental College, Salem comprising 10

Совпадение в полном тексте источника
… The microenvironment, commonly referred to as the tumour stroma, is needed for nutritional support and for the removal of waste products.[ 8 ] The tumour microenvironment (TME) consists of, endothelial cells, pericytes, mesenchymal cells, adipocytes, and innate and adaptive immune cells.[ 9 ] The tumour …

Длинная и извилистая дорога: гомеостатические и беспорядочные микроэкологические ниши: обзор описательной части.

Микроэкологические ниши Haematopoiet были охарактеризованы как "приемники" крови и иммунной системы. Эти ниши меняются во время онтгении, при этом костный мозг становится доминирующим местом гематопоисиса в послеродовой жизни в стабильных условиях. Для определения структуры и функции различных микроэкологических ниш гематопоиета необходимо четко определить конкретные подмножества гематопоиетических стеблей и потомковых клеток во время офгении и понять их временной внешний вид и анатомическое позиционирование. Различные гематопоиетические и негематопоиетические клетки способствуют появлению гем

Совпадение в полном тексте источника
… SCA-1 + PDGFR - a(CD140a) + ) as pericytes, have recently been reviewed. 29 , 141 , 184 These will not be further discussed in detail here, except to say that Soliman et al. 185 argue against the pericyte description for certain MSC subsets by virtue of their transcriptomic profiles and presence outside … blood vessel basement membranes and their location near pericytes in capillaries, small blood vessels and in the adventitial layer of large blood vessels. …

Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females.

Most studies on ketosis have focused on short-term effects, male athletes, or weight loss. Hereby, we studied the effects of short-term ketosis suppression in healthy women on long-standing ketosis. Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) maintaining nutritional ketosis (NK) for > 1 year (3.9 years ± 2.3) underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Adherence to each phase was confirmed with daily capillary D-beta-hydroxybutyrate (BHB) tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; an

Совпадение в полном тексте источника
… Pericytes are supportive cells which wrap around blood vessels, serving as multilineage progenitor cells, and are essential for the development of new blood vessels [ 117 ]. … Insulin stimulates pericytes to increase their production of VEGF, which, in turn, stimulates endothelial cells to grow and proliferate, facilitating angiogenesis [ 118 ]. The lower levels of insulin in the NK phases likely account for the lower levels of VEGF. …

The Bone Marrow Microenvironment Mechanisms in Acute Myeloid Leukemia.

Bone marrow (BM) is a highly complex tissue that provides important regulatory signals to orchestrate hematopoiesis. Resident and transient cells occupy and interact with some well characterized niches to produce molecular and cellular mechanisms that interfere with differentiation, migration, survival, and proliferation in this microenvironment. The acute myeloid leukemia (AML), the most common and severe hematological neoplasm in adults, arises and develop in the BM. The osteoblastic, vascular, and reticular niches provide surface co-receptors, soluble factors, cytokines, and chemokines that

Совпадение в полном тексте источника
… The inner layer of the vessel is composed of endothelial cells (ECs), which are covered by perivascular cells called pericytes. … Ang-1, a ligand also derived from pericytes, inhibits the apoptosis of ECs, thereby promoting the regulation of HSCs ( Dimmeler and Zeiher 2000 ). Another molecule with a potential role in angiogenesis is endomucin-1 (EMCN). …

Monoclonal Antibodies-Anchored Quantum Dots-Based Delivery Strategies for Glioblastoma Treatment: Challenges and Applications.

Treatment of glioblastoma multiforme (GBM) has been a great challenge before medical fraternity since last century owing to a median survival of less than 15 months, despite of intensive therapy. Neurosurgeries, intense chemotherapy, advanced radiotherapy, and targeted therapies have bought some extension to the life of GBM patients. Combination and targeted therapies could bring a concrete approach to tackle the complexities of GBM treatment. Monoclonal antibodies (mAbs) have already proved their potential, owing to their high affinity and target-specificity, as a promising cancer immunothera

Совпадение в полном тексте источника
… An adult BBB consists of brain endothelial cells, basal membrane, pericytes, and end-feet. 56 , 57 These intricately linked elements constitute a strong structure that considerably reduces the permeability of drug substances such as antitumor drugs. 58 The brain capillaries are surrounded by astrocytes … , pericytes, microglia, and neuronal processes, all of which are intimately related. 59 In brain, the capillary endothelial cells have specialized barrier properties to ensure the homeostasis and protection of the CNS. 60 In addition, BBB emerges as a great challenge in delivering the mAbs-anchored …

UFMTrack, "Недоходный миграционный трекер", позволяющий проанализировать весь многоэтапный каскад экстравазии иммунных клеток через барьер кровеносного мозга в микрофлюидовых устройствах.

Эндотелиальный барьер кровеносного мозга (БДБ) строго контролирует оборот иммунных клеток в центральную нервную систему (КНС). В таких нейро-воспалительных заболеваниях, как множественный склероз, этот жесткий контроль, однако, нарушается, что приводит к инфильтрации иммунных клеток в CNS. Разработка моделей BBB in vitro в сочетании с микрофлюидовыми устройствами способствовала более глубокому пониманию клеточных и молекулярных механизмов посредничества многоэтапной экстравазии Т-клеток по всему BBB. Одним из основных узких мест в этих исследованиях in vitro является отсутствие надежного и авт

Совпадение в полном тексте источника
… While, in the microfluidic device used in the present study, the migration of T cells below the pMBMEC monolayer may not be biologically relevant, this analysis option will be valuable for future studies involving multilayer in vitro BBB models that include the vascular basement membrane in addition to pericytes … Finally, the possibility of quantifying the motility parameters of the transmigrated T cells enables future studies involving multilayer in vitro BBB models that include the vascular basement membrane in addition to mural cells such as pericytes and astrocytes mimicking the entire neurovascular unit. …

New Directions in the Study and Treatment of Metastatic Cancer.

Traditional cancer therapy has relied on a strictly cytotoxic approach that views non-metastatic and metastatic tumor cells as identical in terms of molecular biology and sensitivity to therapeutic intervention. Mounting evidence suggests that, in fact, non-metastatic and metastatic tumor cells differ in key characteristics that could explain the capacity of the metastatic cells to not only escape the primary organ but also to survive while in the circulation and to colonize a distant organ. Here, we lay out a framework for a new multi-pronged therapeutic approach. This approach involves modif

Совпадение в полном тексте источника
… (E) Fraction of vessels with pericyte coverage. The difference in the fraction of vessels positive for alpha-smooth muscle actin (alpha-SMA) in patient 2 was identified as an outlier by the Extreme Studentized Deviate test. … Bone provides a unique environment that is characterized by dynamic interplay between multiple cell types including mesenchymal cells (osteocytes, osteoblasts, and adipocytes), hematopoietic cells (immune cells and osteoclasts), endothelial cells, and pericytes ( 105 ). …

The potential of mesenchymal stem cells in the management of radiation enteropathy.

Although radiotherapy is effective in managing abdominal and pelvic malignant tumors, radiation enteropathy is still unavoidable. This disease severely affects the quality of life of cancer patients due to some refractory lesions, such as intestinal ischemia, mucositis, ulcer, necrosis or even perforation. Current drugs or prevailing therapies are committed to alleviating the symptoms induced by above lesions. But the efficacies achieved by these interventions are still not satisfactory, because the milieus for tissue regeneration are not distinctly improved. In recent years, regenerative ther

Совпадение в полном тексте источника
… , several events mediated this homing process, such as CXCR1/2-CXCL8, CXCR4-CXCL12, CX 3 CR1-fractalkine, CCR7-CCL21 and ICAM-1/VCAM-1. 77 , 83 , 84 , 85 Upon these molecular bindings, MSCs first adhere to the endothelium, forming a defensive barrier against pathogens together with the pre-existing pericytes … Towards in situ tissue repair: human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2 J Cell Biochem 2007 101 135 146 17295203 10.1002/jcb.21172 Paguet-Fifield S Schlüter H Li A Aitken T Gangatirkar P Blashki D A role for pericytes …

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

Совпадение в полном тексте источника
… Interestingly, they found stromal cell populations inside the solid tumor microenvironment including osteoblasts, endothelium, pericytes and osteoclasts. These data indicate the importance of bone resident cells in tumor growth of bone metastasis [57] . … Human-derived osteoblast-like cells and pericyte-like cells induce distinct metastatic phenotypes in primary breast cancer cells Exp. Biol. Med. (Maywood) 246 2021 971 985 10.1177/1535370220971599 33210551 PMC8024509 33 Krishnan V. Shuman L.A. Sosnoski D.M. Dhurjati R. Vogler E.A. Mastro A.M. …

Targeting the Post-Irradiation Tumor Microenvironment in Glioblastoma via Inhibition of CXCL12.

Radiotherapy is a mainstay in glioblastoma therapy as it not only directly targets tumor cells but also depletes the tumor microvasculature. The resulting intra-tumoral hypoxia initiates a chain of events that ultimately leads to re-vascularization, immunosuppression and, ultimately, tumor-regrowth. The key component of this cascade is overexpression of the CXC-motive chemokine ligand 12 (CXCL12), formerly known as stromal-cell derived factor 1 (SDF-1). We here review the role of CXCL12 in recruitment of pro-vasculogenic and immunosuppressive cells and give an overview on future and current dr

Совпадение в полном тексте источника
… Notably, CXCL12-CXCR4 interactions target GBM stem cells to endothelial cells in the perivascular niche where they may be induced to differentiate into pericytes by transforming growth factor (TGF)-β1 [ 109 ]. … Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 2013;153:139–152. doi: 10.1016/j.cell.2013.02.021. 110. Lee J.H., Lee J.E., Kahng J.Y., Kim S.H., Park J.S., Yoon S.J., Um J.Y., Kim W.K., Lee J.K., Park J., et al. …

Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice.

Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cel

Совпадение в полном тексте источника
… Although MSCs are usually isolated from the bone marrow, adipose tissue, and cord blood, they can also be obtained from other tissues such as smooth, skeletal and cardiac muscle, spleen, liver, pancreas, lung, testes, menstrual blood, periosteum, dermis, pericytes, trabecular bone, placenta, amniotic … Tumour angiogenesis MSCs promote tumour angiogenesis either by their differentiation into fibroblasts, pericytes, and myofibroblasts or by producing specific growth factors [23] . …

Роль аполипопротеина Е в нейродегенеративных заболеваниях.

Apolipopetein E (APOE) — белок, широко выраженный в большинстве нейронов центральной нервной системы. Зависящие от APOE изменения эндоцитного пути могут влиять на различные функции. APOE связывается с клеточными рецепторами для доставки липидов и гидрофобными амилоидами β-пептида, регулируя амилоидно-β-агрегирование и расчистку мозга. Было обнаружено несколько изоформов APOE с существенными структурными различиями, которые оказывают влияние на перенос липидов мозга, метаболизм глюкозы, нейрональный сигнал, нейроинфламмацию и митохондриальную функцию. В ходе этого обзора будет обобщена обновлен

Совпадение в полном тексте источника
… that APOE4 is associated with higher plasma total cholesterol and LDL, followed by APOE3 and APOE2. 7 , 8 This is largely attributed to APOE4 preferentially binding to VLDL and APOE3 to HDL. 9 The central nervous system In the central nervous system (CNS), APOE mainly produced by astrocytes (either pericytes …

Фармакологическое ингибирование микроглиального распространения поддерживает целостность барьера крови и мозга в экспериментальном аутоиммунном энцефаломелите.

Дефункция мозга в крови (ББД) является основной характеристикой экспериментального аутоиммунного энцефаломиелита (EAE) — экспериментальной модели множественного склероза (MS). Ранее мы показали, что блокирование микроглиального распространения с использованием GW2580, селективного ингибитора CSF1R (колонический стимулирующий фактор 1 рецептор), снижает прогрессию и остроту заболеваний и предотвращает фазу рецидива. Однако вопрос о том, вызвано ли это воздействием GW2580 на функциональную целостность ББД, не был определен. Таким образом, здесь мы изучаем свойства ББД у крыс во время лечения EAE

Совпадение в полном тексте источника
… The BBB’s integrity relies on components such as tight junction-sealed endothelial cells, pericytes, astrocytic endfeet [ 56 , 57 ], and the endothelial and parenchymal basement membranes [ 41 ]. …

Keyword Index for Volume 111

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Совпадение в полном тексте источника
… carcinoma 2229 PARP 1319 pathological response 470 pathology 918 patient preference 674 patient selection 2156 pazopanib 1909 PD-1 1391 PD2 486 Pdk1 817 pelvic lymph node dissection 213 pelvic lymph node metastasis 112 pemetrexed 220 penectomy 1089 penile cancer 1089 percentiles 2205 pericytes …

Chimeric antigen receptor-based cell therapy for treating urological tumors.

Urological tumors represent a significant global health challenge, with conventional therapies often proving insufficient to control disease progression. Recent breakthroughs in cellular immunotherapy, particularly in chimeric antigen receptor (CAR)-T cell, CAR-natural killer cell, and CAR-macrophage therapies, have demonstrated remarkable potential for treating these malignancies. Ongoing research is actively refining CAR-based strategies to enhance their precision in targeting tumor-associated antigens. This review comprehensively summarizes the applications of CAR cell therapy in the follow

Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact.

Antiangiogenic drugs were the only mainstay of advanced hepatocellular carcinoma (HCC) treatment from 2007 to 2017. However, primary or secondary resistance hampered their efficacy. Primary resistance could be due to different molecular and/or genetic characteristics of HCC and their knowledge would clarify the optimal treatment approach in each patient. Several molecular mechanisms responsible for secondary resistance have been discovered over the last few years; they represent potential targets for new specific drugs. In this light, the advent of checkpoint inhibitors (ICIs) has been a new o

Совпадение в полном тексте источника
… The goal of the anti-angiogenic therapy, in this perspective, is not only to inhibit the vascular system but also to modify the TME, which will be characterized by less hypoxia, less vascular leak, an increase in the number of pericytes along with an increase in CD8 + T cell infiltration and a decrease … In this context of defining the normalization window in experimental models of different tumors, it was found that the signal mediated by the Ang1/Ang2-Tie2 axis is important for the recruitment of pericytes for tumor vessels and that the overexpression of Ang2 may negate the benefit of anti-VEGF therapy …

Vitamin C Transporters and Their Implications in Carcinogenesis.

Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe2+ dependent dioxygenases (2-OGDD), which are involved in active DNA demethylation (TET proteins), the demethylation of histones, and hypoxia processes. Therefore, vitamin C may be engaged in the regulation of gene expression or in a hypoxic state. Hence, vitamin C has acquired great interest for its plausible effects on cancer treatment. Since its conceptualization, the role of vitamin C in cancer t

Совпадение в полном тексте источника
… In line with this research, Parker et al. indicated that the pericytes found in brain microvessels are enriched with SVCT2 transporters, which allows such microvessels to collect ascorbate [ 55 ]. … Ascorbic acid transport in brain microvascular pericytes. Biochem. Biophys. Res. Commun. 2015;458:262–267. doi: 10.1016/j.bbrc.2015.01.096. 56. Rumsey S.C., Kwon O., Xu G.W., Burant C.F., Simpson I., Levine M. Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J. Biol. …

Cellular immunotherapy in melanoma: the next frontier in cancer treatment.

Therapy-resistant melanoma remains a major clinical challenge despite advances with immune checkpoint inhibitors and targeted therapies, as most patients ultimately exhibit primary or acquired resistance and progress through multiple toxic treatment lines with limited durable benefit. This resistance reflects not only T-cell dysfunction but also a profound quantitative deficit of tumor-reactive lymphocytes, compounded by myeloid- and Treg-mediated immunosuppression, impaired antigen presentation, and tumor dedifferentiation programs generating a cold tumor microenvironment. Cellular immunother

Совпадение в полном тексте источника
… safety/MTD) | NCT04897321 IL13Rα2 | IL-13 receptor α2 | Subsets of melanoma (heterogeneous); elevated in some brain mets | Limited normal expression (e.g., testis, smooth muscle, variable) | Recruiting | Phase I (safety/dose) | NCT04119024 CSPG4 | MCSP, HMW-MAA | High and frequent on melanoma cells | Pericytes … Chondroitin sulfate proteoglycan 4 (CSPG4), also referred to as NG2, is frequently expressed on primary and metastatic melanoma and other aggressive tumors, whereas normal expression is largely restricted to pericytes and selected stromal subsets, implying possible vascular off-tumor toxicity [ 128 – …

Bisphosphonate-related osteonecrosis. Application of adipose-derived stem cells in an experimental murine model.

BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw is a pathological condition without effective established treatment and preventive strategies. The aim of this study was to analyse the effect of adipose-derived stem cells (ASC) in an experimental murine model of osteonecrosis. MATERIAL AND METHODS: 38 Wistar rats were injected intraperitoneally with zoledronic acid. After treatment, upper jaw molars were extracted. The animals were randomly assigned to one of two groups. In the control group, saline solution was applied over the alveolar sockets after the tooth extractions. In the

Совпадение в полном тексте источника
… The SVF is a heterogenous population including endothelial cells, pericytes, fibroblasts, preadipocytes, ASCs... ( 25 , 38 ), so they have different properties compared with purified ASCs. …