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Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells.

Tumor angiogenesis is widely recognized as one of the "hallmarks of cancer". Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic

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… LH39 is an antibody directed against an epitope of the basement membrane of normal capillaries and small venules; LH39 is more predominantly expressed in non-angiogenic (pre-existing) compared to angiogenic tumor vessels [ 120 ] and therefore might be a useful biomarker to discriminate between the two …

Highlighting recent achievements to advance more effective cancer immunotherapy.

From 17 to 19th October 2024, the XXI Italian Network for Bio-Immunotherapy of Tumors Meeting (NIBIT) took place in Palermo, in the marvelous historical location of Teatro Politeama, under the auspices of the Italian Association of Medical Oncology (AIOM), Italian Association of Cancer Research (AIRC), Fondazione Pezcoller, Italian Alliance against Cancer (ACC), Italian Lymphoma Foundation (FIL), Grazia Focacci Foundation and Melagioco Foundation. The conference covered a spectrum of topics ranging from target discovery to therapeutic advances in immuno-oncology, bringing world-renowned expert

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… She hypothesized that by changing tumor vessels into high endothelial venules (HEV), an anti-tumor immunity enabling T cell infiltration and TLS formation may be induced. …

Клинические 7 Тесла магнитный резонансный снимок: воздействие и ценность пациента в неврологических расстройствах.

Магнитный резонансный снимок (MRI) является краеугольным камнем неинвазивной диагностики и контроля за лечением, особенно в случае заболеваний центральной нервной системы. Хотя 1.5- и 3 Тесла (Т) сильные стороны поля остаются клиническим стандартом, появление 7 МРТ представляет собой преобразующий шаг вперед, предлагающий высокое пространственное разрешение, контраст и чувствительность для визуализации нейроанатомии, метаболизма и функции. Последние нововведения, включая параллельную передачу и глубокую реконструкцию на основе накопленного опыта, позволили решить многие ранее возникшие техниче

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… MS is characterized by perivenous pathology marked by the accumulation of inflammatory cells surrounding venules. These small veins can best be visualized in the center of MS lesions on susceptibility‐weighted sequences. …

Bleeding Propensity in Waldenström Macroglobulinemia: Potential Causes and Evaluation.

Waldenström macroglobulinemia (WM) is a rare, incurable, low-grade, B cell lymphoma. Symptomatic disease commonly results from marrow or organ infiltration and hyperviscosity secondary to immunoglobulin M paraprotein, manifesting as anemia, bleeding and neurological symptoms among others. The causes of the bleeding phenotype in WM are complex and involve several intersecting mechanisms. Evidence of defects in platelet function is lacking in the literature, but factors impacting platelet function and coagulation pathways such as acquired von Willebrand factor syndrome, hyperviscosity, abnormal

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… red blood cells, resulting in an agglutinating effect and contributing to increased viscosity. 43 Healthy individuals have around 1.5 g/L of IgM, of which 80% is intravascular, 44 and hyperviscosity emerges when IgM levels exceed 50 to 60 g/L. 44 Hyperviscosity causes the physical tearing of small venules …

Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View.

Hepatocellular Carcinoma (HCC) is a pressing health concern, demanding a deep understanding of various mediators' roles in its development for therapeutic progress. Notably, interleukin-6 (IL-6) has taken center stage in investigations due to its intricate and context-dependent functions. This review delves into the dual nature of IL-6 in HCC, exploring its seemingly contradictory roles as both a promoter and an inhibitor of disease progression. We dissect the pro-tumorigenic effects of IL-6, including its impact on tumor growth, angiogenesis, and metastasis. Concurrently, we examine its anti-

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… This impact extends to structures such as high endothelial venules, which facilitate the entry of naive and memory T cells into lymph nodes and the endothelium of blood vessels within tumors. …

Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease.

Graft versus host disease (GVHD) is the major non-relapse complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, GVHD occurs in roughly half of patients following this therapy and can induce severe life-threatening side effects and premature mortality. The pathophysiology of GVHD is driven by alloreactive donor T cells that induce a proinflammatory environment to cause pathological damage in the skin, gastrointestinal (GI) tract, lung, and liver during the acute phase of this disease. Recent work has demonstrated that the GI tract is a pivotal ta

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… When expressed on T lymphocytes, α4β7 integrin licenses cells to bind to mucosal addressin cell adhesion molecule (MAdCAM), which is chiefly expressed on high endothelial venules of mucosal lymphoid organs as well as intestinal lamina propria ( 80 ). …

I

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… This transendothelial migration (diapedesis) of leukocytes takes place in postcapillary venules by a number of adhesive interactions between adhesive molecules on the surfaces of leukocytes and endothelium. …

Cryoglobulinemia: An update on classification, pathophysiology, clinical presentation, and management.

Cryoglobulinemia (CG) is defined by the presence of serum immunoglobulins that precipitate below 37°C and redissolve upon rewarming. It is classified into three types based on immunoglobulin composition. Type I, a rare form, involves monoclonal IgM or IgG and is linked to lymphoproliferative disorders. Types II and III are known as mixed CG (MC): Type II consists of polyclonal IgG and monoclonal IgM with rheumatoid factor (RF) activity, whereas Type III includes polyclonal IgG and polyclonal IgM with RF activity. MC is predominantly associated with hepatitis C virus (HCV) infection and involve

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… This latter condition is known as cryoglobulinemic vasculitis (CV) and predominantly affects capillaries, venules, or arterioles [ 12 , 13 ]. When cryoglobulins aggregate, they obstruct blood flow to joints, muscles, and organs. …

Neutrophilic and eosinophilic dermatoses associated with hematological malignancy.

Cutaneous manifestations of hematologic malignancy represent both a clinical challenge for the treating physician and a pathophysiological model for advancing the knowledge on individual neoplasms. Indeed, a growing body of evidence supports the concept of recurrent molecular defects associating with specific clinical features, as best exemplified by VEXAS. Herein neutrophilic and eosinophilic dermatoses of potential interest for both hematologists and dermatologists will be reviewed, including subcorneal pustular dermatosis-type IgA pemphigus, neutrophilic eccrine hidradenitis, Sweet's syndro

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… Immune complex deposition occurring in post-capillary venules as a result of infections, hematologic or autoimmune diseases, may then lead to the production of key cytokines, such as IL-8, setting the inflammatory process in motion, similarly to other ND ( 51 ). …

Livedoid vasculopathy: A multidisciplinary clinical approach to diagnosis and management.

Livedoid vasculopathy (LV) is a rare, chronic, and occlusive disease of the veins supplying the upper parts of the skin. The pathogenesis of the disease is not precisely understood, and its attacks are often unpredictable but tend to worsen during the summer. LV affects women more often. This increased risk for LV in women might be related to sex-specific physiological conditions, such as pregnancy, or a higher incidence of LV-associated conditions, such as connective tissue diseases, hypercoagulable states, and venous stasis in women. The typical clinical appearance of LV consists of three ma

Эпидемиология, патология и патогенез MS: терапевтические последствия.

Множественный склероз (MS) является хроническим и потенциально деактивирующим воспалительным заболеванием центральной нервной системы (CNS). МS, как правило, характеризуется повторяющимися и самоограниченными эпизодами неврологической дисфункции, которые происходят непредсказуемо и часто приводят к множественным повреждениям тканей в рамках CNS. В настоящее время женщины страдают в два-три раза чаще, чем мужчины, хотя это, возможно, не произошло в предыдущие периоды времени. Известно, что патогенез MS связан как с критическими генетическими, так и с экологическими механизмами. Тем не менее, по

Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.

Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells to recognize and attack tumor cells. T-cells are isolated from patients and modified to target tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma by targeting CD-19 and B-cell maturation antigens. Bi-specific chimeric antigen receptors may contribute to mitigating tumor anti

Терапевтическое применение иммунобиологии в аутоиммунных и воспаленных заболеваниях.

Иммунобиологика или биологическая экспертиза революционизировали терапевтическую парадигму аутоиммунных и подстрекательских заболеваний путем выборочного целеопределения и модуляции дисрегулированных иммунных путей. По сравнению с обычными широкоспектральными иммунопрепрессантами биологика обеспечивает более конкретный и основанный на механизмах рациональный подход, зачастую связанный с повышением эффективности и сокращением неблагоприятных явлений. В этом обзоре содержится всеобъемлющий обзор репертуара терапевтической биологики, механизмов их действий, важнейших клинических испытаний и клини

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… trafficking of immune cells into the gut as well as their retention and pro-inflammatory activity within the intestinal mucosa. α4β7 is a key mediator of leucocyte homing to the gastrointestinal tract via interactions with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on high endothelial venules … Vedolizumab (VDZ) Vedolizumab (MLN0002) is a humanized IgG1 monoclonal antibody that selectively targets the α4β7 integrin, thereby inhibiting its interaction with MAdCAM-1 (mucosal addressin cell adhesion molecule-1) expressed on gut endothelial venules. …

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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… in PAH lungs adopt a classic conformation of tertiary lymphoid organs (TLOs), characterised by a central B-cell follicle that contains follicular dendritic cells, and a well-segregated CD4 + T-cell peripheral zone embedded in a network of fibroblastic reticular cells and supplied by high-endothelial venules …

The Past, Present, and Future of Clinically Applied Chimeric Antigen Receptor-T-Cell Therapy.

Immunotherapy represents the fourth pillar of cancer therapy after surgery, chemotherapy, and radiation. Chimeric antigen receptor (CAR)-T-cell therapy is an artificial immune cell therapy applied in clinical practice and is currently indicated for hematological malignancies, with cluster of differentiation 19 (CD19) as its target molecule. In this review, we discuss the past, present, and future of CAR-T-cell therapy. First, we summarize the various clinical trials that were conducted before the clinical application of CD19-targeted CAR-T-cell therapies began. Second, we discuss the accumulat

Unraveling the mechanisms of bone diseases: targeting dendritic cells in osteoimmunology for internal homeostasis balance.

Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types, which need to precisely mediated for effective healing post-damage. The concept of osteoimmunology emphasizes the extensive and intricate crosstalk between the bone and the immune system. Despite the significant advancements in understanding osteoimmunology, the precise role of dendritic cells (DCs) in this field remains under investigation. As key antigen-presenting cells, DCs are critical in orchestrating adaptive immune responses and maintaining tissue homeostasis. Recent researches have fur

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… Bone marrow-resident dendritic cells (BMDCs) BMDCs consisted of a small population of bone marrow cells (1%–2%), which organized into perivascular clusters enveloping sinusoid and venules without direct contacting the vessel walls indicated by two-photon intravital microscopy. 33 In addition, F4/80 …

Metastatic Breast Cancer: Review of Emerging Nanotherapeutics.

Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed b

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… Elongated metastatic cells round up and form cytoplasmic protrusions to expand the surrounding vascular wall, before or during the process of extravasation, with this process happening exclusively in capillaries and post-capillary venules that lack smooth muscle cells [ 76 , 78 ]. …

Blood Vessels and Peripheral Nerves as Key Players in Cancer Progression and Therapy Resistance.

Cancer cells continuously interact with the tumor microenvironment (TME), a heterogeneous milieu that surrounds the tumor mass and impinges on its phenotype. Among the components of the TME, blood vessels and peripheral nerves have been extensively studied in recent years for their prominent role in tumor development from tumor initiation. Cancer cells were shown to actively promote their own vascularization and innervation through the processes of angiogenesis and axonogenesis. Indeed, sprouting vessels and axons deliver several factors needed by cancer cells to survive and proliferate, inclu

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… Human Solid Tumors Contain High Endothelial Venules: Association with T- and B-Lymphocyte Infiltration and Favorable Prognosis in Breast Cancer. Cancer Res. 2011;71:5678–5687. doi: 10.1158/0008-5472.CAN-11-0431. 41. Schepers K., Campbell T.B., Passegué E. …

Integumentary System

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… Thus induction of the immune response does not normally occur within the skin itself but rather in the skin-draining lymph nodes. • The dermal perivascular unit consists of the mast cells, monocytes and macrophages, tissue dendritic cells, and T cells situated around postcapillary venules. … Vasculitis Vasculitis is characterized by inflammation targeting the walls of venules or arterioles, resulting in at least partial destruction of the vessel wall, sometimes with fibrin deposition ( Fig. 6-15 ). …

Optimal Treatment of Retinal Vein Occlusion: An Updated Canadian Review and Recommendations.

Retinal vein occlusion (RVO) represents a heterogeneous group of disorders that remains the second most common retinal vascular disease and can be associated with vision loss. RVO confers a substantial burden of illness that affects patients, caregivers, medical systems, and physicians. Complications of RVO - including cystoid macular edema, macular ischemia, and neovascularization sequelae - may result in severe visual morbidity and blindness. Canadian expert consensus recommendations on the optimal treatment of patients with RVO were published in 2015. Since that time, advances in diagnosis