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Sclerosing diseases of the skin.

Sclerosing skin diseases comprise a group of distinct dermatological conditions characterized by fibrotic changes that may severely impair patients' quality of life. These conditions often present with cutaneous manifestations and, in some cases, may extend to extracutaneous tissues, potentially resulting in significant morbidity and mortality. This review explores the current understanding of the four most prevalent sclerosing skin diseases - localized scleroderma (morphea), systemic sclerosis (SSc), scleromyxedema, and scleredema adultorum of Buschke - as well as sclerotic conditions induced

Impact of physical exercise in cancer survivors during and after antineoplastic treatments.

Cancer patients experience symptoms and adverse effects of treatments that may last even after the end of treatments. Exercise is a safe, non-pharmacological and cost-effective therapy that can provide several health benefits in cancer patient and survivors, reducing cancer symptoms and cancer treatment side effects. The purpose of this review is to describe how the physical exercise is capable to reduce cancer symptoms and cancer treatment side effects. We realized a pragmatic classification of symptoms, dividing them into physical, psychological and psycho-physical aspects. For each symptom

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… The primary lymphedema has a congenital origin (absence or malformation of lymphatic vessels). The secondary lymphedema has an infective or iatrogenic origin, which can be surgical (because of the removal or damage of lymph nodes) or related to radiation therapy because of the lymph nodes fibrosis. … Manual lymphatic drainage consist in slow, very light repetitive circular massages done in a specific sequence to facilitate the removal of retained interstitial proteins, redirect fluid to lymphatic vessels, stimulate lymph flow and promote the development of accessory lymph pathways [ 97 ]. …

Emerging Nanotherapeutic Approaches to Overcome Drug Resistance in Cancers with Update on Clinical Trials.

A key issue with modern cancer treatments is the emergence of resistance to conventional chemotherapy and molecularly targeted medicines. Cancer nanotherapeutics were created in order to overcome the inherent limitations of traditional chemotherapeutics. Over the last few decades, cancer nanotherapeutics provided unparalleled opportunities to understand and overcome drug resistance through clinical assessment of rationally designed nanoparticulate delivery systems. In this context, various design strategies such as passive targeting, active targeting, nano-drug, and multimodal nano-drug combin

Adhesion molecules in multiple myeloma oncogenesis and targeted therapy.

Every day we march closer to finding the cure for multiple myeloma. The myeloma cells inflict their damage through specialized cellular meshwork and cytokines system. Implicit in these interactions are cellular adhesion molecules and their regulators which include but are not limited to integrins and syndecan-1/CD138, immunoglobulin superfamily cell adhesion molecules, such as CD44, cadherins such as N-cadherin, and selectins, such as E-selectin. Several adhesion molecules are respectively involved in myelomagenesis such as in the transition from the precursor disorder monoclonal gammopathy of

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… Further, since inflammation of various levels has often been associated with tumor development, and ICAM-1 expression is up-regulated in lymphatic vessels during inflammation, interaction between MAC-1 and ICAM-1 expressed on DCs and inflamed lymphatic endothelium, respectively, may lead to decreased …

Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.

Bone marrow is the primary site of blood cell production in adults and serves as the source of osteoblasts and osteoclasts that maintain bone homeostasis. The medullary microenvironment is also involved in malignancy, providing a fertile soil for the growth of blood cancers or solid tumors metastasizing to bone. The cellular composition of the bone marrow is highly complex, consisting of hematopoietic stem and progenitor cells, maturing blood cells, skeletal stem cells, osteoblasts, mesenchymal stromal cells, adipocytes, endothelial cells, lymphatic endothelial cells, perivascular cells, and n

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… In addition to this extensive blood vessel network, recent evidence shows that the bone and bone marrow also contain lymphatic vessels ( Biswas et al., 2023 ). … Lymphatic vessels in bone support regeneration after injury. Cell. 2023;186(2):382–397 e24. doi: 10.1016/j.cell.2022.12.031. Bloedjes T.A., et al. Metabolic effects of recurrent genetic aberrations in multiple myeloma. Cancers. 2021;13(3) doi: 10.3390/cancers13030396. …

Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives.

Cancer immunotherapy is a type of treatment that harnesses the power of the immune systems of patients to target cancer cells with better precision compared to traditional chemotherapy. Several lines of treatment have been approved by the US Food and Drug Administration (FDA) and have led to remarkable success in the treatment of solid tumors, such as melanoma and small-cell lung cancer. These immunotherapies include checkpoint inhibitors, cytokines, and vaccines, while the chimeric antigen receptor (CAR) T-cell treatment has shown better responses in hematological malignancies. Despite these

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… Tumor-Associated Lymphatic Vessels Upregulate PDL1 to Inhibit T-Cell Activation Front. Immunol. 2017 8 66 10.3389/fimmu.2017.00066 28217128 PMC5289955 87. Hu K. Babapoor-Farrokhran S. Rodrigues M. Deshpande M. Puchner B. Kashiwabuchi F. Hassan S.J. Asnaghi L. Handa J.T. Merbs S. …

Liposomal Drug Delivery Systems and Anticancer Drugs.

Cancer is a life-threatening disease contributing to ~3.4 million deaths worldwide. There are various causes of cancer, such as smoking, being overweight or obese, intake of processed meat, radiation, family history, stress, environmental factors, and chance. The first-line treatment of cancer is the surgical removal of solid tumours, radiation therapy, and chemotherapy. The systemic administration of the free drug is considered to be the main clinical failure of chemotherapy in cancer treatment, as limited drug concentration reaches the tumour site. Most of the active pharmaceutical ingredien

Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predic

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… The mechanism of action of HSP90α was revealed during in vitro and in vivo experiments: the protein interacts with the LRP1 receptor located on the endothelial cells of lymphatic vessels, which leads to activation of the AKT pathway and increased secretion of CXCL8. … This, in turn, stimulates the growth of lymphatic vessels [ 25 ]. …

Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response

Biological and Clinical Aspects of Metastatic Spinal Tumors.

Spine metastases are a common life-threatening complication of advanced-stage malignancies and often result in poor prognosis. Symptomatic spine metastases develop in the course of about 10% of malignant neoplasms. Therefore, it is essential for contemporary medicine to understand metastatic processes in order to find appropriate, targeted therapeutic options. Thanks to continuous research, there appears more and more detailed knowledge about cancer and metastasis, but these transformations are extremely complicated, e.g., due to the complexity of reactions, the variety of places where they oc

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… Another essential step in the process of metastasis is the entrance of neoplastic cells into blood or lymphatic vessels through which they reach even remotely located organs [ 20 ]. …

Malignant obstruction of the inferior vena cava: clinical experience with the self-expanding Sinus-XL stent system.

PURPOSE: To evaluate the technical and clinical outcome of Sinus-XL stent placement in patients with malignant obstruction syndrome of the inferior vena cava. METHODS: Between October 2010 and January 2021, 21 patients with different malignant primary disease causing inferior vena cava obstruction were treated with Sinus-XL stent implantation. Procedural data, technical and clinical outcome parameters were retrospectively analyzed. RESULTS: Technical success was 100%. Analysis of available manometry data revealed a significant reduction of the mean translesional pressure gradient following t

Musculoskeletal Organs-on-Chips: An Emerging Platform for Studying the Nanotechnology-Biology Interface.

Nanotechnology-based approaches are promising for the treatment of musculoskeletal (MSK) disorders, which present significant clinical burdens and challenges, but their clinical translation requires a deep understanding of the complex interplay between nanotechnology and MSK biology. Organ-on-a-chip (OoC) systems have emerged as an innovative and versatile microphysiological platform to replicate the dynamics of tissue microenvironment for studying nanotechnology-biology interactions. This review first covers recent advances and applications of MSK OoCs and their ability to mimic the biophysic

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… Among the three prevalent cartilage types, hyaline cartilage is the most common and often referred to as articular cartilage due to its coverage of bone extremities. [ 51 ] Unlike its connective tissue counterparts, articular cartilage has no lymphatic vessels, nerves, or vascular networks. … It comprises an endothelial layer consisting of macrophages and fibroblasts, and a submembranous stratum housing blood and lymphatic vessels embedded within a collagen‐rich ECM. [ 53 ] The functions of the synovium are manifold, including preserving a nonadherent tissue surface, providing lubrication …

Progress of Cancer Nanotechnology as Diagnostics, Therapeutics, and Theranostics Nanomedicine: Preclinical Promise and Translational Challenges.

Early detection, right therapeutic intervention, and simultaneous effectiveness mapping are considered the critical factors in successful cancer therapy. Nevertheless, these factors experience the limitations of conventional cancer diagnostics and therapeutics delivery approaches. Along with providing the targeted therapeutics delivery, advances in nanomedicines have allowed the combination of therapy and diagnostics in a single system (called cancer theranostics). This paper discusses the progress in the pre-clinical and clinical development of therapeutics, diagnostics, and theranostics canc

Comprehensive review of targeted therapy for colorectal cancer.

Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world and was responsible for nearly 881,000 cancer-related deaths in 2018. Surgery and chemotherapy have long been the first choices for cancer patients. However, the prognosis of CRC has never been satisfying, especially for patients with metastatic lesions. Targeted therapy is a new optional approach that has successfully prolonged overall survival for CRC patients. Following successes with the anti-EGFR (epidermal growth factor receptor) agent cetuximab and the anti-angiogenesis agent bevacizumab, new agents

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… VEGFR-3, activated by VEGF-C and VEGF-D, contributes relatively independently to lymphatic vessel formation. 170 , 171 Activated VEGFR-3 mediates the differentiation, migration, proliferation and survival of lymphatic endothelial cells by activating the RAS/MAPK/ERK pathway and the PI3K–AKT/PKB pathway … . 169 – 171 Although the VEGFR-3 expression level in tumor cells remains controversial, high levels of VEGF-C and VEGF-D have been observed in tumors with lymphatic metastasis, which is considered a potential explanation for cancer migration through lymphatic vessels. 172 VEGF levels and VEGFR activity …

Engineering precision nanoparticles for drug delivery.

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-

Unlocking the potential of tumor-targeting peptides in precision oncology.

Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy, which is often plagued by poor selectivity, off-target effects, and drug resistance. Among the various targeting agents in development, peptides stand out for their unique advantages, including minimal immunogenicity, high tissue penetration, and ease of modification. Their small size, specificity, and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively. Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery, improvi

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… A tumor-homing peptide with a targeting specificity related to lymphatic vessels . Nat Med . 2002 ; 8 ( 7 ): 751 – 5 . doi: 10.1038/nm720 ; 12053175 105. Papo N , Seger D , Makovitzki A , Kalchenko V , Eshhar Z , Degani H , et al . …

Cardiac Involvement in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Cardiac involvement of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is recognized extremely rarely. In addition, most CLL/SLL patients with heart infiltration are asymptomatic. In this review, we present the results of a literature search for English language articles concerning CLL/SLL or Richter transformation with symptomatic cardiac involvement. In total, 18 well-described cases with CLL/SLL and heart infiltration were identified. Only three patients were not diagnosed with CLL/SLL before the cardiac manifestation. In other patients, cardiac CLL/SLL was diagnosed betwe

Vasculopathy as a mechanical barrier to cancer spread: Clinical evidence and a rheology-based model in lung cancer and other solid tumors.

Metastatic dissemination in lung cancer (LC) and other solid tumors is influenced not only by tumor-intrinsic biology and immune-inflammatory responses, but also by the physical properties of the vascular system through which circulating tumor cells (CTCs) migrate. Peripheral arterial disease (PAD), particularly when associated with aneurysmal dilation, is frequent among long-term smokers and is characterized by chronic vascular inflammation and altered hemodynamics. We hypothesized that PAD-related vascular remodeling and rheological alterations may influence tumor metastatic capacity. Throug

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… Once activated, cancer cell invasiveness relies on the induction of blood and lymphatic vessels, and on the cell ability to extravasate and reach distant organs [ 12 ]. …

Chemokines: humble yet mighty players in the tumour microenvironment.

Chemokines are tiny chemotactic cytokines which play a crucial role in pathophysiology by maintaining homeostasis and inflammation. Their role in the tumour microenvironment is very much puzzling because of both pro- and anti-tumourigenic effects. Chemokines have gained much attention today, since it has been recognized that they are game changers in the TME via controlling immune cell recruitment, angiogenesis, metastasis, tumour growth and drug resistance. In this review, we are exploring the role of several chemokines and their receptors in the TME with special focus on immune cell recruitm

Transformative Impact of Nanocarrier-Mediated Drug Delivery: Overcoming Biological Barriers and Expanding Therapeutic Horizons.

Advancing therapeutic progress is centered on developing drug delivery systems (DDS) that control therapeutic molecule release, ensuring precise targeting and optimal concentrations. Targeted DDS enhances treatment efficacy and minimizes off-target effects, but struggles with drug degradation. Over the last three decades, nanopharmaceuticals have evolved from laboratory concepts into clinical products, highlighting the profound impact of nanotechnology in medicine. Despite advancements, the effective delivery of therapeutics remains challenging because of biological barriers. Nanocarriers offe

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… Additionally, the TME promotes the lymphatic vessels development through the secretion of VEGF‐D and VEGF‐C by cancer, stromal, and immune cells, a process termed tumor‐associated lymphangiogenesis. … However, lymphatic vessel development within the TME is associated with poor prognosis, as it facilitates metastatic spread to distant organs ( Figure 6 A ). [ 173 , 174 ] Figure 6 Vascular normalization mechanisms, associated signaling pathways, and the role of drug‐loaded NPs. …