Normalization of tumor vasculature by imiquimod: proposal for a new anticancer therapeutic indication for a TLR7 agonist.

Imiquimod (IMQ), a drug from aminoquinoline group, is the toll-like receptor 7 (TLR7) agonist. It acts as an immunostimulant and radio-sensitizing agent. IMQ stimulates both innate and adaptive immune response.

Differential Response to Local Stimulator of Interferon Genes Agonist Administration in Tumors with Various Stimulator of Interferon Genes Statuses.

: The stimulator of interferon genes (STING) is currently accepted as a relevant target for anti-cancer therapies. Besides encouraging results showing STING agonist-induced tumor growth inhibition, in some types of tumors the effect is less prominent. We hypothesized that higher STING levels in cancer cells and the possibility of its activation determine a greater anti-cancer response.

Tumor hypoxia unveiled: insights into microenvironment, detection tools and emerging therapies.

Hypoxia is one of the defining characteristics of the tumor microenvironment (TME) in solid cancers. It has a major impact on the growth and spread of malignant cells as well as their resistance to common treatments like radiation and chemotherapy. Here, we explore the complex functions of hypoxia in the TME and investigate its effects on angiogenesis, immunological evasion, and cancer cell metabolism.

Combination of STING agonist with anti-vascular RGD-(KLAKLAK) peptide as a novel anti-tumor therapy.

Immunotherapy is one of the most promising anti-cancer treatment. It involves activating the host's own immune system to eliminate cancer cells. Activation of cGAS-STING pathway is promising therapeutic approach for cancer immunotherapy.

The comparison of adipose-derived stromal cells (ADSCs) delivery method in a murine model of hindlimb ischemia.

Background: Adipose-derived stromal cells (ADSCs) demonstrate ability to promote tissue healing and down-regulate excessive inflammation. ADSCs have been used to treat critical limb ischemia in preclinical and clinical trials, but still, there is little known about their optimal delivery strategy. To date, no direct analysis of different methods of ADSCs delivery has been performed in the hindlimb ischemia model.

Antitumor effect of anti-vascular therapy with STING agonist depends on the tumor microenvironment context.

Introduction: Targeting tumor vasculature is an efficient weapon to fight against cancer; however, activation of alternative pathways to rebuild the disrupted vasculature leads to rapid tumor regrowth. Immunotherapy that exploits host immune cells to elicit and sustain potent antitumor response has emerged as one of the most promising tools for cancer treatment, yet many treatments fail due to developed resistance mechanisms. Therefore, our aim was to examine whether combination of immunotherapy and anti-vascular treatment will succeed in poorly immunogenic, difficult-to-treat melanoma and triple-negative breast tumor models.

The Effect of Radiotherapy on Cell Survival and Inflammatory Cytokine and Chemokine Secretion in a Co-Culture Model of Head and Neck Squamous Cell Carcinoma and Normal Cells.

Radiotherapy (RT) is one of the main treatments for head and neck squamous cell carcinomas (HNSCCs). Unfortunately, radioresistance is observed in many cases of HNSCCs. The effectiveness of RT depends on both the direct effect inducing cell death and the indirect effect of changing the tumor microenvironment (TME).

Novel Local "Off-the-Shelf" Immunotherapy for the Treatment of Myeloma Bone Disease.

Myeloma bone disease (MBD) is one of the major complications in multiple myeloma (MM)-the second most frequent hematologic malignancy. It is characterized by the formation of bone lesions due to the local action of proliferating MM cells, and to date, no effective therapy has been developed. In this study, we propose a novel approach for the local treatment of MBD with a combination of natural killer cells (NKs) and mesenchymal stem cells (MSCs) within a fibrin scaffold, altogether known as FINM.

Prognostic Significance of STING Immunoexpression in Relation to HPV16 Infection in Patients with Squamous Cell Carcinomas of Oral Cavity and Oropharynx.

Infection with HPV16 in cancers of the oral cavity (OCSCC) and oropharynx (OPSCC) is, today, an important etiological and prognostic factor. Patients with HPV-positive OPSCC have a better prognosis than uninfected patients. However, in over 40% of these patients, cancer progression is noticed.

The Complex Composition of Trans-resveratrol, Quercetin, Vitamin E and Selenium Inhibits the Growth of Colorectal Carcinoma.

Background/aim: Numerous studies have demonstrated an anti-cancer action of plant-derived polyphenols. Their action is mainly related to antioxidant, anti-inflammatory, immunomodulatory and inhibitory properties. It is expected that proper composition of nutrition factors with anti-cancer activity may prevent from cancer incidence or inhibit cancer progression.

Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma.

Due to immunosuppressive properties and confirmed tropism towards cancer cells mesenchymal stromal cells (MSC) have been used in many trials. In our study we used these cells as carriers of IL-12 in the treatment of mice with primary and metastatic B16-F10 melanomas. IL-12 has confirmed anti-cancer activity, induces a strong immune response against cancer cells and acts as an anti-angiogenic agent.

The Proper Administration Sequence of Radiotherapy and Anti-Vascular Agent-DMXAA Is Essential to Inhibit the Growth of Melanoma Tumors.

Vascular disrupting agents (VDAs), such as DMXAA, effectively destroy tumor blood vessels and cause the formation of large areas of necrosis in the central parts of the tumors. However, the use of VDAs is associated with hypoxia activation and residues of rim cells on the edge of the tumor that are responsible for tumor regrowth. The aim of the study was to combine DMXAA with radiotherapy (brachytherapy) and find the appropriate administration sequence to obtain the maximum synergistic therapeutic effect.

Selection, Expansion, and Unique Pretreatment of Allogeneic Human Natural Killer Cells with Anti-CD38 Monoclonal Antibody for Efficient Multiple Myeloma Treatment.

Cellular immunotherapy is becoming a new pillar in cancer treatment after recent striking results in different clinical trials with chimeric antigen receptor T cells. However, this innovative therapy is not exempt from challenges such as off-tumor toxicity, tumor recurrence in heterogeneous tumors, and affordability. To surpass these limitations, we exploit the unique anti-tumor characteristics of natural killer (NK) cells.

Electrospun paclitaxel delivery system based on PGCL/PLGA in local therapy combined with brachytherapy.

The local administration of different drugs in anticancer therapy continue to attract attention. Thus, the idea of local delivery of cytostatics from nonwoven-structured polyesters seems to be highly desirable. It could reduce systemic drug levels and provide high local concentration of the chemotherapeutics at the tumor site and contribute to enhance the efficiency of the anticancer therapy.

Effect of Heme Oxygenase-1 on Melanoma Development in Mice-Role of Tumor-Infiltrating Immune Cells.

Objective: Heme oxygenase-1 (HO-1) is a cytoprotective, proangiogenic and anti-inflammatory enzyme that is often upregulated in tumors. Overexpression of HO-1 in melanoma cells leads to enhanced tumor growth, augmented angiogenesis and resistance to anticancer treatment. The effect of HO-1 in host cells on tumor development is, however, hardly known.

Vascular disrupting agents in cancer therapy.

Tumor blood vessel formation is a key process for tumor expansion. Tumor vessels are abnormal and differ from normal vessels in architecture and components. Besides oxygen and nutrients supply, the tumor vessels system, due to its abnormality, is responsible for: hypoxia formation, and metastatic routes.

Adipose tissue-derived stromal cells stimulated macrophages-endothelial cells interactions promote effective ischemic muscle neovascularization.

Neovascularization, the process of new blood vessels formation in response to hypoxia induced signals, is an essential step during wound healing or ischemia repair. It follows as a cascade of consecutive events leading to new blood vessels formation and their subsequent remodeling to a mature and functional state, enabling tissue regeneration. Any disruption in consecutive stages of neovascularization can lead to chronic wounds or impairment of tissue repair.

Brachytherapy in a Single Dose of 10Gy as an "in situ" Vaccination.

Radiotherapy (RT) is one of the major methods of cancer treatment. RT destroys cancer cells, but also affects the tumor microenvironment (TME). The delicate balance between immunomodulation processes in TME is dependent, among other things, on a specific radiation dose.

Author Correction: Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PHLDA1 Does Not Contribute Directly to Heat Shock-Induced Apoptosis of Spermatocytes.

Spermatocytes are among the most heat-sensitive cells and the exposure of testes to heat shock results in their Heat Shock Factor 1 (HSF1)-mediated apoptosis. Several lines of evidence suggest that pleckstrin-homology-like domain family A, member 1 (PHLDA1) plays a role in promoting heat shock-induced cell death in spermatogenic cells, yet its precise physiological role is not well understood. Aiming to elucidate the hypothetical role of PHLDA1 in HSF1-mediated apoptosis of spermatogenic cells we characterized its expression in mouse testes during normal development and after heat shock.

Monitoring of diffusion properties and transverse relaxation time of mouse ischaemic muscle after administration of human mesenchymal stromal cells derived from adipose tissue.

Objectives: Application of non-invasive imaging methods plays an important role in the assessment of cellular therapy effects in peripheral artery disease. The purpose of this work was to evaluate the kinetics of MRI-derived parameters characterizing ischaemic hindlimb muscle after administration of human mesenchymal stromal cells derived from adipose tissue (hADSC) in mice.

Materials And Methods: MRI experiments were performed on a 9.

The effect of culture media on large-scale expansion and characteristic of adipose tissue-derived mesenchymal stromal cells.

Background: Adipose tissue-derived mesenchymal stromal cells (ASCs) have been shown to exhibit some promising properties of their use in regenerative medicine as advanced therapy medicinal products (ATMP). However, different sources of their origin, methods of isolation, and expansion procedures cause the laboratory and clinical results difficult to compare.

Methods: ASCs were isolated from lipoaspirates and cultured in three different medium formulations: αMEM and DMEM as a basal medium supplemented with 10% of human platelet lysate (hPL) and DMEM supplemented with 20% fetal bovine serum (FBS) and bFGF as a gold standard medium.

Tumor Microenvironment as A "Game Changer" in Cancer Radiotherapy.

Radiotherapy (RT), besides cancer cells, also affects the tumor microenvironment (TME): tumor blood vessels and cells of the immune system. It damages endothelial cells and causes radiation-induced inflammation. Damaged vessels inhibit the infiltration of CD8+ T lymphocytes into tumors, and immunosuppressive pathways are activated.

Human ADSC xenograft through IL-6 secretion activates M2 macrophages responsible for the repair of damaged muscle tissue.

Background: Adipose-derived mesenchymal stromal cells (ADSCs) are multipotent stromal cells. The cells secrete a number of cytokines and growth factors and show immunoregulatory and proangiogenic properties. Their properties may be used to repair damaged tissues.

Bioresorbable filomicelles for targeted delivery of betulin derivative - In vitro study.

Filomicelles (worm-like micelles) possess high drug loading capacity and long circulation time in the bloodstream. A novel approach can be filomicelles with folic acid (FA) as a targeting moiety. Folate-drug delivery systems can target FA receptors (FAR) that are overexpressed in several human carcinomas, which can potentially maximize therapeutic efficacy while minimizing side effects.