PO-203 A novel member in the β-catenin destruction complex: may MAPK14/P38α foster new therapeutic approaches in colorectal cancer?

Colorectal cancer (CRC) is a leading cause of cancer-related death. The demand for new therapeutic approaches has increased attention paid toward therapies with high targeting efficiency, improved selectivity and few side effects. Porphyrins are powerful molecules with exceptional properties and multifunctional uses, and their special affinity to cancer cells makes them the ligands par excellence for anticancer drugs. Porphyrin derivatives are used as the most important photosensitizers (PSs) for photodynamic therapy (PDT), which is a promising approach for anticancer treatment. Nevertheless, the lack of solubility and selectivity of the large majority of these macrocycles led to the development of different photosensitizer complexes. In addition, targeting agents or nanoparticles were used to increase the efficiency of these macrocycles for PDT applications. On the other hand, gold tetrapyrrolic macrocycles alone showed very interesting chemotherapeutic activity without PDT. In this review, we discuss the most important porphyrin derivatives, alone or associated with other drugs, which have been found effective against CRC, as we describe their modifications and developments through substitutions and delivery systems.

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The dysbiosis signature of Fusobacterium nucleatum in colorectal cancer-cause or consequences? A systematic review

Cancer Cell International ◽

10.1186/s12935-021-01886-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maryam Ranjbar ◽

Rasoul Salehi ◽

Shaghayegh Haghjooy Javanmard ◽

Laleh Rafiee ◽

Habibollah Faraji ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Genetic Factors ◽

Fusobacterium Nucleatum ◽

Published Data ◽

Structural Components ◽

Epigenetic Factors ◽

Therapeutic Approaches ◽

Mortality And Morbidity ◽

New Therapeutic Approaches

AbstractColorectal cancer (CRC) is the third most common cause of cancer globally and the fourth attributable cause of mortality and morbidity due to cancer. An emerging factor contributing to CRC is the gut microbiota and the cellular changes associated with it. Further insights on this may help in the prevention, diagnosis and new therapeutic approaches to colorectal cancer. In most cases of CRC, genetic factors appear to contribute less to its aetiology than environmental and epigenetic factors; therefore, it may be important to investigate these environmental factors, their effects, and the mechanisms that may contribute to this cancer. The gut microbiota has recently been highlighted as a potential risk factor that may affect the structural components of the tumor microenvironment, as well as free radical and enzymatic metabolites directly, or indirectly. Many studies have reported changes in the gut microbiota of patients with colorectal cancer. What is controversial is whether the cancer is the cause or consequence of the change in the microbiota. There is strong evidence supporting both possibilities. The presence of Fusobacterium nucleatum in human colorectal specimens has been demonstrated by RNA-sequencing. F. nucleatum has been shown to express high levels of virulence factors such as FadA, Fap2 and MORN2 proteins. Our review of the published data suggest that F. nucleatum may be a prognostic biomarker of CRC risk, and hence raises the potential of antibiotic treatment of F. nucleatum for the prevention of CRC.

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The Macrophages-Microbiota Interplay in Colorectal Cancer (CRC)-Related Inflammation: Prognostic and Therapeutic Significance

International Journal of Molecular Sciences ◽

10.3390/ijms21186866 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6866

Author(s):

Silvia Mola ◽

Chiara Pandolfo ◽

Antonio Sica ◽

Chiara Porta

Keyword(s):

Colorectal Cancer ◽

Tumor Development ◽

Prognostic Indicators ◽

Functional Heterogeneity ◽

Therapeutic Approaches ◽

Effector Cells ◽

New Therapeutic Approaches ◽

Cancer Types ◽

Macrophage Subtypes ◽

Main Population

Tumor-associated macrophages (TAMs) are the main population of myeloid cells infiltrating solid tumors and the pivotal orchestrators of cancer-promoting inflammation. However, due to their exceptional plasticity, macrophages can be also key effector cells and powerful activators of adaptive anti-tumor immunity. This functional heterogeneity is emerging in human tumors, colorectal cancer (CRC) in particular, where the dynamic co-existence of different macrophage subtypes influences tumor development, outcome, and response to therapies. Intestinal macrophages are in close interaction with enteric microbiota, which contributes to carcinogenesis and affects treatment outcomes. This interplay may be particularly relevant in CRC, one of the most prevalent and lethal cancer types in the world. Therefore, both macrophages and intestinal microbiota are considered promising prognostic indicators and valuable targets for new therapeutic approaches. Here, we discuss the current understanding of the molecular circuits underlying the interplay between macrophages and microbiota in CRC development, progression, and response to both conventional therapies and immunotherapies.

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Vascular Smooth Muscle Cell Proliferation: Basic Investigations and New Therapeutic Approaches

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646152 ◽

1993 ◽

Vol 70 (01) ◽

pp. 010-016 ◽

Cited By ~ 24

Author(s):

Robert D Rosenberg

Keyword(s):

Cell Proliferation ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Vascular Smooth Muscle Cell ◽

Smooth Muscle Cell Proliferation ◽

Therapeutic Approaches ◽

New Therapeutic Approaches

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New therapeutic approaches for polymyositis and dermatomyositis

Orvosi Hetilap ◽

10.1556/oh.2011.29176 ◽

2011 ◽

Vol 152 (39) ◽

pp. 1552-1559 ◽

Cited By ~ 2

Author(s):

Katalin Dankó ◽

Melinda Vincze

Keyword(s):

Immunosuppressive Agents ◽

Inflammatory Myopathy ◽

Proximal Muscle ◽

Therapeutic Approaches ◽

First Line ◽

New Therapeutic Approaches ◽

Remission Period ◽

Immune Mediated ◽

Systemic Manifestations ◽

Line Of Therapy

Inflammatory myopathies are chronic, immune-mediated diseases characterized with progressive proximal muscle weakness. They encompass a variety of syndromes with protean manifestations. The aims of therapy are to increase muscle strength, prevent the development of contractures, and to manage the systemic manifestations of the disease. This is a complex treatment which requires routine and wide knowledge. The most important task is to recognize the disease and guide the patient to immunologic center. Although the first line of therapy continues to include corticosteroids, there are a multitude of agents available for treating patients with myositis. There are several different immunosuppressive agents which may be applied alone or in combination with each other, as well as an increasing number of novel and exciting biologic agents targeting molecules participating in the pathogenesis of inflammatory myopathy. Physiotherapy and rehabilitation in the remission period may significantly improve the functional outcome of patients with these disorders. Orv. Hetil., 2011, 152, 1552–1559.

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New Aspects of the Epigenetics of Pancreatic Carcinogenesis

Epigenomes ◽

10.3390/epigenomes4030018 ◽

2020 ◽

Vol 4 (3) ◽

pp. 18

Author(s):

Murat Toruner ◽

Martin E. Fernandez-Zapico ◽

Christopher L. Pin

Keyword(s):

Pancreatic Cancer ◽

Dna Methylation ◽

Survival Rate ◽

Epigenetic Mechanisms ◽

Therapeutic Approaches ◽

Cancer Epigenetics ◽

Pancreatic Carcinogenesis ◽

New Therapeutic Approaches ◽

Environmental Events ◽

Underlying Pathogenesis

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA methylation, histone modifications and RNA interference, all of which are altered by changes to the environment. Epigenetic mechanisms are being investigated to clarify the underlying pathogenesis of pancreatic cancer including an increasing number of studies examining the role as possible diagnostic and prognostic biomarkers. These mechanisms also provide targets for promising new therapeutic approaches for this devastating malignancy.

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LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression

Biomedicines ◽

10.3390/biomedicines9020195 ◽

2021 ◽

Vol 9 (2) ◽

pp. 195

Author(s):

Francisca Dias ◽

Cristina Almeida ◽

Ana Luísa Teixeira ◽

Mariana Morais ◽

Rui Medeiros

Keyword(s):

Colorectal Cancer ◽

Amino Acid ◽

Cancer Progression ◽

Cell Metabolism ◽

Tumor Development ◽

Amino Acid Transporters ◽

Epigenetic Alterations ◽

Therapeutic Approaches ◽

Colorectal Cancer Progression ◽

Made In

The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results. In this review we combine a bioinformatic approach with a literature review in order to identify a miRNA profile with the potential to target both LAT1 and ASCT2 with potential to be used as a therapeutic approach against CRC.

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A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

Immuno ◽

10.3390/immuno1030011 ◽

2021 ◽

Vol 1 (3) ◽

pp. 174-193

Author(s):

Jenny Valentina Garmendia ◽

Juan Bautista De Sanctis

Keyword(s):

Nk Cells ◽

Nk Cell ◽

Embryo Implantation ◽

Inflammatory Cells ◽

Cell Physiology ◽

Therapeutic Approaches ◽

Pharmacological Modulation ◽

New Therapeutic Approaches ◽

Pharmacologic Modulation ◽

Inflammatory Burden

NK cells are lymphocytes involved in the innate and adaptative immune response. These cells are located in peripheral blood and tissues with ample functions, from immune vigilant to tolerogenic reactions. In the endometrium, NK cell populations vary depending on age, hormones, and inflammation. When pregnancy occurs, tissue-resident NK cells and conventional NK cells are recruited to protect the fetus, a tolerogenic response. On the contrary, in the inflamed endometrium, various inflammatory cells down-regulate NK tolerance and impair embryo implantation. Therefore, NK cells’ pharmacological modulation is difficult to achieve. Several strategies have been used, from progesterone, lipid emulsions to steroids; the success has not been as expected. However, new therapeutic approaches have been proposed to decrease the endometrial inflammatory burden and increase pregnancy success based on understanding NK cell physiology.

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The Effect of a Polyester Nanofibrous Membrane with a Fibrin-Platelet Lysate Coating on Keratinocytes and Endothelial Cells in a Co-Culture System

Nanomaterials ◽

10.3390/nano11020457 ◽

2021 ◽

Vol 11 (2) ◽

pp. 457

Author(s):

Andreu Blanquer ◽

Jana Musilkova ◽

Elena Filova ◽

Johanka Taborska ◽

Eduard Brynda ◽

...

Keyword(s):

Wound Healing ◽

Endothelial Cells ◽

Chronic Wounds ◽

Human Keratinocytes ◽

Skin Wound ◽

Platelet Lysate ◽

Therapeutic Approaches ◽

Skin Wound Healing ◽

New Therapeutic Approaches ◽

Proliferation And Differentiation

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.

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Regulation of Eosinophilia in Asthma—New Therapeutic Approaches for Asthma Treatment

Cells ◽

10.3390/cells10040817 ◽

2021 ◽

Vol 10 (4) ◽

pp. 817

Author(s):

Ruth P. Cusack ◽

Christiane E. Whetstone ◽

Yanqing Xie ◽

Maral Ranjbar ◽

Gail M. Gauvreau

Keyword(s):

Drug Targets ◽

Airflow Obstruction ◽

Chronic Inflammatory Disease ◽

Therapeutic Approaches ◽

Eosinophilic Asthma ◽

Airway Eosinophilia ◽

Gm Csf ◽

New Therapeutic Approaches ◽

Cellular Apoptosis ◽

Reversible Airflow Obstruction

Asthma is a complex and chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, bronchospasm, and airway eosinophilia. As the pathophysiology of asthma is becoming clearer, the identification of new valuable drug targets is emerging. IL-5 is one of these such targets because it is the major cytokine supporting eosinophilia and is responsible for terminal differentiation of human eosinophils, regulating eosinophil proliferation, differentiation, maturation, migration, and prevention of cellular apoptosis. Blockade of the IL-5 pathway has been shown to be efficacious for the treatment of eosinophilic asthma. However, several other inflammatory pathways have been shown to support eosinophilia, including IL-13, the alarmin cytokines TSLP and IL-33, and the IL-3/5/GM-CSF axis. These and other alternate pathways leading to airway eosinophilia will be described, and the efficacy of therapeutics that have been developed to block these pathways will be evaluated.

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