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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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… Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 2017;214:579–596. doi: 10.1084/jem.20162024. 22. Biffi G., Oni T.E., Spielman B., Hao Y., Elyada E., Park Y., Preall J., Tuveson D.A. …

CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.

The acronym for the CCN family was recently revised to represent "cellular communication network". These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN prote

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… High levels of CCN5 hinder adipogenic differentiation as they dedifferentiate 3T3-L1 adipose cells into pluripotent myofibroblasts expressing α-SMA (Grünberg et al. 2014 ). …

Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgen

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… Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer J. Exp. Med. 2017 214 579 596 10.1084/jem.20162024 28232471 PMC5339682 57. Chen C.T. Chen Y.C. Yamaguchi H. Hung M.C. …

Expert consensus on resection of chest wall tumors and chest wall reconstruction.

Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients. Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forw

Rare Diseases of the Nose, the Paranasal Sinuses, and the Anterior Skull Base.

Due to their low incidence and thus resulting limited diagnostic criteria as well as therapeutic options, rare diseases of the nose, the paranasal sinuses, and the anterior skull base are a significant challenge. The value as of which a disease has to be considered as rare amounts to a maximum of 5 patients per 10 000 people. Within these diseases, however, there are extreme differences. Some rare or orphan diseases like for example the inverted papilloma belong to regularly diagnosed and treated diseases of larger departments of oto-rhino-laryngology whereas other rare diseases and malformati

Sodium-glucose cotransporter 2 inhibitors and the cancer patient: from diabetes to cardioprotection and beyond.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class initially designed and approved for treatment of diabetes mellitus, have been shown to exert pleiotropic metabolic and direct cardioprotective and nephroprotective effects that extend beyond their glucose-lowering action. These properties prompted their use in two frequently intertwined conditions, heart failure and chronic kidney disease. Their unique mechanism of action makes SGLT2i an attractive option also to lower the rate of cardiac events and improve overall survival of oncological patients with preexisting cardiovascu

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

Recent Trends in anti-tumor mechanisms and molecular targets of celastrol.

Celastrol, a compound derived from traditional Chinese medicine, has therapeutic effects and has been used to treat inflammation-related diseases, cancer, cardiovascular diseases, and neurodegenerative diseases. However, current reviews lack a comprehensive and systematic summary of the anti-tumor mechanisms and molecular targets of celastrol. For this reason, this paper reviews the anticancer properties of celastrol and the molecular mechanisms underlying its anticancer effects. This paper primarily focuses on the mechanism of action of celastrol in terms of inhibition of cell proliferation a

Potential Adverse Effects of Dexamethasone Therapy on COVID-19 Patients: Review and Recommendations.

In the context of the coronavirus disease 2019 (COVID-19) pandemic, the global healthcare community has raced to find effective therapeutic agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, dexamethasone is the first and an important therapeutic to significantly reduce the risk of death in COVID-19 patients with severe disease. Due to powerful anti-inflammatory and immunosuppressive effects, dexamethasone could attenuate SARS-CoV-2-induced uncontrolled cytokine storm, severe acute respiratory distress syndrome and lung injury. Nevertheless, dexamethasone tre

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… Fibrosis and renin-angiotensin-aldosterone system Circulation 1991 83 1849 1865 1828192 10.1161/01.cir.83.6.1849 107. van den Borne SW Diez J Blankesteijn WM Verjans J Hofstra L Narula J Myocardial remodeling after infarction: the role of myofibroblasts Nat Rev Cardiol 2010 7 30 37 19949426 10.1038/ …

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools.

Chronic kidney disease (CKD) is an increasing health burden (affecting approximately 13.4% of the population). Currently, no curative treatment options are available and treatment is focused on limiting the disease progression. The accumulation of senescent cells has been implicated in the development of kidney fibrosis by limiting tissue rejuvenation and through the secretion of pro-fibrotic and pro-inflammatory mediators termed as the senescence-associated secretory phenotype. The clearance of senescent cells in aging models results in improved kidney function, which shows promise for the op

HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the

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… Transforming growth factor β-1 (TGF-β1) mediates the transformation of fibroblasts into myofibroblasts, regulates tissue fibrosis, and increases the synthesis of extracellular matrix components. …

Uncommon Factors Leading to Nephrotic Syndrome.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransfe

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… Then, the damaged tubular epithelial cells can transform into myofibroblasts, which lead to fibrosis and significant destruction of the renal structure. …

Galectins in the Pathogenesis of Common Retinal Disease.

Diseases of the retina are major causes of visual impairment and blindness in developed countries and, due to an ageing population, their prevalence is continually rising. The lack of effective therapies and the limitations of those currently in use highlight the importance of continued research into the pathogenesis of these diseases. Vascular endothelial growth factor (VEGF) plays a major role in driving vascular dysfunction in retinal disease and has therefore become a key therapeutic target. Recent evidence also points to a potentially similarly important role of galectins, a family of β-g

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… Its cause is an abnormal growth of tissues on the inner retinal surface at the macular area, with fibroblasts and myofibroblasts found in overlaying fibrotic patches ( Wang, et al., 2016 ). …

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

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… Tumour angiogenesis MSCs promote tumour angiogenesis either by their differentiation into fibroblasts, pericytes, and myofibroblasts or by producing specific growth factors [23] . …

Targeting urological cancers with CAR-T cell therapy: current landscape and future directions.

BACKGROUND: Urological cancers, including renal, bladder, and prostate cancers, are among the most prevalent solid tumors. The success of chimeric antigen receptor (CAR)-T cell therapy in hematologic malignancies has spurred its exploration for treating urological cancers. MAIN BODY: In the past decade, preclinical studies have demonstrated promising antitumor activity of CAR-T cells against urological cancers. Meanwhile, multiple clinical trials are currently underway to evaluate their safety and efficacy. However, significant challenges impede the efficacy of CAR-T cell therapy in urological

The Potential and Prospects of Marine Drugs in Intervening Nerve-Tumor Crosstalk.

The bidirectional crosstalk between the nervous system and tumors has emerged as a transformative new frontier in both precision oncotherapy and mechanism-driven cancer pain management. Marine natural products with inherent neuroactive properties exhibit unparalleled intervention advantages for targeting this complex pathophysiological axis. Herein, we systematically and prospectively dissect the multi-layered bidirectional communication between the nervous system and malignancies, comprehensively summarize the pivotal contributions of marine-derived bioactive molecules to advances in neurosci

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… Myofibroblasts Induce Neuroplasticity to Promote Pancreatic Inflammation and Cancer Progression. Cancer Discov. 2026;16:1014–1034. doi: 10.1158/2159-8290.cd-25-1337. 6. Zhang S., Yuan L., Lin P., Yang G., Zhou X., Xu J., Wu M., Huang Y. …

High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges.

Vitamin C, also known as ascorbic acid, has sparked controversy since it first emerged as a potential anti-cancer agent. However, an increasing number of preclinical studies have demonstrated that high-dose vitamin C exhibits selective anti-tumor effects, including "pro-oxidative cytotoxicity", "anti-cancer epigenetic regulation", and "immune modulation". Consequently, vitamin C has reemerged as a promising anti-cancer therapy in the form of high-dose administration. Advancements in pharmacokinetic research have facilitated the development of clinical trials. Early clinical studies across vari

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… Studies have shown that it effectively inhibits the transformation of fibroblasts into myofibroblasts, thereby mitigating radiation-induced pulmonary fibrosis. …

Ginsenoside-Mediated Ferroptosis Regulation: Bidirectional Effects and Therapeutic Potential in Diseases.

Notably, certain ginsenoside components exhibit distinct bidirectional and context-dependent regulatory effects on ferroptosis depending on the disease setting. In aberrantly proliferating or activated cells, ginsenosides function as ferroptosis inducers, whereas in damaged quiescent cells of normal tissues, they act as ferroptosis inhibitors. The pro-ferroptotic effect is predominantly observed in cells characterized by abnormal proliferation or activation, such as cancer cells and activated hepatic stellate cells in liver fibrosis. In this context, ginsenosides modulate key iron metabolism p

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… Liver Fibrosis In the uninjured liver, HSCs occupy the Space of Disse as quiescent cells specialized for vitamin A storage; conversely, persistent parenchymal damage drives their transdifferentiation into myofibroblasts, marked by de novo α-smooth muscle actin (α-SMA) expression, migration to injured …

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

Role of TRP Channels in Cancer-Induced Bone Pain.

The burden of cancer is growing in almost every country. Bone metastases significantly affect the prognosis and lead to an increase in mortality and morbidity. The management of cancer-induced bone pain (CIBP) still shows various unmet needs. Opioid use is burdened by a number of possible side effects. Moreover, recent progresses in cancer treatment significantly increased the life expectancy of cancer patients, even those with metastatic disease. In this narrative review, we reported the main findings regarding TRP channel function in cancer pain models. TRP cation channels play a key role in

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… Activation of TRPA1 in Bladder Suburothelial Myofibroblasts Counteracts TGF-β1-Induced Fibrotic Changes. Int. J. Mol. Sci. 2023;24:9501. doi: 10.3390/ijms24119501. 193. …