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PRMT5: An Emerging Target for Pancreatic Adenocarcinoma.

The overall survival of pancreatic ductal adenocarcinoma (PDAC) remains poor and its incidence is rising. Targetable mutations in PDAC are rare, thus novel therapeutic approaches are needed. Protein arginine methyltransferase 5 (PRMT5) overexpression is associated with worse survival and inhibition of PRMT5 results in decreased cancer growth across multiple cancers, including PDAC. Emerging evidence also suggests that altered RNA processing is a driver in PDAC tumorigenesis and creates a partial dependency on this process. PRMT5 inhibition induces altered splicing and this vulnerability can be

Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).

Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑

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… In intestinal radiation fibrosis, irradiation drives mucosal myofibroblasts to secrete CCL11, which recruits eosinophils and accelerates fibrotic progression ( 104 ). … These changes induce fibroblast to myofibroblast differentiation, increase extracellular matrix deposition and contribute to radiation-induced pulmonary fibrosis ( 195 - 197 ). Macrophage-derived CCL22 is selectively upregulated in rat models of radiation pneumonitis ( 198 ). …

Cancer in the Adolescent and Young Adults (AYA) and Children: A Comprehensive Analysis of the Epidemiology and Psychosocial Morbidity in the Indian Population.

Bhupesh GuleriaAims Adolescent and young adults (AYAs), children with cancer, and their guardians have unique psychosocial morbidities adversely effecting quality of life (QOL). This is measurable using patented tools. We analyzed epidemiological and clinicopathological patterns of solid organ cancers in this subgroup. We also assessed psychosocial morbidity and changes in QOL faced by them. Methods All patients aged 2 to 39 years, newly diagnosed with cancer from April 2017 to March 2019 were included. Clinical history, diagnosis, staging, treatment, outcomes, and follow-up were recorded. The

Another Weapon against Cancer and Metastasis: Physical-Activity-Dependent Effects on Adiposity and Adipokines.

Physically active behavior has been associated with a reduced risk of developing certain types of cancer and improved psychological conditions for patients by reducing anxiety and depression, in turn improving the quality of life of cancer patients. On the other hand, the correlations between inactivity, sedentary behavior, and overweight and obesity with the risk of development and progression of various cancers are well studied, mainly in middle-aged and elderly subjects. In this article, we have revised the evidence on the effects of physical activity on the expression and release of the ad

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… In obesity, WAT is enriched in myofibroblasts that deposit a stiff matrix and cause fibrosis (i.e., desmoplasia) [ 29 ], a condition that resembles the tumor microenvironment [ 30 ]. … Myofibroblasts also express vascular endothelial growth factor (VEGF), which stimulates intra-tumor angiogenesis [ 32 ]. By inducing hormones and myokines and counteracting adiposity accumulation, PA limits the risk of cancer development and progression. …

Development and validation of a model for the early prediction of progression from essential thrombocythemia to post-essential thrombocythemia myelofibrosis: a multicentre retrospective study.

BACKGROUND: Essential thrombocythemia (ET), a myeloproliferative neoplasm (MPN), has a substantial risk of evolving into post-essential thrombocythemia myelofibrosis (post-ET MF). This study aims to establish a prediction nomogram for early prediction of post-ET MF in ET patients. METHODS: The training cohort comprised 558 patients from 8 haematology centres between January 1, 2010, and May 1, 2023, while the external validation cohort consisted of 165 patients from 6 additional haematology centres between January 1, 2010, and May 1, 2023. Univariable and multivariable Cox regression analysis

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… Inflammation-induced myelofibrosis involves excessive fibrotic tissue production by myofibroblasts, leading to impaired normal haematopoiesis and increased cytokine release, further promoting clonal expansion. 2 Recent research has identified several serum interleukins that reflect in vivo inflammation …

Nifuroxazide induces the apoptosis of human non‑small cell lung cancer cells through the endoplasmic reticulum stress PERK signaling pathway.

The aim of the present study was to investigate the molecular mechanism of nifuroxazide (NFZ) in the induction of apoptosis of NCI-H1299 human non-small cell lung cancer (NSCLC) cells through the reactive oxygen species (ROS)/Ca2+/protein kinase R-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-DNA damage inducible transcript 3 (CHOP) signaling pathway. Morphological changes of cells were observed by microscopy, and the apoptosis and intracellular ROS levels of cells were observed by inverted fluorescence microscopy. Cell viability after the addition of the PERK inhibitor, GSK26

Calcium Phosphate Ceramics Can Prevent Bisphosphonate-Related Osteonecrosis of the Jaw.

Bisphosphonate-associated osteonecrosis of the jaw (BRONJ), a post-surgical non-healing wound condition, is one of the most common side effects in patients treated with nitrogen-containing bisphosphonates. Its physiopathology has been related with suppression of bone turnover, of soft tissue healing and infection. Biphasic calcium phosphates (BCP) are used as a drug delivery vehicle and as a bone substitute in surgical wounds. Due to their capacity to adsorb zoledronate, it was hypothesized these compounds might have a protective effect on the soft tissues in BRONJ wounds. To address this hypo

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… Fibroblasts and myofibroblasts in wound healing Clin. Cosmet. Investig. Dermatol. 2014 7 301 10.2147/CCID.S50046 25395868 PMC4226391 32. Otto S. Hafner S. Mast G. Tischer T. Volkmer E. Schieker M. Stürzenbaum S.R. von Tresckow E. Kolk A. Ehrenfeld M. …

Roles of Steroids in Preventing Esophageal Stricture after Endoscopic Resection.

Background and purposesEndoscopic resection has been worldwide recognized as a treatment strategy for early esophageal lesions. The occurrence of esophageal stricture after endoscopic resection will reduce the quality of life of patients. This study will evaluate the efficacy and safety of steroids in the prevention of esophageal stricture after endoscopic resection and the influence of different steroid administration methods.MethodsIn the relevant literature database, literature from 2008 to 2018 is retrieved by using preset keywords, the search results are carefully screened, and the conclu

Mesenchymal stem cells in cancer therapy; the art of harnessing a foe to a friend.

For a long time, mesenchymal stem cells (MSCs) were discussed only as stem cells which could give rise to different types of cells. However, when it became clear that their presence in the tumor microenvironment (TME) was like a green light for tumorigenesis, they emerged from the ashes. This review was arranged to provide a comprehensive and precise description of MSCs' role in regulating tumorigenesis and to discuss the dark and the bright sides of cancer treatment strategies using MSCs. To gather the details about MSCs, we made an intensive literature review using keywords, including MSCs,

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… A study reported that MSCs-derived α-smooth muscle actin-positive myofibroblast-like cells prolonged the survival of CSCs in pancreatic cancers through activating the Notch signaling pathway, suggestive of the importance of MSCs in the regulation of cancer metastasis ( 72 ). … Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer cell. 2011;19:257–272. doi: 10.1016/j.ccr.2011.01.020. 62. Fotia C, Massa A, Boriani F, Baldini N, Granchi D. …

Bisphosphonate- and disumab-related gingival disorders: case analysis from the U.S. Food and Drug Administration Adverse Event Reporting System.

Prior research has indicated that bisphosphonates (BPs) can improve periodontal disease because of their anti-osteoporosis properties. In vitro studies have shown that BPs induce cytotoxicity, inhibit wound healing, and thus affect periodontal disease. Denosumab and BPs have alternative indications. BP and denosumab are not known to correlate with gingival disorders. We assessed such a relationship by applying Bayesian and nonproportional analyses to data in the US FDA Adverse Event Reporting System (FAERS) database. The study analyzed BPs and denosumab-reported incidents with preferred terms

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… N-BPs in particular have been found to inhibit the activity of transforming growth factor β (TGF-β) ( 23 ), which is an important factor in the differentiation of fibroblasts into myofibroblasts and thus the promotion of wound healing, cell migration, viability, and proliferation ( 22 ). …

Osteolytic Breast Cancer Causes Skeletal Muscle Weakness in an Immunocompetent Syngeneic Mouse Model.

Muscle weakness and cachexia are significant paraneoplastic syndromes of many advanced cancers. Osteolytic bone metastases are common in advanced breast cancer and are a major contributor to decreased survival, performance, and quality of life for patients. Pathologic fracture caused by osteolytic cancer in bone (OCIB) leads to a significant (32%) increased risk of death compared to patients without fracture. Since muscle weakness is linked to risk of falls which are a major cause of fracture, we have investigated skeletal muscle response to OCIB. Here, we show that a syngeneic mouse model of

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… Crit Rev Oncol Hematol ( 2011 ) 80 ( 3 ): 347 – 68 . 10.1016/j.critrevonc.2011.01.004 21288735 22 Bondi CD Manickam N Lee DY Block K Gorin Y Abboud HE NAD(P)H oxidase mediates TGF-beta1-induced activation of kidney myofibroblasts . …

Keyword Index for Volume 90

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Immunologic tumor microenvironment modulators for turning cold tumors hot.

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment (TME). Hot tumors, characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors (ICIs), stand in stark contrast to cold tumors, which lack immune infiltration and remain resistant to therapy. To overcome immune evasion mechanisms employed by tumor cells, novel immunologic modulators have emerged, particularly ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein

Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy.

BackgroundDegenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expressi

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… 20117302 10.1016/j.jhsa.2009.10.021 51 Usman MA Nakasa T Shoji T The effect of administration of double stranded MicroRNA-210 on acceleration of Achilles tendon healing in a rat model J Orthop Sci 2015 20 3 538 546 25753838 10.1007/s00776-015-0709-5 52 Tomasek JJ Gabbiani G Hinz B Chaponnier C Brown RA Myofibroblasts …

Cancer immunity and immunotherapy beyond COVID-19.

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… Dominguez CX Muller S Keerthivasan S Single-cell RNA sequencing reveals stromal evolution into LRRC15(+) myofibroblasts as a determinant of patient response to cancer immunotherapy Cancer Discov 2020 10 232 253 10.1158/2159-8290.CD-19-0644 31699795 34. …

Thalidomide Suppresses Angiogenesis Through the Signal Transducer and Activator of Transcription 3/SP4 Signaling Pathway in the Peritoneal Membrane.

Peritoneal angiogenesis is the key pathophysiological factor that limits peritoneal ultrafiltration during peritoneal dialysis (PD) in uremic patients. Thalidomide has been confirmed to inhibit angiogenesis by inhibiting the secretion of vascular endothelial growth factor (VEGF), but the exact mechanism by which thalidomide inhibits vascular proliferation during PD is still unclear. Here, the objective of the present study was to investigate whether the reduction in VEGF production by human peritoneal mesothelial cells (HPMCs) was controlled by thalidomide. Stimulation of HPMCs with IL-6 in co

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… Thalidomide treatment significantly decreased submesothelial thickening and angiogenesis and reduced the number of cells expressing PCNA and VEGF, myofibroblasts, and TGF-β-positive cells ( Zhang et al., 2008 ; Arai et al., 2011 ). …

Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment.

Systemic sclerosis (SSc, scleroderma) is a severe disease characterized by peripheral microcirculation abnormalities manifesting with Raynaud's phenomenon, nailfold videocapillaroscopic (NVC) changes, and even ischemic digital ulcers (DUs) that are often refractory to treatments. In the wake of previously described associations between the circulating levels of soluble junctional adhesion molecules (sJAMs) and SSc clinical features, here, we measured sJAM-A and sJAM-C levels by enzyme-linked immunosorbent assay in serum samples from a large case series of 110 SSc patients and 85 healthy contro

Evolving Paradigms in Chronic Graft-Versus-Host Disease: From Global Immunosuppression to Precision Targeted and Cell-Based Therapies.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment for a range of medical conditions. However, the procedure carries with it a significant risk of chronic graft-versus-host disease (cGVHD), which can have a considerable impact on patients’ quality of life and clinical outcomes. In recent years, there has been a marked shift in treatment strategies for this condition, with greater emphasis being placed on novel targeted therapies and cell therapies that target specific pathways. This shift in approach signifies a more profound comprehension of the pa

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… This process enhances α-SMA expression and transdifferentiates fibroblasts into myofibroblasts [ 36 , 37 ]. … Inhibition of the RhoA-ROCK2-MRTF axis has been demonstrated to prevent fibroblast-to-α-SMA+ myofibroblast transdifferentiation and reduce TGF-β and PDGF release. This, in turn, has been shown to reverse collagen deposition and fibrosis in target organs such as the skin and lungs. …

Chimeric antigen receptor T cell therapy for the treatment of systemic rheumatic diseases: a comprehensive review of recent literature.

Systemic rheumatoid diseases (SRDs) are autoimmune and inflammatory disorders that affect multiple organ systems, impacting patients' quality of life, and survival rates. Standard treatment requires continuous drug therapy and immunosuppression. Chimeric antigen receptor (CAR) T cell therapy has the potential to target and eliminate pathologically activated immune cells and re-establish tolerance in organs affected by dysregulated immunity, making them a promising treatment option for autoimmune diseases. In autoimmune diseases, CAR T cells have the advantage of being able to kill B cells effe

Gene editing in cancer therapy: overcoming drug resistance and enhancing precision medicine.

The CRISPR system has revolutionized cancer gene therapy, offering unparalleled precision in genetic manipulation for targeted oncogene disruption, mutation correction, and immune system modulation. This breakthrough tool has demonstrated remarkable potential in overcoming drug resistance, enhancing chemotherapy sensitivity, and improving immunotherapy strategies such as CRISPR-engineered CAR-T cells. Additionally, oncolytic virus-mediated CRISPR delivery has emerged as a novel approach for tumor-specific gene editing, minimizing off-target effects. The rapid transition of CRISPR-based cancer