bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2025–11–09
six papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. METTL14 integrates tumor-derived SAM to drive parabrachial epigenetic rewiring in pancreatic cancer.
  2. The Efficacy and Safety of Beta-blockers and Immune Checkpoint Inhibitors in Patients with Cancer: A Systematic Review and Meta-analysis.
  3. Sodium channel modulation as a therapeutic strategy for chemotherapy-induced peripheral neurotoxicity.
  4. Preoperative MRI prediction and molecular pathway study of perineural invasion in intrahepatic cholangiocarcinoma: Insights from bioinformatics approach.
  5. Case Report: Malignant peripheral nerve sheath tumor of the kidney with a novel granular cell morphology.
  6. Multinodular/Plexiform Schwannoma of the Ankle: A Case Report and Literature Review.
  1. Neuron. 2025 Nov 04. pii: S0896-6273(25)00755-X. [Epub ahead of print]
    METTL14 integrates tumor-derived SAM to drive parabrachial epigenetic rewiring in pancreatic cancer.
    Xiaohua Yang, Xintong Wang, Weicheng Lu, Qingqing Ye, Yongchun Li, Xinyu Ma, Yaqi Ye, Xiangna Guo, Guojun Chen, Wenjun Xin, Ting Xu, Weian Zeng, Jingdun Xie.
      Tumor-neural crosstalk drives cancer progression and neurological symptoms, yet how tumors rewire brain circuits remains unclear. Here, we identified upregulated methyltransferase-like 14 (METTL14) in lateral parabrachial nucleus glutamatergic neurons (LPBNGlu) as a key regulator of pain-depression comorbidity in pancreatic ductal adenocarcinoma (PDAC) mice. METTL14 inhibition reversed PDAC-induced neuronal hyperexcitability and alleviated behavioral deficits. Mechanistically, METTL14 coordinated the tumor-derived S-adenosylmethionine (SAM) to promote N6-methyladenosine (m6A) modification of adrenomedullin (ADM) mRNA, enhancing neuronal hyperactivation and potentiating LPBNGlu projections to the paraventricular thalamus (PVT) and lateral hypothalamus (LH). ADM suppression and chemogenetic or optogenetic silencing of LPBNGlu → PVTGlu/LHGlu circuits significantly mitigated comorbidity. Moreover, elevated circulating SAM in PDAC patients and mice amplifies this pathway. A methionine-restricted diet (MRD) reduced SAM levels, mitigating comorbidity and suppressing tumor growth. Our findings unveil the SAM-METTL14-ADM axis and LPBNGlu → PVTGlu/LHGlu neurocircuits in PDAC-induced brain remodeling, positioning MRD as a promising therapeutic strategy to improve patient outcomes.
    DOI:  https://doi.org/10.1016/j.neuron.2025.10.002
  2. Target Oncol. 2025 Nov 01.
    The Efficacy and Safety of Beta-blockers and Immune Checkpoint Inhibitors in Patients with Cancer: A Systematic Review and Meta-analysis.
    Kota Tokunaga, Yu Fujiwara, Reo Omori, Takumi Sato, Manmeet Singh Ahluwalia, Sarbajit Mukherjee.
       BACKGROUND: Immune checkpoint inhibitors (ICIs) are now standard for various cancers, and preclinical studies suggest beta-blockers (BBs) may boost the efficacy of ICIs. However, prior clinical studies had small sample sizes, requiring large-scale validation.
    OBJECTIVE: We aimed to evaluate the efficacy and safety of combining BBs with ICIs in patients with solid tumors through a systematic review and meta-analysis.
    METHODS: A systematic search of PubMed/MEDLINE and Embase was conducted for studies on BBs plus ICIs for solid tumors up to July 2024. Outcomes of interest were overall survival, progression-free survival, and adverse events. Hazard ratios with 95% confidence intervals were pooled using a random-effects model meta-analysis, with heterogeneity assessed by I2 statistics.
    RESULTS: Overall, 12 clinical studies involving 4293 patients with solid tumors were included, with 1463 patients receiving both BBs and ICIs and 2830 patients receiving ICIs alone. The combination of BBs and ICIs was not associated with a longer overall survival (hazard ratio 1.02; 95% confidence interval 0.84-1.23; p = 0.87; I2 = 69%) or progression-free survival (hazard ratio 0.98; 95% confidence interval 0.80-1.20; p = 0.81; I2 = 71%). Subgroup analyses by cancer types and BB types showed no significant heterogeneity in the hazard ratios for overall survival across different cancer types (I2 = 0%, p for heterogeneity = 0.44) and BB types (I2 = 0%, p for heterogeneity = 0.67). The combination of BBs plus ICIs did not seem to increase toxicity.
    CONCLUSIONS: Despite positive preclinical findings, this meta-analysis showed that adding BBs to ICIs was not associated with longer survival. We await the results of ongoing prospective trials assessing this strategy. PROSPERO REGISTRATION: CRD42024574043.
    DOI:  https://doi.org/10.1007/s11523-025-01184-y
  3. Expert Opin Investig Drugs. 2025 Nov 05.
    Sodium channel modulation as a therapeutic strategy for chemotherapy-induced peripheral neurotoxicity.
    Sara Di Girolamo, Giulia Terribile, Paola Alberti, Guido Cavaletti.
       INTRODUCTION: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common and significant side effect of cancer treatment, triggered by exposure to widely used chemotherapeutic agents such as vinca alkaloids, taxanes, platinum-based compounds, proteasome inhibitors, thalidomide, epothilones, and antibody-drug conjugates. CIPN can be long-lasting or even permanent, leading to a decline in patients' quality of life and negatively impacting the well-being of cancer survivors. It is typically characterized by polyneuropathy or neuronopathy, neuropathic pain, and axonal damage, primarily affecting the peripheral sensory nervous system.
    AREAS COVERED: Emerging evidence suggests that anticancer agents may directly alter neuronal voltage-gated sodium channels (NaV), which could play a crucial role in the development of CIPN. This review explores the mechanisms underlying CIPN, with particular focus on the potential involvement of NaV alterations. Additionally, it examines pharmacological modulators of NaV, offering key insights into the prevention of axonal damage and the management of neuropathic pain associated with CIPN.
    EXPERT OPINION: Despite the availability of various strategies to manage CIPN, there are currently few evidence-based options for its prevention or effective treatment once it develops. As a result, CIPN remains an unmet clinical challenge, highlighting the need for further research into its underlying pathophysiological mechanisms to develop innovative therapies.
    Keywords:  Axonal damage; NaV alterations; NaV1.7-NaV1.8 modulators; chemotherapy-induced peripheral neurotoxicity; dorsal root ganglia; neuronal hyperexcitability; neuropathic pain; voltage-gated sodium channels
    DOI:  https://doi.org/10.1080/13543784.2025.2586615
  4. Eur J Surg Oncol. 2025 Oct 27. pii: S0748-7983(25)00974-6. [Epub ahead of print]52(1): 110546
    Preoperative MRI prediction and molecular pathway study of perineural invasion in intrahepatic cholangiocarcinoma: Insights from bioinformatics approach.
    Mei-Cheng Chen, Xiao-Qi Zhou, Zi-Wei Liu, Mi-Mi Tang, Yu-Ying Chen, Yan-Ji Luo, Ling Ma, Bing Liao, Shi-Ting Feng.
       INTRODUCTION: Perineural invasion (PNI) is a significant factor associated with tumor recurrence and metastasis in intrahepatic cholangiocarcinoma (ICC). This study aims to develop predictive model for PNI in ICC using preoperative MRI features and explore its molecular basis.
    MATERIALS AND METHODS: We analyzed 165 ICC patients from two centers, dividing them into training (n = 120), internal validation (n = 24), and external validation (n = 21) cohorts. Clinical and MRI features associated with PNI were used to construct predictive models. The molecular mechanisms underlying PNI were analyzed using data from The Cancer Genome Atlas (TCGA) and were further validated with a subset of the training cohort.
    RESULTS: The study identified high CEA level, tumor morphology, location, intrahepatic bile duct dilatation, and tumor invasion into the portal vein as independent predictors of PNI. The clinical-radiological model showed an AUC of 0.839 in the training set, with AUCs of 0.754 and 0.872 in the internal and external validation cohorts, respectively. The COL1A1 gene was found to exhibit up-regulation in the PNI-positive group and was closely linked to poorer overall survival (OS). The arterial-phase enhancement pattern, tumor location, and tumor invasion into portal vein were significantly correlated with COL1A1 expression.
    CONCLUSIONS: This preoperative clinical-radiological model effectively predicts PNI in ICC, thereby aiding in the clinical management and prognosis stratification for patients. COL1A1 may serve as a significant biomarker for the development of PNI in ICC, which was significantly correlated with MRI features.
    Keywords:  Bioinformatics; Intrahepatic cholangiocarcinoma; Magnetic resonance imaging; Molecular pathway; Perineural invasion
    DOI:  https://doi.org/10.1016/j.ejso.2025.110546
  5. Front Oncol. 2025 ;15 1559861
    Case Report: Malignant peripheral nerve sheath tumor of the kidney with a novel granular cell morphology.
    Danli Ye, Guangning Yan, Wenzhi Cui, Xuwen Lai, Wenyuan He, Chengyong Lei, Wei Wang.
      Malignant peripheral nerve sheath tumors (MPNSTs) arising from the kidney are rare. The present report describes a renal MPNST of a 33-year-old man exhibiting novel morphological features. Histologically, the tumor was comprised of spindle Schwann cells and granular-like tumor cells. The latter are characterized by large, round-to-polygonal cells with abundant, finely granular eosinophilic cytoplasm, which form variable nodules or are diffusely distributed among the spindle tumor elements. Immunohistochemistry revealed both tumor components expressed CD56, Leu-7, PGP9.5, and Nestin, indicating a neural crest origin. A complete loss of H3K27me3 expression confirmed the diagnosis of MPNST. The patient had no history of neurofibromatosis type 1. The granular cell changes in renal MPNST expand the known morphological spectrum of MPNSTs.
    Keywords:  H3K27me3; case report; granular cell; kidney; malignant peripheral nerve sheath tumor
    DOI:  https://doi.org/10.3389/fonc.2025.1559861
  6. Cancer Diagn Progn. 2025 Nov-Dec;5(6):5(6): 766-771
    Multinodular/Plexiform Schwannoma of the Ankle: A Case Report and Literature Review.
    Yuki Shinohara, Yoshiro Chijiiwa, Jun Nishio.
       Background: Multinodular/plexiform schwannoma is an exceedingly rare benign peripheral nerve sheath tumor that often arises in the dermis or subcutaneous tissue, particularly of the trunk and head and neck region. The ankle is an uncommon location for this peculiar condition.
    Case Report: A 50-year-old man without neurofibromatosis presented with a 10-year history of a slowly growing, occasionally painful mass in the medial aspect of the right ankle. Physical examination revealed a 5-cm, elastic-soft, poorly mobile, non-tender mass. Magnetic resonance imaging (MRI) showed multiple nodular lesions with intermediate signal intensity on T1-weighted sequences and heterogeneous high signal intensity on T2-weighted sequences. Contrast-enhanced MRI demonstrated strong and homogeneous enhancement. After core needle biopsy, the lesions were successfully treated by complete surgical enucleation. Histological examination confirmed the diagnosis of schwannoma consisting of predominantly Antoni A areas. The patient had no evidence of local recurrence and no aggravated neurological deficit at the latest follow-up.
    Conclusion: This unique case provides valuable insights into the understanding and management of multinodular/plexiform schwannoma in the ankle.
    Keywords:  MRI; Multinodular/plexiform schwannoma; ankle; tibial nerve
    DOI:  https://doi.org/10.21873/cdp.10492
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