bims-netuvo 2025-04-20 papers

Int J Mol Sci. 2025 Mar 27. pii: 3057. [Epub ahead of print]26(7):

The Use of Neurons Derived from Pluripotent Stem Cells to Study Nerve-Cancer Cell Interactions.

Adriana Jiménez, Adolfo López-Ornelas, Neptali Gutiérrez-de la Cruz, Jonathan Puente-Rivera, Rodolfo David Mayen-Quinto, Anahí Sánchez-Monciváis, Iván Ignacio-Mejía, Exsal M Albores-Méndez, Marco Antonio Vargas-Hernández, Enrique Estudillo.

Tumor innervation is a complex interaction between nerves and cancer cells that consists of axons invading tumors, and its complexity remains largely unknown in humans. Although some retrospective studies have provided important insights into the relationship between nerves and tumors, further knowledge is required about this biological process. Animal experiments have elucidated several molecular and cellular mechanisms of tumor innervation; however, no experimental models currently exist to study interactions between human cancer and nerve cells. Human pluripotent stem cells can differentiate into neurons for research purposes; however, the use of these neurons to study interactions with cancer cells remains largely unexplored. Hence, here we analyze the potential of human pluripotent stem cells to study the interaction of cancer cells and neurons derived from human pluripotent stem cells to unravel the poorly understood mechanisms of human tumor innervation.

Keywords: axonal growth; axonogenesis; neurogenesis; sympathetic neurons; tumor microenvironment; tumor on a chip

DOI: https://doi.org/10.3390/ijms26073057

CNS Neurosci Ther. 2025 Apr;31(4): e70389

Synergistic Inhibition of Nav1.7 and NCX1: A Novel Strategy for Treating Cancer-Induced Bone Pain by Modulating Pain Sensitization and Neuronal Inflammation.

Yan Feng, Fang Yan, Dongtai Chen, Peizong Wang, Yan Yan, Xiangnan Chen, Qiang Li, Wei Xing, Weian Zeng, Yang Huang.

AIMS: Cancer-induced bone pain (CIBP) is a chronic and refractory pain condition characterized by neuronal hyperexcitability, calcium dysregulation, and neuroinflammation. Voltage-gated sodium channels (VGSCs) and sodium/calcium exchangers (NCXs) are crucial in regulating sensory neuron sodium-calcium homeostasis, influencing nociceptive signaling and neuroinflammatory responses. This study focused on exploring how Nav1.7 from the VGSC family and NCX1 from the NCX family influence nociceptive signaling and neuroinflammation in CIBP.
METHODS: CIBP was induced in mice. Nav1.7 and NCX1 expression and colocalization in DRG neurons were analyzed by qPCR, western blotting, and immunofluorescence. Calcium overload and neuronal excitability were assessed using calcium imaging and electrophysiological recordings. Neuroinflammation markers were detected by qPCR and western blotting.
RESULTS: Among the VGSC and NCX subtypes, Nav1.7 and NCX1 were notably upregulated and colocalized in the DRG neurons of CIBP mice. Combined inhibition of these channels demonstrated a synergistic analgesic effect and markedly reduced neuronal calcium overload and hyperexcitability. Furthermore, the combined inhibition substantially alleviated neuroinflammation by inhibiting the p38 MAPK/NF-κB pathway and lowering proinflammatory cytokine levels.
CONCLUSIONS: The combined inhibition of Nav1.7 and NCX1 enhances analgesic effects and reduces neuroinflammation, presenting a potential therapeutic approach for CIBP and other cancer-associated pain disorders.

Keywords: cancer‐induced bone pain; neuroinflammatory response; pain sensitization; sodium‐calcium exchanger 1 (NCX1); synergistic analgesia; voltage‐gated sodium channel 1.7 (Nav1.7)

DOI: https://doi.org/10.1111/cns.70389

Diagnostics (Basel). 2025 Mar 27. pii: 855. [Epub ahead of print]15(7):

Hybrid Benign Peripheral Nerve Sheath Tumors: A Comprehensive Literature Review with Emphasis on Their Clinical, Morphological and Genetic Features.

Serena Salzano, Rosario Caltabiano, Magda Zanelli, Andrea Palicelli, Maurizio Zizzo, Nektarios Koufopoulos, Ioannis Boutas, Gaetano Magro, Valeria Barresi, Giuseppe Broggi.

Hybrid Peripheral Nerve Sheath Tumors (HPNSTs) are rare benign neoplasms that exhibit a combination of histological features from multiple types of benign peripheral nerve sheath tumors, including schwannomas, neurofibromas, and perineuriomas. These tumors present a diagnostic challenge due to their morphological and histological variability. In this article, we aim to summarize the key morphological, histological, and molecular characteristics of HPNSTs, providing insights into their diagnostic approaches. We review the different hybrid subtypes, including schwannoma-perineurioma, schwannoma-neurofibroma, and perineurioma-neurofibroma, emphasizing their clinical features, genetic associations, and the role of surgical excision as the gold-standard treatment.

Keywords: CNS; hybrid benign peripheral nerve sheath tumors; neurofibroma; perineurioma; schwannoma

DOI: https://doi.org/10.3390/diagnostics15070855

Biochem Biophys Rep. 2025 Jun;42 101990

Ion channel mutations and cancer.

Xinyu Cao, Liang Yan, Liang Hong.

Cancer is characterized by uncontrolled growth and spread of abnormal cells, driven by genetic, environmental, and lifestyle factors. Genetic mutations contribute to hallmark processes of cancer progression such as sustained proliferation, apoptosis resistance, and immune evasion. Ion channels are pore-forming transmembrane proteins that regulate ion transport across cellular membranes, influencing various cellular functions. Recent studies have indicated the emerging roles of ion channel proteins in cancer. Ion channels are critical for cellular processes like proliferation, apoptosis, migration, and angiogenesis, and dysregulation of ion channels by genetic mutations disrupts these processes, enabling tumor growth, invasion, and metastasis. Ion channel gene mutations have been associated with various cancer subtypes. These ion channel mutations either dysregulate ion channel activity associated with intracellular signaling pathways in cell survival and division, or influence the tumor microenvironment by modifying pH, oxygenation, or ion concentrations, which might facilitate tumor growth and gene expression and contribute to oncogenesis. In the present review, we discuss ion channel regulation of cancer biology and summarize recent studies in ion channel mutations associated with cancer.

Keywords: Cancer; Gene; Ion channel; Mutation; Variant

DOI: https://doi.org/10.1016/j.bbrep.2025.101990

Adv Ther. 2025 Apr 15.

Lidocaine-A Promising Candidate for the Treatment of Cancer-Induced Bone Pain: A Narrative Review.

Lihan Luo, Yuqi Cheng, Hanxi Wang, Li Li, Hanyun Niu, Yuzhu Yang, Qianqian Zhou, Jiannan He, Jianhong Xu.

Pain is one of the most common symptoms in patients with cancer, with cancer-induced bone pain (CIBP) significantly affecting their quality of life. Opioids are commonly used as first-line treatments for cancer pain, but their use requires caution due to non-mechanistic analgesia and significant side effects. As a result, there is a need for new non-opioid drugs that target cancer pain through specific mechanisms. Recent studies on the anticancer effects of lidocaine have highlighted its potential benefits in both treating cancer and alleviating cancer-induced pain. This article discusses the mechanism of action and clinical applications of lidocaine in cancer pain management, and suggests new treatment approaches for patients with CIBP.

Keywords: Cancer-induced bone pain; Lidocaine; Pain management

DOI: https://doi.org/10.1007/s12325-025-03192-w