bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2025–05–04
twelve papers selected by
Maksym V. Kopanitsa, Charles River Laboratories



  1. BMJ Support Palliat Care. 2025 May 02. pii: spcare-2025-005483. [Epub ahead of print]
      Patients with cancer are often polysymptomatic due to significant disease and treatment-related morbidity. Vagus nerve stimulation (VNS), a type of neuromodulation, affects various physiological processes that are highly relevant to many cancer-related symptoms. It is an emerging therapy that uses the omnipotent nature of the nerve and is known to ameliorate conditions such as depression, epilepsy, gastrointestinal disorders and migraine. Given the evidence base for VNS and its proven utilisation outside of cancer, we suggest research and clinical application of this treatment modality in supportive oncology.
    Keywords:  Cancer; Chronic conditions; Palliative Care; Prognosis; Supportive care; Symptoms and symptom management
    DOI:  https://doi.org/10.1136/spcare-2025-005483
  2. J Immunother Cancer. 2025 May 02. pii: e011609. [Epub ahead of print]13(5):
      A tumor's ability to attract innervation is a critical factor in tumor progression and immune escape, with the sympathetic nervous system playing a major role. Catecholamines released by sympathetic nerves activate adrenergic receptors on tumor cells, enhancing growth and resistance to therapies, while activation of adrenergic receptors on immune cells triggers immunosuppressive activity in the tumor microenvironment. Nerve growth factor (NGF) produced by tumor cells is a key driver of tumor innervation, making it a promising target for novel therapeutic strategies. In this commentary, we highlight a recent study by Yang et al, which examines NGF single-chain variable fragment (scFv)-secreting chimeric antigen receptor(CAR) T cells and the impact of NGF neutralization by CAR T cells on CAR T-cell function and the remodeling of the tumor microenvironment. This work shows that we may be able to exploit a tumor-derived survival factor as a vulnerability and a means to enhance antitumor immune activity.
    Keywords:  Chimeric antigen receptor - CAR; Immunosuppression; Tumor microenvironment - TME
    DOI:  https://doi.org/10.1136/jitc-2025-011609
  3. World J Surg Oncol. 2025 Apr 26. 23(1): 164
       BACKGROUND: To develop and validate an MRI-based fusion model for preoperative prediction of perineural invasion (PNI) status in patients with intrahepatic cholangiocarcinoma (ICC).
    METHODS: A retrospective collection of 192 ICC patients from three medical centers (training set: n = 147; external test set: n = 45) was performed. Patients were classified into the PNI-positive and PNI-negative groups based on postoperative pathological results. After image preprocessing, a total of 1,197 features were extracted from T2-weighted imaging (T2WI). Feature selection was performed, and a radiomics model was constructed using machine learning algorithms, followed by SHapley Additive exPlanations (SHAP) visualization. Subsequently, a deep learning model was constructed based on the pre-trained ResNet101, with Gradient-weighted Class Activation Mapping (Grad-CAM) used for visualization. Finally, a fusion model incorporating deep learning, radiomics, and clinical features was developed using logistic regression, and visualization was performed with a nomogram. The predictive performance of the model was evaluated based on the area under the curve (AUC), calibration curves, and decision curve analysis (DCA).
    RESULTS: The fusion model, which integrates deep learning signature, radiomics signature, and two clinical features, demonstrated strong discrimination for PNI status. In the training set, the AUC was 0.905, with an accuracy of 0.823; in the external test set, the AUC was 0.760, with an accuracy of 0.778. Visualization methods provided support for the practical application of the model.
    CONCLUSION: The fusion model aids in the preoperative identification of PNI status in patients with ICC, and may help guide clinical decision-making regarding preoperative staging and adjuvant therapy.
    Keywords:  Deep learning; Intrahepatic cholangiocarcinoma; Magnetic resonance imaging; Perineural invasion; Radiomics
    DOI:  https://doi.org/10.1186/s12957-025-03819-w
  4. Front Oncol. 2025 ;15 1541413
       Purpose: This study aims to detect vascular and neural invasion in prostate cancer through MRI, utilize habitat analysis of the tumor microenvironment, construct a radiomic feature model, thereby enhancing diagnostic accuracy and prognostic assessment for prostate cancer, ultimately improving patients' quality of life.
    Methods: We retrospectively collected records of 400 patients with pathologically verified prostate cancer from January to December 2023. We developed a radiomic features model within the tumor habitat using MRI data and identified independent risk factors through multivariate analysis to construct a clinical model. Finally, we assessed the performance of these features using the DeLong test (through the area under the receiver operating characteristic curve, AUC), evaluated the calibration curve with the Hosmer-Lemeshow test, and performed decision curve analysis.
    Results: In the training set, the optimal algorithm based on the intratumoral heterogeneity score had an AUC value of 0.882 (CI: 0.843-0.921); in the test set, the AUC value was 0.860 (CI: 0.792-0.928). The traditional radiomics model (considering the entire tumor) had an AUC value of 0.761 (CI: 0.695-0.827) in the training set and 0.732 (CI: 0.630-0.834) in the test set. The combined model that integrates habitat scores and Gleason scores had an AUC value of 0.889 (CI: 0.8509-0.9276) in the training set and 0.886 (CI: 0.8183-0.9533) in the test set, outperforming the single models.
    Conclusions: By deeply analyzing the tumor microenvironment and combining radiomics models, the diagnostic precision and predictive accuracy of vascular and nerve invasion in prostate cancer can be significantly improved. This approach provides a valuable tool for optimizing treatment plans, improving patient prognosis, and reducing unnecessary medical interventions.
    Keywords:  MRI; habitat imaging; prostate cancer; radiomediography; tumor microenvironments
    DOI:  https://doi.org/10.3389/fonc.2025.1541413
  5. Case Rep Oncol. 2025 Jan-Dec;18(1):18(1): 531-538
       Introduction: Malignant peripheral nerve sheath tumors (MPNSTs) are common in the peripheral nerves of the head, neck, and limbs, with few reports of their occurrence in the breasts, and the epithelioid type is rare. Here, we aimed to report a case of an epithelioid MPNST of the breast.
    Case Presentation: A 76-year-old woman presented with bilateral breast masses. Pathological findings showed a 60-mm invasive ductal carcinoma (T3N0M0 stage IIB) on the right breast and an epithelioid MPNST on the left breast. After surgical resection, the patient was treated with endocrine therapy alone for right breast cancer, and no recurrence was observed 4 years after surgery.
    Conclusion: Reports of MPNSTs in the breasts are rare. The pathological analysis showed atypia of spindle cells, positive staining for vimentin, S100, SOX10, and epithelial-like cells, and positive staining for cytokeratin AE1/AE3. H3K27me3 is reportedly absent in typical MPNSTs; however, it is expressed in epithelioid types. It sometimes occurs in patients with a germline mutation in SMARCB1/INI1, where INI1 is absent in tumor cells. In this case, the tumor cells expressed H3K27me3 and also maintained INI1.
    Keywords:  Breast; Epithelioid type; Malignant peripheral nerve sheath tumor
    DOI:  https://doi.org/10.1159/000545496
  6. Cancers (Basel). 2025 Apr 18. pii: 1357. [Epub ahead of print]17(8):
       BACKGROUND/OBJECTIVES: Beta adrenergic signaling has been implicated in cancer progression, leading to interest in repurposing beta blockers (BBs) as adjunctive anti-cancer agents. However, clinical findings are inconsistent. This systematic review and meta-analysis evaluates the association between BB use and survival outcomes in cancer patients.
    METHODS: A systematic search of OVID Medline, EMBASE, and CENTRAL was conducted through 13 September 2023, for studies comparing survival outcomes in solid tumor patients using BBs versus non-users. Eligible studies reported hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS), or cancer-specific survival (CSS). Perioperative studies and those without BB-specific HRs were excluded. Data extraction and quality assessment were performed in duplicate using ROBINS-I. A random-effects model was used, with heterogeneity assessed by the I2 statistic.
    RESULTS: Seventy-nine studies (492,381 patients) met the inclusion criteria; 2.5% were prospective. The most frequently studied cancers were breast (n = 33), ovarian (n = 30), and colorectal (n = 28). BB use was associated with improved PFS (HR 0.78, 95% CI: 0.66-0.92, I2 = 79.8%), with significance maintained after excluding high-bias studies (HR 0.74, 95% CI: 0.61-0.91, I2 = 36.6%). No significant associations were observed for OS (HR 0.99, 95% CI: 0.94-1.04, I2 = 84.9%) or CSS (HR 0.95, 95% CI: 0.91-1.00, I2 = 77.4%).
    CONCLUSIONS: BB use may be associated with longer PFS in cancer patients, but findings are limited by study design and heterogeneity; high-quality prospective studies are needed.
    Keywords:  beta blockers; cardio-oncology; drug repurposing; pharmacology
    DOI:  https://doi.org/10.3390/cancers17081357
  7. Oper Neurosurg (Hagerstown). 2025 Apr 28.
       BACKGROUND AND OBJECTIVES: Pain is the cardinal symptom of non-neurofibromatosis type 2 schwannomatosis (non-NF2-SWN), and peripheral nerve schwannomas are the most frequent tumors encountered in this condition. The role of surgery in alleviating schwannoma-associated pain in schwannomatosis remains a matter of debate in the literature.
    METHODS: We conducted a retrospective chart review of all non-NF2-SWN patients followed up at our Schwannomatosis Reference Center and included all patients operated from a peripheral nerve tumor. NF2-related schwannomatosis was excluded on the basis of germline genetic study and/or absence of suggestive tumors on brain and spine MRIs.
    RESULTS: Fifty-nine patients were included, suffering mostly from a nonfamilial (50/59, 85%) and diffuse (40/59, 68%) non-NF2-SWN. A germline genetic study of the NF2, LZTR1, and SMARCB1 genes was performed in 38 patients (64%) and demonstrated a LZTR1 gene variant in 19 cases (50%). The patients were operated from 103 peripheral nerve tumors, mainly located in major nerves (n = 67, 65%) compared with subcutaneous (n = 17, 16%) and intramuscular (n = 17, 16%) cases. Most tumors were classical discrete tumors (n = 88, 85%), while multinodular cases represented only 15% (n = 15) of cases. Pathological analysis confirmed the diagnosis of schwannoma except 2 cases of hybrid neurofibroma/schwannoma tumors. A complete resection was performed in 89% of cases with a complete relief of preoperative pain in 87% of cases. Postoperative motor and sensory deficits were encountered in 8 (8%) and 14 (14%) cases, respectively. Multinodular schwannomas were characterized by a decreased rate of complete pain relief (64% vs 90%, P = .007) and an increased rate of postoperative motor deficit (3% vs 35%, P < .001) compared with discrete tumors.
    CONCLUSION: Nerve-sparing surgery using intraoperative neuro-monitoring remains effective in treating pain of non-NF2-SWN-associated peripheral nerve schwannomas, with the notable exception of multinodular tumors, also characterized by an increased rate of postoperative motor deficits.
    Keywords:  ; Neurofibroma; Peripheral nerve sheath tumor; Peripheral neuropathy; Schwannoma; Schwannomatosis
    DOI:  https://doi.org/10.1227/ons.0000000000001595
  8. Neurosurg Focus. 2025 May 01. 58(5): E2
       OBJECTIVE: Schwannomatosis is a rare genetic predisposition to develop multiple nonintradermal schwannomas affecting the spine and peripheral nerves, excluding vestibular schwannomas. Schwannomatosis-associated schwannomas can present with pain or motor deficits, prompting resection. In this study, the authors reported the clinical characteristics, surgical interventions, and postoperative outcomes of patients with schwannomatosis-related schwannomas treated with resection.
    METHODS: This was a retrospective cohort study of adult patients with schwannomatosis who had undergone resection of a symptomatic peripheral or spinal schwannoma at the authors' institution from September 2003 to June 2023. Data were extracted from electronic health records and provider notes.
    RESULTS: A cohort of 85 patients (57.6% women) had a mean follow-up of 68.4 ± 58.2 months after surgery. The mean age at the time of surgery was 44.6 ± 16.5 years. Pain was the most common presenting symptom (94.1%), followed by motor weakness (36.4%) and sensory deficits (32.9%). Just under two-thirds of the patients (64.7%) had undergone prior surgery for schwannoma, 20 (36.4%) of whom had a prior resection in the same exact location. Gross-total resection (GTR) was achieved in 88.2% of cases and en bloc resection in 69.4%. There were significant improvements in pain, motor weakness, and sensory deficits at the last postoperative follow-up visit. There was local tumor recurrence in 14 patients (16.5%), and the overall mortality rate was 4.7%. Univariate and multivariate analyses identified GTR as the strongest predictor of a decreased risk of local recurrence (HR 0.09, 95% CI 0.02-0.48, p = 0.005).
    CONCLUSIONS: Patients with schwannomatosis commonly presented with neurological symptoms of pain, sensory deficits, or motor weakness associated with their schwannomas. Resection significantly improved their preoperative symptoms, and GTR was associated with a decreased risk of local recurrence.
    Keywords:  outcomes; recurrence; schwannomatosis; surgery; survival
    DOI:  https://doi.org/10.3171/2025.2.FOCUS24751
  9. Med Oncol. 2025 Apr 26. 42(6): 181
      Pancreatic cancer is a highly lethal malignancy, and perineural invasion (PNI) is a common pathological feature that significantly contributes to poor prognosis. Our research identified TGFBI as a key player in PNI development. The expression of TGFBI in tissue and cancer cells were detected by RT-qPCR, Western blot, Immunohistochemistry, and ELISA. The localization of TGFBI in cells was analyzed by Immunofluorescence staining (IF). The neural invasion ability of cancer cells were assessed by in vitro neural invasion model. Moreover, Western blot was used to investigate epithelial-mesenchymal transition (EMT) markers and PI3K/AKT pathway markers to elucidate the underlying mechanisms. Finally, an in vivo neural invasion model was used to verify the tumorigenic ability of the cancer cells in the sciatic nerve. Our findings highlight that TGFBI is up-regulated in PNI tissue and significantly correlates with poor prognosis in pancreatic cancer patients. Based on in vitro experiments, knockdown of TGFBI reduced neural invasion, as well as EMT, whereas rTGFBI exhibited the reverse effect. Knockdown of TGFBI reduced PI3K/AKT phosphorylation in Capan-2 and CFPAC-1. Moreover, PI3K inhibitor LY294002 was observed to counteract the effects of TGFBI on neural invasion, and EMT in Capan-2 and CFPAC-1. In vivo, knockdown of TGFBI inhibited tumor formation in the sciatic nerve of mice. Finally, we confirmed TGFBI as potential biomarker for PNI and prognosis of pancreatic cancer. Collectively, we concluded that TGFBI activates the PI3K-AKT pathway in pancreatic cancer cells, ultimately promoting EMT and leading to PNI.
    Keywords:  EMT; Pancreatic cancer; Perineural invasion; TGFBI
    DOI:  https://doi.org/10.1007/s12032-025-02736-y
  10. Cancer Lett. 2025 Apr 25. pii: S0304-3835(25)00305-2. [Epub ahead of print]624 217739
      Metastatic progression drives the majority of cancer-related fatalities, and involvement of the central nervous system (CNS) poses especially formidable challenges to patients and clinicians. Brain metastases (BrM), commonly originate from lung, breast and melanoma cancers, and carry disproportionately poor outcomes. Although therapeutic advances have extended survival for many extracranial tumors, BrM incidence continues to climb-underscoring critical knowledge gaps in understanding the unique biology of tumor colonization in the CNS. While definitive evidence remains limited, a growing focus on cancer neuroscience-especially regarding hormone dependent cancer cells in the brain-has begun to reveal that factors normally regulated by sex steroids and neurosteroids may similarly influence the specialized metastatic microenvironment in the CNS. Steroid hormones can permeate the blood-brain barrier (BBB) or be synthesized de novo by astrocytes and other CNS-resident cells, potentially influencing processes such as inflammation, synaptic plasticity, and immune surveillance. However, how these hormonal pathways are co-opted by disseminated cancer cells remains unclear. Here, we review the complex hormonal landscape of the adult brain and examine how neuroendocrine-immune interactions, often regulated by sex hormones, may support metastatic growth. We discuss the interplay between systemic hormones, local steroidogenesis, and tumor adaptation to identify novel therapeutic opportunities.
    Keywords:  Brain metastasis; Cancer neuronal interaction; Hormones; Neurotransmitters; Sex steroids
    DOI:  https://doi.org/10.1016/j.canlet.2025.217739
  11. Cancer Lett. 2025 Apr 24. pii: S0304-3835(25)00314-3. [Epub ahead of print]624 217748
      Cancer neuroscience, a burgeoning field, investigates the complex interactions between cancer and the nervous system, emphasizing how cancer cells exploit neuronal components for growth and metastasis. Tumor-associated Schwann cells (TASc) have emerged as crucial players in the progression of highly innervated cancers, highlighting the intricate relationship between the tumor microenvironment (TME) and the nervous system. This review concludes how TASc, as the most abundant glial cell in the peripheral nervous system, contribute to tumor growth, metastasis, and the remodeling of the TME. Acting similarly to reactive astrocytes in the central nervous system, TASc are implicated in driving perineural invasion (PNI), a distinctive cancer progression pathway facilitating tumor infiltration and metastasis. These TASc not only contribute indirectly to pain but also promote tumor recurrence and poor prognosis. Intrinsic to their role, TASc exhibit unique gene expression profiles and phenotypic transformations, shifting from myelinating to non-myelinating states, thereby actively participating in metastasis and the remodeling of the tumor microenvironment. Targeting TASc represents a novel and promising therapeutic strategy in non-neurological cancers, offering new avenues for clinical intervention.
    Keywords:  Cancer neuroscience; Neuro-cancer interaction; Neuro-oncology; Schwann cells; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.canlet.2025.217748
  12. Front Cell Dev Biol. 2025 ;13 1587548
      Gynecological cancers remain a leading cause of cancer among female patients, and surgery continues to be the primary therapeutic approach. Anesthesia is an indispensable component of perioperative period. In recent years, the influence of anesthesia drugs on cancer has become one of the focuses of anesthesiologists. Anesthetic drugs may influence cancer metabolic reprogramming and modulate immune function through the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). Emerging evidence suggests that the choice of anesthetic agents could affect the prognosis of gynecological cancers. This review explores the relationship between anesthetic drugs and gynecological cancers (cervical cancer, ovarian cancer, and endometrial cancer), elucidating their effects on cancer prognosis through cellular pathways, metabolic regulation, and immune mechanisms. The findings aim to guide clinical decision-making and evaluate optimal perioperative anesthetic management strategies for gynecological cancer patients.
    Keywords:  cervical cancer; dexamethasone; endometrial cancer; intravenous anesthetics; local anesthetics; opioids; ovarian cancer; volatile anesthetics
    DOI:  https://doi.org/10.3389/fcell.2025.1587548