bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2024–10–20
nine papers selected by
Maksym V. Kopanitsa, Charles River Laboratories



  1. Cancer Cell. 2024 Oct 15. pii: S1535-6108(24)00362-3. [Epub ahead of print]
      Cancer neuroscience is a rapidly growing multidisciplinary field that conceptualizes tumors as tissues fully integrated into the nervous system. Recognizing the complexity and challenges in this field is of fundamental importance to achieving the goal of translational impact for cancer patients. Our commentary highlights key scientific priorities, optimal training settings, and roadblocks to translating scientific findings to the clinic in this emerging field, aiming to formulate a transformative and cohesive path forward.
    DOI:  https://doi.org/10.1016/j.ccell.2024.09.014
  2. Neurobiol Pain. 2024 Jul-Dec;16:16 100167
      Cancer pain is a growing problem, especially with the substantial increase in cancer survival. Reports indicate that bone metastasis, whose primary symptom is bone pain, occurs in 65-75% of patients with advanced breast or prostate cancer. We optimized a preclinical in vivo model of cancer-induced bone pain (CIBP) involving the injection of Lewis Lung Carcinoma cells into the intramedullary space of the femur of C57BL/6 mice or transgenic mice on a C57BL/6 background. Mice gradually reduce the use of the affected limb, leading to altered weight bearing. Symptoms of secondary cutaneous heat sensitivity also manifest themselves. Following optimization, three potential analgesic treatments were assessed; 1) single ion channel targets (targeting the voltage-gated sodium channels NaV1.7, NaV1.8, or acid-sensing ion channels), 2) silencing µ-opioid receptor-expressing neurons by modified botulinum compounds, and 3) targeting two inflammatory mediators simultaneously (nerve growth factor (NGF) and tumor necrosis factor (TNF)). Unlike global NaV1.8 knockout mice which do not show any reduction in CIBP-related behavior, embryonic conditional NaV1.7 knockout mice in sensory neurons exhibit a mild reduction in CIBP-linked behavior. Modified botulinum compounds also failed to cause a detectable analgesic effect. In contrast, inhibition of NGF and/or TNF resulted in a significant reduction in CIBP-driven weight-bearing alterations and prevented the development of secondary cutaneous heat hyperalgesia. Our results support the inhibition of these inflammatory mediators, and more strongly their dual inhibition to treat CIBP, given the superiority of combination therapies in extending the time needed to reach limb use score zero in our CIBP model.
    Keywords:  Acid-sensing ion channels; Cancer-induced bone pain; Dorsal root ganglia; Modified botulinum compounds; Nerve growth factor; Tumor necrosis factor alpha; Voltage-gated sodium channels
    DOI:  https://doi.org/10.1016/j.ynpai.2024.100167
  3. Trends Mol Med. 2024 Oct 17. pii: S1471-4914(24)00265-X. [Epub ahead of print]
      The increasing prevalence and poor prognosis of central nervous system (CNS) metastases pose a significant challenge in oncology, necessitating improved therapeutic strategies. Recent research has shed light on the complex genomic landscape of brain metastases, identifying unique and potentially actionable genetic alterations. These insights offer new avenues for targeted therapy, highlighting the potential of precision medicine approaches in treating CNS metastases. However, translating these discoveries into clinical practice requires overcoming challenges such as availability of tissue for characterization, access to molecular testing, drug delivery across the blood-brain barrier (BBB) and addressing intra- and intertumoral genetic heterogeneity. This review explores novel insights into the evolution of CNS metastases, the molecular mechanisms underlying their development, and implications for therapeutic interventions.
    Keywords:  actionable mutations; blood–brain barrier; brain metastasis; branched evolution; molecular profiling; targeted therapy
    DOI:  https://doi.org/10.1016/j.molmed.2024.09.008
  4. J Natl Compr Canc Netw. 2024 Oct;22(8): 537-542
       BACKGROUND: Cancer-related bone pain remains a prevalent and frequently incapacitating ailment. Although conventional approaches effectively alleviate pain in most individuals, a subset of patients may continue to experience intractable pain. Current recommendations for treating cancer-related bone pain include oral analgesics and multimodal adjuvants, radiation therapy, and, in selected cases, intrathecal therapy. Cancer-related bone pain is mediated by a proliferation of sensory and sympathetic fibers. Thus, we believe that this pain can be successfully managed with minimally invasive sympathetic blockade (SB).
    METHODS: In a retrospective observational cohort, we reviewed patients who underwent single-shot SB for uncontrolled cancer-related bone pain despite receiving opiate analgesics and other interventions. We documented the Edmonton Symptom Assessment Scale (ESAS) ratings, the numeric rating scale (NRS) pain scores, and the morphine equivalent daily dose (MEDD) before and after SB.
    RESULTS: The final cohort included 43 patients (median age, 58 years [range, 23-86 years]) with a history of bone pain experienced for a median of 6 months (IQR, 3-12 months). Comparing before and after the SB, patients had pain reduction -6 (IQR, -7 to -4; P<.001), reduction of ESAS scores of -17 (IQR, -23 to -3; P<.001), and reduction of MEDD -57 mg (95% CI, -79 to -34; P<.001). The treatment was well tolerated.
    CONCLUSIONS: Blockade of sympathetic afferent innervation is an effective and cost-effective modality that can be safely used to palliate intractable pain in patients with malignant bone pain.
    DOI:  https://doi.org/10.6004/jnccn.2024.7028
  5. Neurocirugia (Astur : Engl Ed). 2024 Oct 14. pii: S2529-8496(24)00058-3. [Epub ahead of print]
      Malignant peripheral nerve sheath tumors (MPNST) are uncommon aggressive neoplasms, frequently associated with type I neurofibromatosis. This is the first case of intradural lumbar spine MPNST with intraoperative findings of associated subarachnoid hemorrhage (SAH). A 72-year-old man presented to the emergency department with severe acute low back pain. Neurological examination was unremarkable. Gadolinium-enhanced MRI of the lumbar spine showed an irregularly shaped intradural lesion extending from L3 to L5. The lesion exhibited a medium signal both on T1 and T2-weighted imaging with peripheral enhancement. Through an L3-L5 laminectomy, a diffuse SAH, and a tumor tightly adherent to cauda equina nerve roots were found. Specimen examination revealed a fusocelular tumor with pleomorphic and hyperchromatic nuclei, positive for S100, and SOX10. On an 8-month follow-up, he had no neurological deficit, with a Karnofsky performance score of 90 points. Surgical evidence of SAH in lumbar spine intradural MPNST is a novel finding.
    Keywords:  Cauda Equina; Malignant Peripheral Nerve Sheath Tumor; Subarachnoid Hemorrhage
    DOI:  https://doi.org/10.1016/j.neucie.2024.10.001
  6. Int J Surg Case Rep. 2024 Oct 16. pii: S2210-2612(24)01252-5. [Epub ahead of print]124 110471
       INTRODUCTION: Schwannomas are encapsulated nerve sheath tumors derived from Schwann cells, primarily found in the head, neck, and extremities. Retroperitoneal schwannomas are rare and typically asymptomatic.
    CASE PRESENTATION: A 36-year-old female presented with a long-standing, asymptomatic right lower abdominal mass. Imaging revealed a retroperitoneal cystic mass displacing adjacent structures. The tumor was surgically excised, and histopathology confirmed the diagnosis of schwannoma. The patient had an uneventful postoperative recovery and remains symptom-free with no signs of recurrence.
    DISCUSSION: Schwannomas are benign nerve tumors primarily affecting women aged 30 to 50. This case involved an asymptomatic retroperitoneal schwannoma displacing the inferior vena cava without neurological symptoms. Imaging methods like ultrasound and CT are useful but often lack definitive results, and preoperative biopsy is not recommended due to risks of vascular injury. While conservative management may be suitable for asymptomatic cases, complete surgical excision is crucial to prevent recurrence. Although some suggest partial excision, most literature supports curative resection with negative margins, as incomplete removal can lead to a 10-20 % recurrence rate. The patient underwent successful complete resection.
    CONCLUSION: Retroperitoneal schwannomas are rare tumors that are difficult to diagnose preoperatively. Radiologic findings are usually nondiagnostic. The treatment of choice is complete surgical excision.
    Keywords:  Abdominal mass; Case report; Complete surgical excision; Retroperitoneal schwannoma
    DOI:  https://doi.org/10.1016/j.ijscr.2024.110471
  7. Cancers (Basel). 2024 Sep 26. pii: 3266. [Epub ahead of print]16(19):
      Malignant peripheral nerve sheath tumours (MPNST) are aggressive sarcomas that have nerve sheath differentiation and can present at any anatomical site. They can arise from precursor neurofibroma in the context of neurofibromatosis type 1 (NF1) or as de novo and sporadic tumours in the absence of an underlying genetic predisposition. The primary therapeutic approach is most often radical surgery, with non-surgical modalities playing an important role, especially in locally advanced or metastatic cases. The aim of multimodality approaches is to optimize both local and systemic control while keeping to a minimum acute and late treatment morbidity. Advances in the understanding of the underlying biology of MPNSTs in both sporadic and NF-1-related contexts are essential for the management and implementation of novel therapeutic approaches.
    Keywords:  malignant peripheral nerve sheath tumour; molecular alterations; multimodality management; nerve; neurofibroma; neurofibromatosis type 1
    DOI:  https://doi.org/10.3390/cancers16193266
  8. Asian J Surg. 2024 Oct 16. pii: S1015-9584(24)02293-0. [Epub ahead of print]
      
    Keywords:  Mesentery; Radiology; Schwannomas
    DOI:  https://doi.org/10.1016/j.asjsur.2024.09.220
  9. Radiol Case Rep. 2024 Dec;19(12): 6625-6628
      Ganglioneuromas are rare benign neurogenic tumors of the sympathetic nervous system. Its presence in the neck is relatively rare, characterized by a slow growing mass, usually asymptomatic. Its imaging findings are nonspecific and its diagnosis usually requires surgical biopsy. The treatment of choice is surgical removal. Here, we report the case of a cervical GN in a 16-years-old boy with slowly growing right cervical mass.
    Keywords:  Case report; Cervical masses; Ganglioneuroma; Imaging
    DOI:  https://doi.org/10.1016/j.radcr.2024.09.068