bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2024–03–03
nine papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute
  1. Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment.
  2. Role of Serotonergic System in Regulating Brain Tumor-Associated Neuroinflammatory Responses.
  3. Cancer-induced morphological changes in enteric glial cells in the jejunum of Walker-256 tumor-bearing rats.
  4. Schwannoma of the Sigmoid Colon: A Rare Case.
  5. Sacral nerve root metastasis in a patient with lung carcinoma resembling neurinoma - a case report and literature review.
  6. Low-Grade Malignant Peripheral Nerve Sheath Tumor: A Case Report of Exceptional Parapatellar Location in the Knee.
  7. Intramuscular Hybrid Nerve Sheath Tumor of the Thigh: Case Report and Literature Review.
  8. Fibrolipomatous Hamartoma Over the Left Forearm and Palm.
  9. Esketamine inhibits the JNK-c-Jun pathway in the spinal dorsal horn to relieve bone cancer pain in rats.
  1. Cancer Cell. 2024 Feb 13. pii: S1535-6108(24)00037-0. [Epub ahead of print]
    Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment.
    Xue-Yan He, Yuan Gao, David Ng, Evdokia Michalopoulou, Shanu George, Jose M Adrover, Lijuan Sun, Jean Albrengues, Juliane Daßler-Plenker, Xiao Han, Ledong Wan, Xiaoli Sky Wu, Longling S Shui, Yu-Han Huang, Bodu Liu, Chang Su, David L Spector, Christopher R Vakoc, Linda Van Aelst, Mikala Egeblad.
      Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients, yet the reasons are unclear. We show that chronic stress increases lung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stress significantly alters the lung microenvironment, with fibronectin accumulation, reduced T cell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolishes stress-induced metastasis. Chronic stress shifts normal circadian rhythm of neutrophils and causes increased neutrophil extracellular trap (NET) formation via glucocorticoid release. In mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress fails to increase NETs and metastasis. Furthermore, digesting NETs with DNase I prevents chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease.
    Keywords:  breast cancer; chronic stress; glucocorticoids; metastasis; metastatic niche; neutrophil extracellular traps; tumor microenvironment; tumor-host interactions
    DOI:  https://doi.org/10.1016/j.ccell.2024.01.013
  2. Methods Mol Biol. 2024 ;2761 181-207
    Role of Serotonergic System in Regulating Brain Tumor-Associated Neuroinflammatory Responses.
    Surojit Karmakar, Girdhari Lal.
      Serotonin signaling regulates wide arrays of both neural and extra-neural functions. Serotonin is also found to affect cancer progression directly as well as indirectly by modulating the immune cells. In the brain, serotonin plays a key role in regulating various functions; disturbance of the normal activities of serotonin leads to various mental illnesses, including the neuroinflammatory response in the central nervous system (CNS). The neuroinflammatory response can be initiated in various psychological illnesses and brain cancer. Serotonergic signaling can impact the functions of both glial as well as the immune cells. It can also affect the tumor immune microenvironment and the inflammatory response associated with brain cancers. Apart from this, many drugs used for treatment of psychological illness are known to modulate serotonergic system and can cross the blood-brain barrier. Understanding the role of serotonergic pathways in regulating neuroinflammatory response and brain cancer will provide a new paradigm in modulating the serotonergic components in treating brain cancer and associated inflammation-induced brain damages.
    Keywords:  Cancer; Cytokines; Glioblastoma; Glioma; Immunity; Neuroinflammation; Serotonin
    DOI:  https://doi.org/10.1007/978-1-0716-3662-6_14
  3. Acta Histochem. 2024 Feb 28. pii: S0065-1281(24)00014-X. [Epub ahead of print]126(3): 152146
    Cancer-induced morphological changes in enteric glial cells in the jejunum of Walker-256 tumor-bearing rats.
    Fabiana Galvão da Motta Lima, Maysa Pacheco Alvarez da Silva, Sabrina Silva Sestak, Flávia Alessandra Guarnier, Ana Paula de Oliveira, João Victor Kuller, Brian David Gulbransen, Juliana Vanessa Colombo Martins Perles, Jacqueline Nelisis Zanoni.
      Cancer-induced cachexia is associated with systemic inflammation and gastrointestinal dysfunction. How changes to cells of the enteric nervous system contribute to gut dysfunction in tumor development and cancer cachexia is unknown. Here, we tested the hypothesis that changes to enteric glia, a type of peripheral glia that surround enteric neurons and regulate gut homeostasis, are associated with tumor development and that supplementing with the antioxidant L-glutathione is protective against the changes induced. Immunohistochemistry for neurons, enteric glial cells and immune cells was performed in whole-mount preparations and frozen histological sections of the jejunum from 20 Wistar rats, distributed in 4 groups: control, tumor of Walker-256, control administered with 1 % L-glutathione, and tumor of Walker-256 administered with 1 % L-glutathione. Morphoquantitative analyses were made using Image-Pro® Plus 4.5 and ImageJ® 1.43° software. Tumor development significantly reduced neuronal and glial cell populations in the myenteric and submucosal plexuses and enlarged glial cell body area in the submucosal plexus. In contrast, tumors increased glia in the jejunal mucosa and this effect was accompanied by B-lymphocyte recruitment. GSH-supplemented diet was not sufficient to protect against changes to neurons and glia in the submucosal plexus but was partially protective in the myenteric plexus. L-glutathione had no effect on physiological parameters of cachexia but was sufficient to preserve enteric glial cell density in the myenteric plexus. These results suggest that changes to both enteric neurons and glia likely contribute to the gastrointestinal effects of tumor development and that oxidative stress contributes to these effects in the enteric nervous system.
    Keywords:  Cachexia; Cancer; Enteric Glial Cells; L-glutathione; Morphology
    DOI:  https://doi.org/10.1016/j.acthis.2024.152146
  4. Cureus. 2024 Jan;16(1): e53140
    Schwannoma of the Sigmoid Colon: A Rare Case.
    Bushra A Zainaldeen, Amr S Alaus, Mariam AlKooheji, Jaffar Alkhuzaie, Safa Alshaikh.
      Schwannoma is a type of peripheral nerve sheath tumor that is often found in the head and neck. Schwannomas in the digestive system, particularly the colon and rectum, are exceptionally rare, and they are mostly non-malignant and asymptomatic although sometimes patients can present with symptoms similar to those observed in patients with other gastrointestinal tumors like abdominal pain, fullness, nausea, vomiting, and change in bowel habits. For diagnosis and treatment, surgical resection along with biopsy is the gold standard. In this paper, we describe a rare case of sigmoid schwannoma that was successfully treated in our department by surgical resection.
    Keywords:  colon; gastrointestinal; peripheral nerve sheath tumor; schwannoma; sigmoid
    DOI:  https://doi.org/10.7759/cureus.53140
  5. Folia Med (Plovdiv). 2024 Feb 29. 66(1): 136-141
    Sacral nerve root metastasis in a patient with lung carcinoma resembling neurinoma - a case report and literature review.
    Ivo Kehayov, Atanas Davarski, Polina Angelova, Borislav Kitov.
      Intradural extramedullary metastases from systemic neoplasms are very rare, with an incidence ranging from 2% to 5% of all secondary spinal diseases. We present the case of a 53-year-old man diagnosed with lung adenocarcinoma with symptoms of severe back pain and tibial paresis. The magnetic resonance imaging (MRI) revealed an intradural lesion originating from the right S1 nerve root mimicking neurinoma. Total tumor removal was achieved via posterior midline approach. The histological examination was consistent with lung carcinoma metastasis. Due to the rarity of single nodular nerve root metastases, MRI images may be misinterpreted as nerve sheath tumors, such as schwannomas or neurofibromas. We performed a brief literature review outlining the mainstay of diagnosis, therapeutic approach, and the prognosis of these rare lesions.
    Keywords:  intradural leptomeningeal metastasis MRI nerve root spine surgery
    DOI:  https://doi.org/10.3897/folmed.66.e111619
  6. Cureus. 2024 Jan;16(1): e52739
    Low-Grade Malignant Peripheral Nerve Sheath Tumor: A Case Report of Exceptional Parapatellar Location in the Knee.
    Mohammed Barrached, Achraf Tebbaa El Hassali.
      Malignant tumors of the peripheral nerve sheaths are uncommon, constituting a small percentage, typically ranging from 2% to 5% of soft tissue sarcomas. Etiological diagnosis is often difficult but is guided by imaging and confirmed by histopathological and immunohistochemical examination. We report a case of a 46-year-old woman admitted for management of a mass in the medial parapatellar region of the right knee. Her medical history included a burn to the right leg five years ago and a previously undocumented resection of a medial parapatellar tissue mass in the right knee. Radiological examination showed a deep and superficial soft tissue mass in the medial soft tissue of the right knee opposite the patella, with no hemorrhagic components and heterogeneous enhancement after injection of gadolinium. Histopathology confirmed the diagnosis of a low-grade peripheral nerve sheath tumor, and a thoracic-abdominal-pelvic CT scan was performed, which was normal. Treatment consisted of a simple carcinological resection and local radiotherapy. No local recurrence was noted after one year of follow-up.
    Keywords:  diagnosis; exceptional location; knee; malignant tumor of the peripheral nerve sheaths; nerve tumors
    DOI:  https://doi.org/10.7759/cureus.52739
  7. In Vivo. 2024 Mar-Apr;38(2):38(2): 971-974
    Intramuscular Hybrid Nerve Sheath Tumor of the Thigh: Case Report and Literature Review.
    Yoshiro Chijiiwa, Junya Sano, Kazuhiko Okamura, Jun Nishio.
       BACKGROUND/AIM: Hybrid nerve sheath tumor (HNST) is a benign peripheral nerve sheath tumor with combined features of more than one histological type, such as schwannoma, neurofibroma, and perineurioma. It remains under-recognized in routine clinical practice. Herein, we describe an unusual case of intramuscular HNST of the thigh.
    CASE REPORT: The patient was a 41-year-old man with no history of trauma who presented with a 3-month history of a palpable mass in the right thigh. Physical examination revealed a 4-cm, elastic hard, mobile, nontender mass. Magnetic resonance imaging exhibited a well-circumscribed intramuscular mass with low-to-intermediate signal intensity on T1-weighted sequences and higher signal intensity peripherally and lower signal intensity centrally, representing a target sign, on T2-weighted sequences. Complete surgical excision of the tumor was carried out. Microscopically, the tumor showed dual histological components of both schwannoma and neurofibroma. Immunohistochemically, the schwannomatous component was strongly and diffusely positive for S-100 protein and negative for CD34, while the neurofibromatous component contained CD34-positive fibroblasts and S-100 protein-positive Schwann cells. Epithelial membrane antigen was negative for both components. These findings were consistent with a diagnosis of HNST (hybrid schwannoma/neurofibroma). The patient had no evidence of local recurrence and no neurological deficit at the final follow-up.
    CONCLUSION: Although extremely rare, HNST should be included in the extended differential diagnosis of a well-circumscribed, intramuscular soft-tissue mass in the extremities, particularly in young and early middle-aged adults.
    Keywords:  Hybrid nerve sheath tumor; intramuscular; magnetic resonance imaging; neurofibroma; schwannoma
    DOI:  https://doi.org/10.21873/invivo.13529
  8. J Orthop Case Rep. 2024 Feb;14(2): 34-38
    Fibrolipomatous Hamartoma Over the Left Forearm and Palm.
    Sanjay Kumar Giri, M Vishnu Swaroop Reddy, Santanu Suba, Suvendu Purkait, Mantu Jain.
       Introduction: Fibrolipomatous hamartomas are rare congenital benign tumors that can affect the nerves. The symptoms arise due to compression and may require surgical excision.
    Case Report: A man in his mid-20s suffered swelling over the volar aspect of the left forearm and hand for 4 months. He was symptomatic. A soft, non-tender swelling of size 6 × 4 cm was present over the flexor aspect of the left forearm and palm, with features suggestive of median nerve compression. Magnetic resonance imaging and electromyography were performed. Decompression of the carpal tunnel was performed with debulking of fibrofatty elements and fine dissection of the neural elements.
    Conclusion: This case report demonstrates a rare fibrolipomatous hamartoma encompassing the median nerve, which required surgical excision.
    Keywords:  Fibrolipomatous hamartoma; median nerve; surgical excision
    DOI:  https://doi.org/10.13107/jocr.2024.v14.i02.4208
  9. Mol Pain. 2024 Feb 28. 17448069241239231
    Esketamine inhibits the JNK-c-Jun pathway in the spinal dorsal horn to relieve bone cancer pain in rats.
    Chenxia Duan, Yi Zhu, Zhuoliang Zhang, Tiantian Wu, Mengwei Shen, Jinfu Xu, Wenxin Gao, Jianhua Pan, Lei Wei, Huibin Su, Chenghuan Shi.
      Cancer-induced bone pain (CIBP) is one of the most common and feared symptoms in patients with advanced tumors. The X-C motif chemokine ligand 12 (CXCL12) and the CXCR4 receptor have been associated with glial cell activation in bone cancer pain. Moreover, mitogen-activated protein kinases (MAPKs), as downstream CXCL12/CXCR4 signals, and c-Jun, as activator protein AP-1 components, contribute to the development of various types of pain. However, the specific CIBP mechanisms remain unknown. Esketamine is a non-selective N-methyl-D-aspartic acid receptor (NMDA) inhibitor commonly used as an analgesic in the clinic, but its analgesic mechanism in bone cancer pain remains unclear. We used a tumor cell implantation (TCI) model and explored that CXCL12/CXCR4, p-MAPKs, and p-c-Jun were stably up-regulated in the spinal cord. Immunofluorescence images showed activated microglia in the spinal cord on day 14 after TCI and co-expression of CXCL12/CXCR4, p-MAPKs (p-JNK, p-ERK, p-p38 MAPK), and p-c-Jun in microglia. Intrathecal injection of the CXCR4 inhibitor AMD3100 reduced JNK and c-Jun phosphorylations, and intrathecal injection of the JNK inhibitor SP600125 and esketamine also alleviated TCI-induced pain and reduced the expression of p-JNK and p-c-Jun in microglia. Overall, our data suggest that the CXCL12/CXCR4-JNK-c-Jun signaling pathway of microglia in the spinal cord mediates neuronal sensitization and pain hypersensitivity in cancer-induced bone pain and that esketamine exerts its analgesic effect by inhibiting the JNK-c-Jun pathway.
    Keywords:  CIBP; CXCL12; CXCR4; Esketamine; JNK; c-Jun
    DOI:  https://doi.org/10.1177/17448069241239231
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