bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2023–12–17
fourteen papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute



  1. Oncogene. 2023 Dec 11.
      Gastrointestinal (GI) cancer is a formidable malignancy with significant morbidity and mortality rates. Recent studies have shed light on the complex interplay between the nervous system and the GI system, influencing various aspects of GI tumorigenesis, such as the malignance of cancer cells, the conformation of tumor microenvironment (TME), and the resistance to chemotherapies. The discussion in this review first focused on exploring the intricate details of the biological function of the nervous system in the development of the GI tract and the progression of tumors within it. Meanwhile, the cancer cell-originated feedback regulation on the nervous system is revealed to play a crucial role in the growth and development of nerve cells within tumor tissues. This interaction is vital for understanding the complex relationship between the nervous system and GI oncogenesis. Additionally, the study identified various components within the TME that possess a significant influence on the occurrence and progression of GI cancer, including microbiota, immune cells, and fibroblasts. Moreover, we highlighted the transformation relationship between non-neuronal cells and neuronal cells during GI cancer progression, inspiring the development of strategies for nervous system-guided anti-tumor drugs. By further elucidating the deep mechanism of various neuroregulatory signals and neuronal intervention, we underlined the potential of these targeted drugs translating into effective therapies for GI cancer treatment. In summary, this review provides an overview of the mechanisms of neuromodulation and explores potential therapeutic opportunities, providing insights into the understanding and management of GI cancers.
    DOI:  https://doi.org/10.1038/s41388-023-02909-x
  2. Front Neurosci. 2023 ;17 1321176
      Chronic stress has a substantial influence on the tumor microenvironment (TME), leading to compromised effectiveness of anti-cancer therapies through diverse mechanisms. It disrupts vital functions of immune cells that play a critical role in anti-tumor immunity, such as the inhibition of dendritic cells (DCs) and lymphocytes, while simultaneously enhancing the activity of immune cells that support tumor growth, such as myeloid-derived suppressor cells and tumor-associated macrophages. Furthermore, chronic stress exerts a significant impact on crucial mechanisms within the TME, including angiogenesis, DNA repair, hypoxia, extracellular matrix deposition, and tumor metabolism. These alterations in the TME, induced by stress, result from the activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, in conjunction with epigenetic modifications. In conclusion, chronic stress significantly influences the TME and impedes the efficacy of anti-cancer treatments, underscoring the importance of targeting stress pathways to improve therapeutic results.
    Keywords:  HPA axis; anticancer treatments; chronic stress; immunotherapy; neural-immune interactions; personalized medicine; sympathetic nervous system; tumor microenvironment
    DOI:  https://doi.org/10.3389/fnins.2023.1321176
  3. World J Clin Cases. 2023 Nov 06. 11(31): 7673-7679
       BACKGROUND: Malignant schwannoma is a rare tumor in the peripheral nervous system, accounting for approximately 5% to 10% of systemic soft tissue sarcomas. Especially, malignant schwannoma occurring in the broad ligament of the uterus with hemophilic syndrome and bone marrow fibrosis is extremely rare in clinical practice. Here, we report the first case of an patient diagnosed with malignant peripheral nerve sheath tumor (MPNST) of the broad ligament of the uterus with hemophilic syndrome and bone marrow fibrosis, and share our reference clinical diagnosis and treatment experience.
    CASE SUMMARY: A patient was diagnosed with MPNST of the uterus harboring hemophilic syndrome and bone marrow fibrosis. She received combination, and repeated imaging revealed further encountered rare complications (hemophilia syndrome and bone marrow fibrosis) after two cycles of chemotherapy. Thereafter, combined treatment with pazopanib, gemcitabine, and dacarbazine was initiated. Unfortunately, the patient succumbed to death at hospital after two weeks.
    CONCLUSION: This report firstly provided reference clinical practice for a patient with MPNST of the uterus harboring hemophilic syndrome and bone marrow fibrosis. Our case raises a reminder about the tolerance and safety of combination therapy, especially in young women.
    Keywords:  Bone marrow fibrosis; Case report; Hemophilic syndrome; Malignant peripheral nerve sheath tumor
    DOI:  https://doi.org/10.12998/wjcc.v11.i31.7673
  4. J Med Case Rep. 2023 Dec 11. 17(1): 538
       BACKGROUND: Schwannomas are solitary well-circumscribed encapsulated benign tumors that exhibit Schwann cell differentiation, and arise directly from myelinated peripheral or central nerves. Although they are usually asymptomatic and found incidentally, schwannomas can cause symptoms due to compression of nearby structures which, depending on the location, can make clinical presentations widely variable. Despite their rarity, schwannomas have been documented in a number of locations including the limbs, cerebellopontine angle, posterior mediastinum, and, far more infrequently, the lungs.
    CASE PRESENTATION: In this article, we report an incidental finding of an intrapulmonary schwannoma in a 59-year-old Pakistani woman who was grossly asymptomatic upon presentation to the cardiothoracic surgery clinic. An [18F]fluorodeoxyglucose positron emission tomography/computed tomography scan revealed a lobulated soft-tissue lesion measuring 23 mm × 23 mm in the lower lobe of the right lung. A computed tomography-guided core biopsy of the mass was performed, which revealed a benign spindle cell lesion based on histopathological examination and immunohistochemical staining. The mass was surgically resected via a right lower lobectomy, and subsequently confirmed to be an encapsulated neoplastic lesion composed of well-differentiated Schwann cells. There were no short- or long-term complications, morbidities, or recurrences based on 1-year follow-up.
    CONCLUSION: This report underscores the predominantly asymptomatic nature of schwannomas and reemphasizes the efficacy of surgical resection as a safe and curative procedure for a tumor of this nature. Albeit very rare, intrapulmonary schwannomas can be considered a differential diagnosis when encountering solitary asymptomatic pulmonary nodules or masses.
    Keywords:  Atypical schwannoma; Lobectomy; Neoplasm
    DOI:  https://doi.org/10.1186/s13256-023-04234-z
  5. J Comput Assist Tomogr. 2023 Dec 12.
       OBJECTIVE: This study aimed to assess the usefulness of magnetic resonance imaging (MRI) findings for differentiating low-grade and high-grade malignant peripheral nerve sheath tumors (MPNSTs).
    METHODS: This study included 31 patients (onset age range, 19-83 years; mean onset age, 57 years; 9 men and 22 women) with 36 histopathologically proven MPNSTs (7 low-grade MPNSTs and 29 high-grade MPNSTs) who underwent preoperative MRI between December 2007 and October 2022. Quantitative and qualitative MRI findings were retrospectively evaluated and compared between the 2 subtypes.
    RESULTS: The maximum tumor diameter (106.1 ± 64.0 vs 54.9 ± 19.8 mm, P = 0.032) and tumor-to-muscle signal intensity ratio (SIR) of fat-suppressed gadolinium-enhanced T1-weighted images (2.69 ± 1.40 vs 1.62 ± 0.40, P = 0.005) were significantly higher in high-grade MPNSTs than in low-grade MPNSTs. The receiver operating characteristic analysis revealed that the tumor-to-muscle SIR of fat-suppressed gadolinium-enhanced T1-weighted images exhibited the highest area under the curve value (0.88), followed by the maximum tumor diameter (0.76). The sensitivity and specificity of the tumor-to-muscle SIR of fat-suppressed gadolinium-enhanced T1-weighted images for diagnosing high-grade MPNST at an optimal SIR threshold of greater than 1.73 were 90% and 83%, respectively. However, other MRI findings showed no significant differences between the 2 subtypes (P = 0.16-1.00).
    CONCLUSIONS: Although the MRI findings of low-grade and high-grade MPNST overlapped considerably, the maximum tumor diameter and degree of contrast enhancement can be used to differentiate low-grade MPNST from high-grade MPNST.
    DOI:  https://doi.org/10.1097/RCT.0000000000001569
  6. J Bone Oncol. 2023 Dec;43 100510
      Cancer-induced bone pain (CIBP) is the most common and devastating symptom of bone metastatic cancer that substantially disrupts patients' quality of life. Currently, there are few effective analgesic treatments for CIBP other than opioids which come with severe side effects. In order to better understand the factors and mechanisms responsible for CIBP it is essential to have clinically relevant animal models that mirror pain-related symptoms and disease progression observed in patients with bone metastatic cancer. In the current study, we characterize a syngeneic mouse model of prostate cancer induced bone pain. We transfected a prostate cancer cell line (RM1) with green fluorescent protein (GFP) and luciferase reporters in order to visualize tumor growth longitudinally in vivo and to assess the relationship between sensory neurons and tumor cells within the bone microenvironment. Following intra-femoral injection of the RM1 prostate cancer cell line into male C57BL/6 mice, we observed a progressive increase in spontaneous guarding of the inoculated limb between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. Daily running wheel performance was evaluated as a measure of functional impairment and potentially movement evoked pain. We observed a progressive reduction in the distance traveled and percentage of time at optimal velocity between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. We utilized histological, radiographic and μCT analysis to examine tumor induced bone remodeling and observed osteolytic lesions as well as extra-periosteal aberrant bone formation in the tumor bearing femur, similar to clinical findings in patients with bone metastatic prostate cancer. Within the tumor bearing femur, we observed reorganization of blood vessels, macrophage and nerve fibers within the intramedullary space and periosteum adjacent to tumor cells. Tumor bearing mice displayed significant increases in the injury marker ATF3 and upregulation of the neuropeptides SP and CGRP in the ipsilateral DRG as well as increased measures of central sensitization and glial activation in the ipsilateral spinal cord. This immunocompetent mouse model will be useful when combined with cell type selective transgenic mice to examine tumor, immune cell and sensory neuron interactions in the bone microenvironment and their role in pain and disease progression associated with bone metastatic prostate cancer.
    Keywords:  Bone metastasis; Malignant bone pain; Nociceptor; Oncology
    DOI:  https://doi.org/10.1016/j.jbo.2023.100510
  7. J Pain Res. 2023 ;16 4181-4189
      Cancer-related pain is one of the most common and incapacitating symptoms for cancer patients. Cancer pain can be caused by diagnostic or therapeutic procedures, side effects and toxicity from therapy, or the cancer itself. Uncontrolled cancer-related pain is associated with inadequate quality of life and reduced functional status. Optimal pain management during the perioperative period requires a tailored approach. Interventions that are recommended for the management of acute surgical pain include regional anesthesia, local anesthetic infusions, non-opioid analgesics (ketamine, dexmedetomidine, lidocaine, and non-steroidal anti-inflammatory drugs), and opioids. Despite continued research efforts and advances in cancer treatment, opioids remain the most effective medication to treat moderate to severe cancer-related pain; however, their role has been changing significantly due to the opioid epidemic and opioid misuse. While pre-clinical and retrospective studies have shown a negative association between opioid use and cancer outcomes, randomized control trials have failed to confirm this association. The purpose of this review is to summarize the pharmacological management of acute cancer-related pain during the perioperative period with an emphasis on cancer recurrence.
    Keywords:  cancer; cancer progression; dexmedetomidine; ketamine; lidocaine; multimodal analgesia; opioids; overall survival; pain; progression free-survival
    DOI:  https://doi.org/10.2147/JPR.S432444
  8. bioRxiv. 2023 Nov 29. pii: 2023.11.29.569123. [Epub ahead of print]
      Malignant peripheral nerve sheath tumor (MPNST) is a rare, aggressive soft-tissue sarcoma with a poor prognosis and is insensitive to immune checkpoint blockade (ICB) therapy. Loss-of-function of the histone modifying polycomb repressive complex 2 (PRC2) components, EED or SUZ12, is one of the main mechanisms of malignant transformation. In a murine model of MPNST, PRC2-loss tumors have an "immune desert" phenotype and intratumoral (IT) delivery immunogenic modified vaccinia virus Ankara (MVA) sensitized the PRC2-loss tumors to ICB. Here we show that IT MQ833, a second-generation recombinant modified vaccinia virus Ankara virus, results in neutrophil recruitment and activation and neutrophil-dependent tumor killing in the MPNST model. MQ833 was engineered by deleting three viral immune evasion genes, E5R, E3L, and WR199, and expressing three transgenes, including the two membrane-bound Flt3L and OX40L, and IL-12 with an extracellular matrix anchoring signal. Furthermore, we explored strategies to enhance anti-tumor effects of MQ833 by co-administration of granulocyte colony-stimulating factor (G-CSF).
    DOI:  https://doi.org/10.1101/2023.11.29.569123
  9. Auton Neurosci. 2023 Dec 06. pii: S1566-0702(23)00065-6. [Epub ahead of print]251 103136
      Cancer cachexia, characterized by muscle wasting and widespread inflammation, poses a significant challenge for patients with cancer, profoundly impacting both their quality of life and treatment management. However, existing treatment modalities remain very limited, accentuating the necessity for innovative therapeutic interventions. Many recent studies demonstrated that changes in autonomic balance is a key driver of cancer cachexia. This review consolidates research findings from investigations into autonomic dysfunction across cancer cachexia, spanning animal models and patient cohorts. Moreover, we explore therapeutic strategies involving adrenergic receptor modulation through receptor blockers and agonists. Mechanisms underlying adrenergic hyperactivity in cardiac and adipose tissues, influencing tissue remodeling, are also examined. Looking ahead, we present a perspective for future research that delves into autonomic dysregulation in cancer cachexia. This comprehensive review highlights the urgency of advancing research to unveil innovative avenues for combatting cancer cachexia and improving patient well-being.
    Keywords:  Adipose tissue innervation; Autonomic dysfunction; Beta blockers; Cardiac innervation; Heart rate variability; Skeletal muscle; Sympathetic signaling; cancer cachexia
    DOI:  https://doi.org/10.1016/j.autneu.2023.103136
  10. Nutrients. 2023 Nov 28. pii: 4936. [Epub ahead of print]15(23):
      Alterations in the central nervous system in cancer patients are pivotal in determining appetite dysregulation and body weight loss (BWL). Autonomic nervous system activity was tested by measuring heart rate variability (HRV) in cancer patients presenting with anorexia. We considered inpatients with different types of cancer and investigated anorexia using their FAACT scores. HRV was evaluated by a three-channel Holter ECG. The domains of low frequencies (LF, sympathetic activity) and high frequencies (HF, parasympathetic activity) were calculated. Also, SDNN (autonomic activity) and RMSSD (parasympathetic activity) were assessed. We enrolled 56 patients with cancer and 23 controls. In cancer patients, RMSSD and SDNN were lower than in controls (p < 0.001 and p = 0.009). Sympathetic activity (LF nu) was lower in cancer patients than in controls (p = 0.023), including sympathovagal balance (LF/HF nu ratio) (p = 0.025). RMSSD was reduced in anorexic (p < 0.001) and non-anorexic (p = 0.003) cancer patients compared to controls. The SDNN was lower in anorexic cancer patients than in non-anorexic cancer patients (p = 0.025), and it was lower in anorexic cancer patients than in controls (p = 0.001). LF nu was lower in anorexic cancer patients than in controls (p = 0.015), as was LF/HF (p = 0.031). SDNN was negatively correlated with BWL in the cancer group (rho = -0.40; p = 0.007). Our data support the hypothesis that autonomic nervous system dysregulation exists in patients with cancer presenting with anorexia, with implications for its diagnosis and treatment.
    Keywords:  autonomic nervous system; body weight loss; cancer anorexia; heart rate variability; malnutrition
    DOI:  https://doi.org/10.3390/nu15234936
  11. Cancer Innov. 2023 Oct;2(5): 433-437
      Retroperitoneal ganglioneuroma is a rare benign tumor that is challenging in terms of clinical diagnosis. Computed tomography and magnetic resonance imaging are usually performed for diagnosis rather than convenient and inexpensive ultrasonography. Here, we present the case of a 21-year-old female patient who was diagnosed by multimodal ultrasound imaging and whose diagnosis was confirmed by ultrasound-guided core needle biopsy before surgery. We hope that this rare case will help clinicians and radiologists realize the advantages of multimodal ultrasound imaging in the diagnosis of retropeitoneal solid tumors, and reduce misdiagnosis.
    Keywords:  diagnosis; ganglioneuroma; retroperitoneal mass; ultrasonography
    DOI:  https://doi.org/10.1002/cai2.73
  12. Clin Med Insights Case Rep. 2023 ;16 11795476231215907
      Primary hepatic schwannoma is an extremely rare tumor with a good prognosis. Preoperative diagnosis is often challenging due to nonspecific clinical symptoms and its rarity. Here, we report a case of a 56-year-old male patient misdiagnosed with malignant liver tumor, later identified as primary hepatic schwannoma. Furthermore, clinical and histopathological features of 19 cases of primary hepatic schwannoma are also documented. The age of the patients ranged from 38 to 72 years, with a mean age of 56.4 years, and the disease was more common in females. Patients typically presented without clinical symptoms and were not associated with neurofibromatosis type 1. Histopathological features of the tumor were similar to soft tissue schwannoma, characterized by a thick capsule consisting of Antoni A and Antoni B areas. Immunohistochemically, the tumor showed strong positivity and diffusely stained with S-100, while being negative for CD34, CD117, and SMA. Complete resection of the tumor was achieved in all patients. The prognosis was favorable, with no signs of recurrence. Follow-up examinations revealed disease-free survival ranging from 6 to 27 months. Differential diagnosis of primary hepatic schwannoma from malignant liver tumors and metastatic liver tumors can be made based on histopathological features and immunohistochemical staining with S-100.
    Keywords:  Computed tomography; hepatic schwannoma; liver resection; liver tumor; neurofibromatosis
    DOI:  https://doi.org/10.1177/11795476231215907
  13. Front Oncol. 2023 ;13 1295267
      Immunotherapy has revolutionized treatments for both early and advanced cancers, and as their role evolves, their impact on sleep and circadian rhythms continues to unfold. The recognition, evaluation, and treatment of sleep and circadian rhythm disturbance leads to improved symptom management, quality of life and treatment outcomes. An intricate complex relationship exists in the microenvironment with immunity, sleep and the tumor, and these may further vary based on the cancer, addition of standard chemotherapy, and pre-existing patient factors. Sleep and circadian rhythms may offer tools to better utilize immunotherapy in the care of cancer patients, leading to better treatment outcome, reduced symptom burden, and increased quality of life.
    Keywords:  circadian rhythm; immune checkpoint inhibitors; immunity; immunotherapy; sleep
    DOI:  https://doi.org/10.3389/fonc.2023.1295267