bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2023–06–25
eight papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute
  1. Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma.
  2. Nerve terminals in the tumor microenvironment as targets for local infiltration analgesia.
  3. A Review on the Neurotoxic Effects of Doxorubicin.
  4. Predictors for the Development of Neurological Immune-related Adverse Events of Immune Checkpoint Inhibitors and Impact on Mortality.
  5. Giant lumbar schwannoma with retroperitoneal extension and vertebral body invasion: a case report.
  6. Malignant Peripheral Nerve Sheath Tumor of the Hand: A Case Report.
  7. Nerve sheath tumor in the forearm of a common marmoset (Callithrix jacchus).
  8. An Unusual Case of Schwann Cell Hamartoma in Colon.
  1. Neurosci Bull. 2023 Jun 22.
    Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma.
    Bo Ni, Yiqing Yin, Zekun Li, Junjin Wang, Xiuchao Wang, Kaiyuan Wang.
      Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy, characterized by late diagnosis, aggressive growth, and therapy resistance, leading to a poor overall prognosis. Emerging evidence shows that the peripheral nerve is an important non-tumor component in the tumor microenvironment that regulates tumor growth and immune escape. The crosstalk between the neuronal system and PDAC has become a hot research topic that may provide novel mechanisms underlying tumor progression and further uncover promising therapeutic targets. In this review, we highlight the mechanisms of perineural invasion and the role of various types of tumor innervation in the progression of PDAC, summarize the potential signaling pathways modulating the neuronal-cancer interaction, and discuss the current and future therapeutic possibilities for this condition.
    Keywords:  Cancer-neuroscience; PDAC; Pain; Peripheral innervation
    DOI:  https://doi.org/10.1007/s12264-023-01082-1
  2. Neurosci Res. 2023 Jun 17. pii: S0168-0102(23)00111-6. [Epub ahead of print]
    Nerve terminals in the tumor microenvironment as targets for local infiltration analgesia.
    Pallavi Madhusudanan, Chinnu Jerard, Gayathri Raju, Neeraj Katiyar, Sahadev A Shankarappa.
      Nerve terminals within the tumor microenvironment as potential pain-mitigating targets for local infiltration analgesia is relatively less explored. In this study, we examine the role of key analgesics administered as local infiltration analgesia in a model of cancer-induced bone pain (CIBP). CIBP was induced by administration of allogenic MRMT1 breast cancer cells in the proximal tibia of rats, and tumor mass characterized using radiogram, micro-CT, and histological analysis. In vitro responsiveness to key analgesics δ-opioid receptor agonist (DOPr), Ca2+ channel and TRPV1 antagonists was assessed using ratiometric Ca2+ imaging in sensory neurons innervating the tumor site. Effectiveness of locally infiltrated analgesics administered independently or in combination was assessed by quantifying evoked limb withdrawal thresholds at two distinct sites for up to 14 days. CIBP animals demonstrated DOPr, N-, and L-type and TRPV1 expression in lumbar dorsal root ganglion neurons (DRG), comparable to controls. Evoked Ca2+ transients in DRG neurons from CIBP animals were significantly reduced in response to treatment with compounds targeting DOPr, N-, L-type Ca2+ channels and TRPV1 proteins. Behaviourally, evoked hyperalgesia at the tumor site was strongly mitigated by peritumoral injection of the DOPr agonist and T-type calcium antagonist, via its activity on bone afferents. Results from this study suggest that nerve terminals at tumor site could be utilized as targets for specific analgesics, using local infiltration analgesia.
    Keywords:  TRPV1; analgesia; calcium channel; cancer pain; hyperalgesia; innervation; opioids
    DOI:  https://doi.org/10.1016/j.neures.2023.06.006
  3. Neurotox Res. 2023 Jun 23.
    A Review on the Neurotoxic Effects of Doxorubicin.
    Katarzyna Kamińska, Agnieszka Cudnoch-Jędrzejewska.
      Anthracyclines, a class of drugs considered as most effective anticancer drugs, used in the various regimens of cancer chemotherapy, induce long-term impairment of mitochondrial respiration, increase reactive oxygen species, and induce other mechanisms potentially leading to neurotoxicity. According to literature findings, one drug of this class - doxorubicin used to treat e.g. breast cancer, bladder cancer, lymphoma, and acute lymphocytic leukemia may induce such effects in the nervous system. Doxorubicin has poor penetration into the brain due to the lack of drug penetration through the blood-brain barrier, thus the toxicity of this agent is the result of its peripheral action. This action is manifested by cognitive impairment and anatomical changes in the brain and peripheral nervous system found in both preclinical and clinical studies in adult patients. Furthermore, more than 50% of children with cancer are treated with anthracyclines including doxorubicin, which may affect their nervous system, and lead to lifelong damage in many areas of their life. Despite ongoing research into the side effects of this drug, the mechanism of its neurotoxicity action on the central and peripheral nervous system is still not well understood. This review aims to summarize the neurotoxic effects of doxorubicin in preclinical (in vitro and in vivo) research and in clinical studies. Furthermore, it discusses the possible mechanisms of the toxic action of this agent on the nervous system.
    Keywords:  Central nervous system; Chemotherapeutic drug; Doxorubicin; Neurotoxicity
    DOI:  https://doi.org/10.1007/s12640-023-00652-5
  4. Eur J Neurol. 2023 Jun 23.
    Predictors for the Development of Neurological Immune-related Adverse Events of Immune Checkpoint Inhibitors and Impact on Mortality.
    Chen Yan, Merry Huang, Carol Swetlik, Karlo Toljan, Ahmad Z Mahadeen, James Bena, Amy Kunchok, Pauline Funchain, Marisa McGinley.
       BACKGROUND: Little is known about risk factors for developing neurological immunological adverse events (neuro-irAEs) from immune check point inhibitors (ICI). We report the incidence, predictors for development, impact on mortality of neuro-irAEs, and impact of ICI on pre-existing neurological conditions in a large clinical cohort.
    METHODS: Patients who received ICI between January 2011 and December 2018 were identified from a tertiary cancer center registry. Descriptive statistics were used to summarize patient, cancer, and treatment data. Odds ratios from univariable and multivariable logistic regression models were calculated to identify potential predictors for developing a neuro-irAE. Impact of neuro-irAE on overall survival was estimated by Kaplan-Meier and Cox proportional-hazard models.
    RESULTS: Overall frequency of neurological irAEs was 2.3%. Peripheral nervous system complications were most frequent (53.6%). Melanoma, younger age, prior chemotherapy, prior resection, CTLA-4 ICI exposure, and combination PD-1 and CTLA-4 ICI exposure had significantly higher odds for developing a neuro-irAE (p <0.05) on univariate but not multivariate models. Those with a neuro-irAE were less likely to die at 3 years compared to those without a neuro-irAE (69% vs 55%, p=0.004) in univariate but not multivariate model. Flare of pre-existing neurological condition after exposure to ICI was present (15.4%, 2 of 13 patients) but manageable. One patient was rechallenged with ICI without recurrent flare.
    CONCLUSIONS: Neuro-irAEs are not associated with increase in overall mortality. Potential predictors for the development of neuro irAEs are younger age, melanoma, prior chemotherapy and resection, CTLA-4, or combination ICI exposure.
    Keywords:  immune checkpoint inhibitors; incidence; mortality; risk factors
    DOI:  https://doi.org/10.1111/ene.15942
  5. Pan Afr Med J. 2023 ;44 140
    Giant lumbar schwannoma with retroperitoneal extension and vertebral body invasion: a case report.
    Angky Saputra, Joshua Sutikno, Raka Janitra, Erliano Sufarnap, Centery, Roslan Yusni Hasan, Satyanegara, Harviandi Sumarsudi, Franky Yesaya Siahaan, Komaruddin Boenjamin.
      Schwannoma is a type of peripheral nerve sheath tumor derived from Schwann cells. There have been only a few cases of giant lumbar schwannoma with retroperitoneal extension eroding the vertebral body documented. Thus, managing these tumors presents various challenges. This paper reports a case of a 59-year-old woman who experienced lower back radicular pain for a year. A lumbar magnetic resonance imaging revealed the presence of a giant extradural soft tissue tumor measuring 8.6x7.4x9.7 cm, compressing the right L5-S1 neural foramen and extending into the retroperitoneal space while eroding the L5 vertebral body. The patient underwent surgery via a retroperitoneal approach, and the tumor was successfully resected. Histopathological examination confirmed the diagnosis of schwannoma. In conclusion, giant retroperitoneal lumbar schwannomas with bone invasion are rare, and gross total resection is the preferred treatment option, but the size and location of the tumor can make the surgery challenging.
    Keywords:  Schwannoma; case report; lumbar spine; retroperitoneal; surgery
    DOI:  https://doi.org/10.11604/pamj.2023.44.140.37717
  6. Cureus. 2023 May;15(5): e39205
    Malignant Peripheral Nerve Sheath Tumor of the Hand: A Case Report.
    Sangita Jogdand, Rahul Rajendran.
      An uncommon and aggressive type of soft tissue sarcoma that develops from peripheral nerves is known as a malignant peripheral nerve sheath tumor (MPNST). It is typically associated with neurofibromatosis type 1. Hence, this case report presents a case of a 42-year-old woman with a mass over the palmar aspect of her right hand that had been slowly growing over the previous year. Complete resection of the tumor with groin flap was performed followed by adjuvant radiotherapy. Over the last year, the patient has been monitored on an outpatient basis without displaying any signs of a local recurrence.
    Keywords:  hand tumor; malignant peripheral nerve sheath tumor; radiotherapy; sarcoma; solitary neurofibroma
    DOI:  https://doi.org/10.7759/cureus.39205
  7. J Med Primatol. 2023 Jun 20.
    Nerve sheath tumor in the forearm of a common marmoset (Callithrix jacchus).
    Sarah Kezar, Natalie W Fowlkes, Martha E Hensel.
      Tumors of the skin and subcutaneous tissues are uncommon in marmosets. In this report, we describe the gross, histopathology, and immunohistochemical findings of a nerve sheath tumor that arose in the left forearm of an adult female marmoset (Callthrix jacchus).
    Keywords:   Callithrix jacchus ; common marmoset; neoplasia; nerve sheath tumor; soft-tissue sarcoma
    DOI:  https://doi.org/10.1111/jmp.12659
  8. Cureus. 2023 May;15(5): e39301
    An Unusual Case of Schwann Cell Hamartoma in Colon.
    Sanna Salam, Hazem Abosheaishaa, Muhammad Haseeb Ul Rasool, Nimra Qasim, Ghullamullah Shahzad.
      Schwann cell tumors are benign tumors originating from Schwann cells of the peripheral nervous system and are extremely rare in the gastrointestinal system. They usually originate in the colon or rectum but can also occur in the esophagus and small intestine. Their occurrence is rare in GI tract and mainly in the sigmoid colon. Schwann cell tumors have no association with any familial cancer syndromes. We present a 65-year-old female patient who underwent routine colon cancer screening. In addition to open mouth diverticulosis, she was found to have a 3 mm polyp, which was diagnosed as a Schwann cell hamartoma after a biopsy. This study aimed to present this rarely reported case in the literature as an example of a tumor that should be included in the differential diagnosis when considering submucosal colonic lesions. Though the reported reoccurrence rate is low, this case highlights the lack of published guidelines regarding appropriate follow-up surveillance periods.
    Keywords:  bleeding per rectum; cancer colon; colonoscopy; polyp; schwann cell
    DOI:  https://doi.org/10.7759/cureus.39301
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