bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2023‒03‒26
eight papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

  1. Cell Biosci. 2023 Mar 20. 13(1): 60
      Prostate cancer (PC) represents the most diagnosed and the second most lethal cancer in men worldwide. Its development and progression occur in concert with alterations in the surrounding tumor microenvironment (TME), made up of stromal cells and extracellular matrix (ECM) that dynamically interact with epithelial PC cells affecting their growth and invasiveness. PC cells, in turn, can functionally sculpt the TME through the secretion of various factors, including neurotrophins. Among them, the nerve growth factor (NGF) that is released by both epithelial PC cells and carcinoma-associated fibroblasts (CAFs) triggers the activation of various intracellular signaling cascades, thereby promoting the acquisition of a metastatic phenotype. After many years of investigation, it is indeed well established that aberrations and/or derangement of NGF signaling are involved not only in neurological disorders, but also in the pathogenesis of human proliferative diseases, including PC. Another key feature of cancer progression is the nerve outgrowth in TME and the concept of nerve dependence related to perineural invasion is currently emerging. NGF released by cancer cells can be a driver of tumor neurogenesis and nerves infiltrated in TME release neurotransmitters, which might stimulate the growth and sustainment of tumor cells.In this review, we aim to provide a snapshot of NGF action in the interactions between TME, nerves and PC cells. Understanding the molecular basis of this dialogue might expand the arsenal of therapeutic strategies against this widespread disease.
    Keywords:  Nerve-growth factor; Perineural invasion; Prostate cancer; Tumor microenvironment
  2. Cancer Med. 2023 Mar 23.
      BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poorer prognosis in several human malignancies, but their significance in gastric cancer (GC) remains to be clearly defined. Our study aimed to investigate the prognostic value of LVI/PNI in patients with curative resected GC.METHODS: Records of 1488 patients with stage I--III GC and 3327 patients with stage I-III colorectal cancer (CRC) were reviewed retrospectively, and difference in the incidence of LVI/PNI between GC and CRC was compared. Univariate and multivariate analyses were used to evaluate whether LVI/PNI was an independent risk factor for lymph node metastasis (LNM) and overall survival (OS) in GC.
    RESULTS: Patients with stage I-III GC had a significantly higher incidence of LVI/PNI than patients with stage I-III CRC (50.54% vs. 21.91%, p  < 0.001). LVI/PNI was significantly associated with higher CEA, higher CA199, deeper tumor invasion, more lymph node metastasis, and advanced TNM stage in GC ( p  < 0.05). Multivariate logistic regression analysis identified LVI/PNI (OR = 2.64, 95%CI: 2.05-3.40, p  < 0.001) as an independent risk factor for LNM in GC. The OS rate was significantly lower in the LVI/PNI-positive GC group than that in the LVI/PNI-negative GC group ( p  < 0.001). On multivariate Cox regression analysis, LVI/PNI (HR = 1.34, 95%CI: 1.04-1.71, p  = 0.023) was an independent prognostic factor for OS in GC.
    CONCLUSION: GC has a high incidence of LVI/PNI, which was closely associated with disease progression. LVI/PNI could serve as an independent risk factor for LNM and the prognosis of patients with curative resected GC. These findings will be helpful in predicting survival outcomes more accurately and establishing individualized treatment plans.
    Keywords:  gastric cancer; lymph node metastasis; lymphovascular invasion; perineural invasion; prognosis
  3. Protein Cell. 2022 Jul 15. pii: pwac030. [Epub ahead of print]
      Neurons migrate from their birthplaces to the destinations, and extending axons navigate to their synaptic targets by sensing various extracellular cues in spatiotemporally controlled manners. These evolutionally conserved guidance cues and their receptors regulate multiple aspects of neural development to establish the highly complex nervous system by mediating both short- and long-range cell-cell communications. Neuronal guidance genes (encoding cues, receptors, or downstream signal transducers) are critical not only for development of the nervous system but also for synaptic maintenance, remodeling, and function in the adult brain. One emerging theme is the combinatorial and complementary functions of relatively limited classes of neuronal guidance genes in multiple processes, including neuronal migration, axonal guidance, synaptogenesis, and circuit formation. Importantly, neuronal guidance genes also regulate cell migration and cell-cell communications outside the nervous system. We are just beginning to understand how cells integrate multiple guidance and adhesion signaling inputs to determine overall cellular/subcellular behavior and how aberrant guidance signaling in various cell types contributes to diverse human diseases, ranging from developmental, neuropsychiatric, and neurodegenerative disorders to cancer metastasis. We review classic studies and recent advances in understanding signaling mechanisms of the guidance genes as well as their roles in human diseases. Furthermore, we discuss the remaining challenges and therapeutic potentials of modulating neuronal guidance pathways in neural repair.
    Keywords:  angiogenesis; axon guidance; cancer metastasis; cell-cell communications; neural circuit formation; neural mapping; neuronal migration; organogenesis; synaptogenesis
  4. Cancer Biomark. 2023 Mar 09.
      BACKGROUND: Abdominal or back pain is a common symptom in pancreatic diseases. However, the role of pain in pancreatic neuroendocrine neoplasm (PNENs) has not been clarified.OBJECTIVE: In this study, we aimed to show the association between the pain and the grade of PNENs.
    METHODS: A total of 186 patients with pathologically confirmed PNENs were included in this study. Clinical features and histological or radiological findings (size, location, and vascular invasion and local organs invasion and distal metastasis) were collected. Logistic regression analyses were used to show the association between pain and grade of PNENs. Nomogram was developed based on associated factors to predict the higher grade of PNENs. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of size and nomogram model.
    RESULTS: The prevalence of pain in the cohort was 30.6% (n= 57). The vascular invasion and G3 PNENs were more common in the pain group (P= 0.02, P< 0.01). The tumor size was larger and incident of higher grade of PNENs was higher in the pain group than the non-pain group (p< 0.01). Age, pain and size were independent risk factors for G2/G3 or G3 PNENs. The odds ratio was 3.03 (95% CI: 1.67-7.91) and 3.32 (95% CI: 1.42-7.79) for pain, respectively. The nomogram model was developed to predict the G2/G3 or G3 PNENs. The area under the curve (AUC) of the nomogram model was 0.84 (95% CI, 0.77-0.91) in predicting the G2/G3 PNENs, and was 0.84 (95% CI, 0.78-0.91) in predicting the G3 PNENs.
    CONCLUSION: Abdominal or back pain is associated with the grade of PNENs. The nomograms based on clinical features may be a powerful numerical tool for predicting the grade of PNENs.
    Keywords:  Pancreatic neuroendocrine neoplasm; clinical features; grade; nomogram; pain
  5. BMJ Case Rep. 2023 Mar 21. pii: e254970. [Epub ahead of print]16(3):
      Schwannomas are nerve sheath tumours that can be found throughout the body along peripheral nerves. Primary schwannomas of the colon are very rare. They are usually benign and their surgical resection is considered curative. They are, however, difficult to diagnose preoperatively and therefore tend to be overtreated with major colorectal surgery.
    Keywords:  Colon cancer; Endoscopy; Gastrointestinal surgery; Radiology
  6. Cancer Med. 2023 Mar 23.
      BACKGROUND: Distal extrahepatic bile duct (EHBD) cancer is highly recurrent. More than 50% of patients suffer from disease relapse after curative resection. Some patients present with oligo-recurrence which could be a single loco-regional mass or lesions limited to a single solid organ. The aim of this study was to examine the effect of local control (surgical resection or radiofrequency ablation) on survival outcomes in patients with oligo-recurrent distal EHBD cancer.METHODS: Data of 1219 patients who underwent surgery for distal EHBD cancer from 2000 to 2018 were retrospectively reviewed. Clinicopathological characteristics and survival outcomes of patients with recurrence were investigated. Post-recurrence survival (PRS) was analyzed according to modalities of re-treatment (local treatment or systemic therapy alone).
    RESULTS: Among 654 patients with recurrence, 90 patients who had oligo-recurrence showed better recurrence-free and overall survival than patients with non-oligo-recurrent disease. Lymph node ratio and perineural invasion at initial pathology, timing of recurrence, and platelet-to-lymphocyte ratio at recurrence were independent risk factors for PRS in the oligo-recurrent group. Patients with local treatment for oligo-recurrence had better 3- and 5-year PRS than those with systemic treatment alone (38.3% vs. 14.1%, p = 0.04; 28.3% vs. 7.1%, p = 0.04, respectively). Recurrence within 24 months after initial surgery was the only significant factor for PRS in the local treatment group.
    CONCLUSION: In patients with oligo-recurrence after resection of distal EHBD cancer, post-recurrence local treatment could improve survival outcomes, particularly for those with recurrence more than 2 years after initial resection.
    Keywords:  bile duct cancer; cholangiocarcinoma; oligo-recurrence; recurrence; survival
  7. Int Med Case Rep J. 2023 ;16 141-151
      Schwannoma is a slowly growing benign tumor that arises from Schwann cells. Schwannomas affect both genders equally. It occurs in any age group, but most cases are seen between the third and fifth decade. About one-fourth to one-third of extracranial schwannomas cases originate in the head and neck region. The vagus nerve, followed by the cervical sympathetic chain, is the leading site of origin in the neck region. The majority of patients with schwannomas are asymptomatic. Patients with vagal nerve schwannomas in the neck primarily present with hoarseness of voice due to paralysis of the vocal cords. Because of their rarity and the lack of a neurologic deficit as a presenting symptom, preoperative consideration of schwannomas is tough, and several differential diagnoses may be entertained.The mainstay of treatment for vagal nerve schwannoma is complete surgical excision. Here we present a rare case of cervical vagal nerve schwannoma in a 30-year-old male farmer from Ethiopia. The patient presented with a gradually increasing neck swelling of 10 years duration. He started to have hoarseness in his voice five months prior to his presentation. On examination, he had a huge anterior neck swelling. He had two FNAC results, which were inconclusive, and a neck CT. With the consideration of multinodular goiter versus spindle cell neoplasm, the neck was explored, and complete excision of the mass was done. The excisional biopsy turned out to be a classical cervical schwannoma. So this report aims to make physicians aware of the rare case of schwannomas, particularly vagal nerve schwannomas. Clinicians should consider schwannomas in the differential diagnosis of a patient presenting with a cervical mass. Furthermore, they need to be well aware of the diagnostic workup, mainly the imaging modalities, which are essential for proper preoperative planning, surgical treatment, and postoperative complications of cervical schwannomas.
    Keywords:  cervical mass; neck mass; neurilemmoma; schwannoma; vagal nerve schwannoma
  8. Brain Behav Immun. 2023 Mar 18. pii: S0889-1591(23)00070-3. [Epub ahead of print]
      Insulin growth factor-1 (IGF-1), an osteoclast-dependent osteolysis biomarker, contributes to metastatic bone cancer pain (MBCP), but the underlying mechanism is poorly understood. In mice, the femur metastasis caused by intramammary inoculation of breast cancer cells resulted in IGF-1 increase in femur and sciatic nerve, and IGF-1-dependent stimulus/non-stimulus-evoked pain-like behaviors. Adeno-associated virus-based shRNA selective silencing of IGF-1 receptor (IGF-1R) in Schwann cells, but not in dorsal root ganglion (DRG) neurons, attenuated pain-like behaviors. Intraplantar IGF-1 evoked acute nociception and mechanical/cold allodynia, which were reduced by selective IGF-1R silencing in DRG neurons and Schwann cells, respectively. Schwann cell IGF-1R signaling promoted an endothelial nitric oxide synthase-mediated transient receptor potential ankyrin 1 (TRPA1) activation and release of reactive oxygen species that, via macrophage-colony stimulating factor-dependent endoneurial macrophage expansion, sustained pain-like behaviors. Osteoclast derived IGF-1 initiates a Schwann cell-dependent neuroinflammatory response that sustains a proalgesic pathway that provides new options for MBCP treatment.