bims-netuvo 2024-12-15 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2024–12–15
seven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Establishment and analysis of a prognostic model of pancreatic ductal adenocarcinomas based on nerve-cancer crosstalk-related genes.
Nerve autofluorescence to enhance nerve visualization during axillary lymph node dissection in three breast cancer patients: Case series.
MMP9: Link between neuropathy and colorectal cancer?
Chemotherapy-Induced Neuropathy Affecting the Gastrointestinal Tract.
Organoids in lung cancer brain metastasis: Foundational research, clinical translation, and prospective outlooks.
Extraneural Soft Tissue Perineurioma: A Report of a Rare Case of Peripheral Nerve Sheath Tumor.
Combined Ganglioneuroma-Schwannoma of the Retroperitoneum: An Exceedingly Rare Hybrid Nerve Sheath-Ganglioneural Tumor.

Int J Clin Exp Pathol. 2024 ;17(11): 396-410

Establishment and analysis of a prognostic model of pancreatic ductal adenocarcinomas based on nerve-cancer crosstalk-related genes.

Lei Jiang, Xiaozhi Lu, Yuran Dai, Kuirong Jiang, Yi Miao, Jun Yu, Lingdi Yin, Jishu Wei.

  Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a five-year survival rate of 13%, the lowest among all malignant tumors. The work aims to use bioinformatics methods to mine Nerve-cancer crosstalk-related genes (NCCGs) in pancreatic cancer and evaluate their correlation with tumor stage and prognosis, thereby providing a new direction of development and experimental basis for pancreatic cancer treatment. This study included 185 individuals with PDAC from the TCGA database, together with clinical and RNA sequencing data. A review of prior studies revealed the mechanism of neural-cancer crosstalk and identified 42 neural-cancer crosstalk-related genes (NCCGs). Multivariate logistic regression analysis showed that NGFR (OR=39.076, 95% CI; P<0.05), CHRNB2 (OR=41.076, 95% CI; P<0.05), and CHRNA10 (OR=39.038, 95% CI; P<0.05) were identified as independent risk factors for PNI development. Pearson correlation analysis revealed that CHRNA10 was negatively connected with PDAC microsatellite instability, whereas CHRNA10, CHRNB2, and NGFR were negatively correlated with PDAC tumor mutation burden. The GEPIA database revealed that CHRNB2 expression was higher in stage I PDAC. The pancreatic cancer single-cell dataset PAAD_CRA001160 revealed that malignant tumor cells, ductal cells, endothelial cells and fibroblasts accounted for a large proportion in the tumor microenvironment of pancreatic cancer. Furthermore, the NGFR gene was shown to be more significantly expressed in various pancreatic cancer cells. Bioinformatics analysis was used to create a validated prognostic model of pancreatic cancer, which explored the critical mechanisms of neural-tumor interactions and revealed the potential of cancer-neural crosstalk-related genes as prognostic biomarkers and anti-tumor therapy targets.

Keywords:  Pancreatic ductal adenocarcinoma; bioinformatics analysis; cancer-neural crosstalk-related genes; prognostic model

DOI:  https://doi.org/10.62347/GHUM8504
Int J Surg Case Rep. 2024 Dec 09. pii: S2210-2612(24)01504-9. [Epub ahead of print]126 110723

Nerve autofluorescence to enhance nerve visualization during axillary lymph node dissection in three breast cancer patients: Case series.

Nicola Rocco, Nunzio Velotti, Maurizio Bruno Nava, Giuseppe Catanuto, Mafalda Ingenito, Mario Musella.

   INTRODUCTION AND IMPORTANCE: Iatrogenic nerve injury is a possible complication of axillary lymph node dissection (ALND), which remains standard-of-care for some breast cancer patients. Recently, several studies have demonstrated that nerves auto-fluoresce in near-ultraviolet light (NUVL). We describe three women with BC in whom a recently-developed NUVL camera was used to facilitate visualization of and prevent iatrogenic injury to the intercostobrachial, long thoracic, and thoracodorsal nerves during ALND.
CASE PRESENTATION: In all three women, ALND was deemed necessary per current guidelines for the treatment of locally-advanced breast cancer following neoadjuvant chemotherapy. The surgery was performed using standard-of-care surgical techniques, except that a Dendrite® Imaging System was employed to visualize the surgical field both in white light and NUVL. In all patients, all nerves fluoresced brightly throughout their course in the surgical field. Such visualization was crucial during resection of lymph nodes close to nerves. No peri-operative complications occurred and no evidence of neurological injury was evident at one-month follow-up.
CLINICAL DISCUSSION: The Dendrite® Imaging System employs a NUVL light source and filter system to detect fluorescent signals emitted by neural tissue. These signals then pass through a filter system within the camera head, are captured by a chip, and are transmitted to a dedicated software platform for real-time analysis, processing, and relay to a display screen, allowing the surgical team to observe neural structures with clarity.
CONCLUSION: In three breast cancer patients undergoing ALND, nerve autofluorescence under NUVL aided in visualizing and preventing injury to all nerves within the surgical field.

Keywords:  Axillary lymph node dissection; Breast cancer; Dendrite® imaging system; Fluorescence imaging; Iatrogenic nerve injury; Nerve-sparing surgery

DOI:  https://doi.org/10.1016/j.ijscr.2024.110723
Front Mol Biosci. 2024 ;11 1451611

MMP9: Link between neuropathy and colorectal cancer?

Cynthia Rosa Regalado, Mihály Balogh.

  As chemotherapy is still a cornerstone of colorectal cancer (CRC) treatment, chemotherapy-induced peripheral neuropathy (CIPN) presents significant clinical challenges, affecting millions worldwide. A subset of colon cancer patients (approximately 30%) develop chronic CIPN, with detrimental, untreatable neuropathic pain symptoms. The risk factors of such intractable chronic CIPN are unknown. However, there is growing literature data investigating the intriguing interplay of neurons and cancer (cancer neuroscience). Recent data shows that this interplay might have a key role in the development and severity of CIPN. Given its vast (patho)physiological roles in both colon cancer and neuropathy, MMP9 seems to be a key factor that might drive the development of neuronal damage in colon cancer patients. This review investigates the role of matrix metalloproteinase 9 (MMP9) in linking CRC to neuropathy, aiming to uncover shared mechanisms that could offer new therapeutic targets. By synthesizing insights from a broad range of studies published over the last 20 years, we explore MMP9's involvement in CRC progression, its role in CIPN, and the interconnected pathways influencing both conditions. These studies reveal MMP9 as a pivotal mediator in ECM remodeling, inflammation, and signal transduction pathways, emphasizing its modulation by macrophages. These shared mechanisms of colon cancer and CIPN pathophysiology suggest MMP9's potential contribution to neuropathic conditions in CRC patients, positioning it as a critical factor in disease progression and a promising therapeutic target. Future research should focus on longitudinal studies to assess MMP9's impact on neuropathy outcomes in CRC patients, exploring MMP9 inhibitors, and developing targeted interventions to mitigate the detrimental symptoms of CIPN. MMP9 also seems to be a feasible driving factor in the development of chronic CIPN in colon cancer patients.

Keywords:  CIPN; MMP9; cancer neuroscience; colon cancer; colorectal cancer; matrix metalloproteinase 9; neuropathy

DOI:  https://doi.org/10.3389/fmolb.2024.1451611
Neurogastroenterol Motil. 2024 Dec 09. e14976

Chemotherapy-Induced Neuropathy Affecting the Gastrointestinal Tract.

Gema Vera, Kulmira Nurgali, Raquel Abalo.

   BACKGROUND: Cancer is a major global cause of morbidity and mortality. Survivorship is increasing, bringing new challenges. Cancer treatment, including chemotherapeutic drugs, immunotherapy, and radiotherapy, can have severe and impactful gastrointestinal side effects occurring shortly after treatment (acute toxicity) or persisting for years after treatment ends (late/chronic toxicity).
PURPOSE: The aim of this article is to review the neurotoxic effects of chemotherapy on the enteric nervous system (ENS) and the gut extrinsic innervation. These effects could contribute to the development of long-term gastrointestinal dysfunctions. Research, primarily conducted in animal models, indicates that antitumoral drugs can lead to chemotherapy-induced enteric neuropathy (CIEN). Studies, mainly performed in the myenteric plexus, show that CIEN is characterized by a reduced density of nerve cells and fibers, as well as an imbalanced representation of neuronal subpopulations or their markers, with enteric glial cells also affected. These alterations underlie changes in neuronal activity and gastrointestinal motor function. Although research on the submucosal plexus remains limited, evidence suggests that CIEN affects the entire ENS. Furthermore, scarce studies show that CIEN also occurs in humans. Moreover, emerging experimental data on chemotherapy-induced alterations in visceral sensitivity suggest that the extrinsic innervation of the gut is also affected, but this has received little attention thus far. Nevertheless, this could contribute to the development of chemotherapy-induced brain-gut axis (BGA) disorders in the long term. Cancer chemotherapy (and probably also immunotherapy and radiotherapy) seems to cause neuropathic effects on the intrinsic and extrinsic innervation of the gastrointestinal tract, with an important impact on gastrointestinal and BGA functions. This is a relatively neglected area deserving further investigation.

Keywords:  brain–gut axis; cancer; chemotherapy; enteric; gastrointestinal; neurotoxicity

DOI:  https://doi.org/10.1111/nmo.14976
Biochim Biophys Acta Rev Cancer. 2024 Dec 06. pii: S0304-419X(24)00166-5. [Epub ahead of print] 189235

Organoids in lung cancer brain metastasis: Foundational research, clinical translation, and prospective outlooks.

Mei Zheng, Jialin Qu, Dongxi Xiang, Ligang Xing.

  Brain metastasis stands as a leading contributor to mortality in lung cancer patients, yet the intricate mechanism underlying this phenomenon remains elusive. This underscores the need for robust preclinical models and effective treatment strategies. Emerging as viable in vitro models that closely replicate actual tumors, three-dimensional culture systems, particularly organoids derived from non-malignant cells or cancer organoids, have emerged as promising avenues. This review delves into the forefronts of fundamental research and clinical applications focused on lung cancer brain metastasis-derived organoids, highlighting current challenges and delineating prospects. These studies offer tremendous potential for clinical application despite being in nascent status.

Keywords:  Lung cancer brain metastasis (LCBM); Organoids; Preclinical models

DOI:  https://doi.org/10.1016/j.bbcan.2024.189235
Cureus. 2024 Nov;16(11): e73169

Extraneural Soft Tissue Perineurioma: A Report of a Rare Case of Peripheral Nerve Sheath Tumor.

Ramki Arunachalam Ganesh, Karthikeyan Selvaraj, Srinivasan Chandran, Jesu Pencilin Yesuvadiyan.

  Extraneural perineuriomas are rare, benign soft tissue tumors arising from perineurial cells, which form the protective lining of peripheral nerves. These tumors are infrequently encountered in the foot, posing diagnostic challenges due to their rarity and non-specific clinical presentation. Here, we describe the case of a 45-year-old woman, who had a swelling over the right foot dorsum for four years for which an excision biopsy was done. Her histopathological variant and immunohistochemistry were consistent with extraneural perineurioma. This article aims to present a comprehensive review of extraneural perineuriomas, focusing on a case study involving the foot, and to discuss the clinical and histopathological characteristics, differential diagnosis, treatment options, and prognosis of this uncommon entity.

Keywords:  benign peripheral nerve sheath tumor; benign tumor; extraneural perineurioma; perineurioma; soft tissue tumor

DOI:  https://doi.org/10.7759/cureus.73169
Int J Surg Pathol. 2024 Dec 12. 10668969241300504

Combined Ganglioneuroma-Schwannoma of the Retroperitoneum: An Exceedingly Rare Hybrid Nerve Sheath-Ganglioneural Tumor.

Ming Liang Oon, Hui Min Tan, Sarah S Tang, Sujith Wijerathne, Ning Qi Pang, Iyer Shridhar Ganpathi, Kee Yuan Ngiam, Rajeev Parameswaran, Min En Nga.

  Combined ganglioneuroma-schwannoma is an exceedingly rare tumor that has only been described in isolated case reports. We document a 64-year-old man with an incidentally discovered combined ganglioneuroma-schwannoma of the retroperitoneum that was intimately associated with sympathetic ganglia. We highlight the morphological and immunohistochemical findings of this rare tumor, and show evidence of its origin from sympathetic ganglia.

Keywords:  ganglioneuroma; hybrid; nerve sheath tumor; schwannoma

DOI:  https://doi.org/10.1177/10668969241300504