bims-netuvo 2023-08-20 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023–08–20
eight papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Research progress of neural invasion in pancreatic cancer.
Benign peripheral nerve sheath tumors: an interdisciplinary diagnostic and therapeutic challenge.
Impact of clinical and histopathological characteristics on the disease-free survival of stage I-II acral melanoma patients.
Inverse correlation between Alzheimer's disease and cancer from the perspective of hypoxia.
Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition.
Pancreatic schwannoma: a rare differential diagnosis for a pancreatic mass.
Exploring the Rules of Related Parameters in Transcutaneous Electrical Nerve Stimulation for Cancer Pain Based on Data Mining.
Mini-Review: Enteric glia of the tumor microenvironment: An affair of corruption.

Curr Cancer Drug Targets. 2023 Aug 17.

Research progress of neural invasion in pancreatic cancer.

Mengying Zhu, Feng Luo, Bin Xu, Jian Xu.

  Pancreatic cancer is one of the highly malignant gastrointestinal tumors in humans, and patients suffer from cancer pain in the process of cancer. Most patients suffer from severe pain in the later stages of the disease. The latest studies have shown that the main cause of pain in patients with pancreatic cancer is neuroinflammation caused by tumor cells invading nerves and triggering neuropathic pain on this basis, which is believed to be the result of nerve invasion. Peripheral nerve invasion (PNI), defined as the presence of cancer cells along the nerve or in the epineurial, perineural, and endoneurial spaces of the nerve sheath, is a special way for cancer to spread to distant sites. However, due to limited clinical materials, the research on the mechanism of pancreatic cancer nerve invasion has not been carried out in depth. In addition, perineural invasion is considered to be one of the underlying causes of recurrence and metastasis after pancreatectomy and an independent predictor of prognosis. This article systematically reviewed the neural invasion of pancreatic cancer through bioinformatics analysis, clinical manifestations and literature reviews.

Keywords:  Cancer microenvironment; Cancer pain; Molecular mechanism; PNI; Pancreatic cancer

DOI:  https://doi.org/10.2174/1568009623666230817105221
Neurosurg Rev. 2023 Aug 18. 46(1): 205

Benign peripheral nerve sheath tumors: an interdisciplinary diagnostic and therapeutic challenge.

Anne-Kathrin Uerschels, Nora F Dengler, Mehdi Chihi, Annika Lenkeit, Thiemo F Dinger, Ramazan Jabbarli, Ulrich Sure, Tim Hagenacker, Karsten H Wrede, Oliver Gembruch.

  A benign peripheral nerve sheath tumor (bPNST) is a rare lesion associated with peripheral nerval structures. Symptoms may be heterogeneous, complicating diagnosis finding. Additionally, management concepts of bPNST may vary. In some cases, initial misdiagnosis leads to mistreatment resulting in severe functional deficits and chronic pain syndromes. Therefore, we analyzed patients treated for bPNST in our specialized institution with a primary focus on prior misdiagnosis and possible mistreatment. Patients with bPNSTs (schwannomas, neurofibromas, hybrid nerve sheath tumors, and perineuriomas) treated at the Neurosurgical Department between January 1, 2015, and July 31, 2021, were included. Assessment of demographics, tumor entity, tumor location, symptoms, the interval between the onset of symptoms and surgery, involved medical specialties, and outpatients' treatment, with particular focus on initial misdiagnosis and inappropriate medical treatment, was performed. Eighty-five patients were included in the final analysis with schwannoma being the most prevalent histopathological diagnosis (schwannoma (75.3%, n=64), neurofibroma (12.9%, n=11), hybrid nerve sheath tumor (5.9%, n=5), and perineurioma (5.9%, n=5)). An incorrect primary diagnosis was detected in 44.7% (n=38), leading to suboptimal or insufficient treatment in these cases. Of those, 28.9% (n=11/38) were treated suboptimal, while 18.5% (n=7/38) underwent unnecessary invasive diagnostics. Inappropriate surgery based on prior misdiagnosis, which led to severe neurological deficits in all these cases, was reported in 26.3% (n=10/38). For the first time, our data shows the quantity and impact of incorrect initial diagnosis in bPNST causing a delay in causative treatment or resulting in unnecessary or potentially harmful treatment.

Keywords:  Benign peripheral nerve sheath tumors; Diagnostics; Misdiagnosis; Mistreatment

DOI:  https://doi.org/10.1007/s10143-023-02107-z
Int J Dermatol. 2023 Aug 18.

Impact of clinical and histopathological characteristics on the disease-free survival of stage I-II acral melanoma patients.

Raquel Borges de Barros Primo, Aretha Brito Nobre, Bruna Nathália Santos, Luiz Fernando Nunes, Ricardo Fernandes Santos, Patricia Abrão Possik, Sara Santos Bernardes.

BACKGROUND: Acral melanoma is rare and associated with a worse prognosis compared to cutaneous melanoma in other locations. Despite this, few studies have focused on the prognosis of acral melanoma, particularly in patients with initial clinical stage. The aim of this study was to assess the impact of clinical and histopathological characteristics on the disease-free survival (DFS) of stage I-II patients.
METHODS: We analyzed 154 stage I-II acral melanoma cases, all of whom underwent a review of the histopathological and clinical parameters. Patients were divided into groups based on the presence or absence of disease recurrence within 5 years. We used Cox proportional regression to analyze independent risk factors and computed DFS curves using the Kaplan-Meier method.
RESULTS: Within 5 years, 27.9% of patients experienced disease recurrence, with 90.4% occurring during the first 3 years. Univariate and multivariate analyses did not identify any clinical parameters with a significant influence on DFS. The DFS rate at 5 years was 72.7%. The median duration of disease recurrence after the initial diagnosis was 21 months. However, Breslow thickness, presence of ulceration, >3 mitosis/mm2 , presence of tumor-infiltrating lymphocytes (TIL), and perineural invasion were significantly associated with a decrease in time to first recurrence.
CONCLUSIONS: Despite the favorable prognosis of stage I-II acral melanoma compared with advance stage, clinical and histopathological characteristics can impact prognosis. In addition to Breslow thickness and ulceration, attention should be paid to mitotic rate, presence of TIL, and perineural invasion to optimize follow-up of acral melanoma patients diagnosed in the initial clinical stage.

DOI: https://doi.org/10.1111/ijd.16800
Neurobiol Aging. 2023 Jul 06. pii: S0197-4580(23)00136-7. [Epub ahead of print]131 59-73

Inverse correlation between Alzheimer's disease and cancer from the perspective of hypoxia.

Zhan Su, Guimei Zhang, Xiangting Li, Haining Zhang.

  Sporadic Alzheimer's disease and cancer remain epidemiologically inversely related, and exploring the reverse pathogenesis is important for our understanding of both. Cognitive dysfunctions in Alzheimer's disease (AD) might result from the depletion of adaptive reserves in the brain. Energy storage in the brain is limited and is dynamically regulated by neurovascular and neurometabolic coupling. The research on neurodegenerative diseases has been dominated by the neurocentric view that neuronal defects cause the diseases. However, the proposal of the 2-hit vascular hypothesis in AD led us to focus on alterations in the vasculature, especially hypoperfusion. Chronic hypoxia is a feature shared by AD and cancer. It is interesting how contradicting chronic hypoxia's effects on both cancer and AD are. In this article, we discuss the potential links between the 2 diseases' etiology, from comparable upstream circumstances to diametrically opposed downstream effects. We suggest opposing potential mechanisms, including upregulation and downregulation of hypoxia-inducible factor-1α, the Warburg and reverse-Warburg effects, lactate-mediated intracellular acidic and alkaline conditions, and VDAC1-mediated apoptosis and antiapoptosis, and search for regulators that may be identified as the crossroads between cancer and AD.

Keywords:  Alzheimer's disease; Cancer; Hypoxia-inducible factors; Metabolic alteration; Warburg effect

DOI:  https://doi.org/10.1016/j.neurobiolaging.2023.07.002
J Cancer Res Clin Oncol. 2023 Aug 12.

Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition.

Balbina García-Reyes, Ivan Kuzmanov, Reiner Schneider, Bianca Schneiker, Patrik Efferz, Jörg C Kalff, Sven Wehner.

   BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, characterized by the spreading of highly metastatic cancer cells, including invasion into surrounding nerves and perineural spaces. Nerves, in turn, can invade the tumor tissue and, through the secretion of neurotrophic factors, chemokines, and cytokines, contribute to PDAC progression. However, the contribution of the nerve-associated glial cells to PDAC progression is not well characterized.
METHODS: Two murine PDAC cell lines were cultured with the conditioned media (CM) of primary enteric glial cells or IMS32 Schwann cells (SCs). Different properties of PDAC cells, such as invasiveness, migratory capacity, and resistance to gemcitabine, were measured by RT-qPCR, microscopy, and MTT assays. Using a neuronal cell line, the observed effects were confirmed to be specific to the glial lineage.
RESULTS: Compared to the control medium, PDAC cells in the glial cell-conditioned medium showed increased invasiveness and migratory capacity. These cells showed reduced E-cadherin and increased N-cadherin and Vimentin levels, all markers of epithelial-mesenchymal transition (EMT). Primary enteric glial cell CM inhibited the proliferation of PDAC cells but preserved their viability, upregulated transcription factor Snail, and increased their resistance to gemcitabine. The conditioned medium generated from the IMS32 SCs produced comparable results.
CONCLUSION: Our data suggest that glial cells can increase the metastatic potential of PDAC cells by increasing their migratory capacity and inducing epithelial-to-mesenchymal transition, a re-programming that many solid tumors use to undergo metastasis. Glial cell-conditioned medium also increased the chemoresistance of PDAC cells. These findings may have implications for future therapeutic strategies, such as targeting glial cell-derived factor signaling in PDAC.

Keywords:  Cell culture models; Glial cells; PDAC; Pancreatic cancer; Schwann cells

DOI:  https://doi.org/10.1007/s00432-023-05133-y
BJR Case Rep. 2023 Aug;9(4): 20230029

Pancreatic schwannoma: a rare differential diagnosis for a pancreatic mass.

Dana AlNuaimi, Shareefa Abdulghaffar, Giuseppe Iuppa, Ahmad AlDuaij, Noor Badrawi, Numan Cem Balci.

Pancreatic schwannomas are rare benign tumors with low malignant potential and are often difficult to diagnose due to their non-specific presenting symptoms and overlapping radiological imaging characteristics. Cross-sectional imaging plays an important role in the initial diagnosis and in delineating the extent of the lesion. However, biopsy and histopathological examination remains the gold-standard for a definite diagnosis. The management of pancreatic schwannomas includes surgical resection often yielding excellent clinical outcomes with low recurrence rates. We present a case of a 33-year-old female patient with a history of a recurrent vague upper abdominal pain where CT of the upper abdomen showed a hypodense pancreatic mass. Robotic subtotal pancreatectomy was done with histopathology showing spindled Schwann cells indicative of a pancreatic schwannoma.

DOI: https://doi.org/10.1259/bjrcr.20230029
Pain Ther. 2023 Aug 14.

Exploring the Rules of Related Parameters in Transcutaneous Electrical Nerve Stimulation for Cancer Pain Based on Data Mining.

Quan-Yao Li, Wen-Xiao Yang, Li-Qiu Yao, Hong Chen, Zhen-Rui Li, Ya-Bin Gong, Jun Shi.

   INTRODUCTION: This study aims to investigate the regularity of related parameters in the treatment of cancer pain using transcutaneous electrical nerve stimulation (TENS).
METHODS: A comprehensive literature search was conducted in databases such as PubMed, Cochrane Library, Embase, Web of Science, OVID, CNKI, CBM, VIP, and WANNGFANG from inception up to December 2022. A database was established, and data mining techniques were applied to analyze the relevant TENS parameters.
RESULTS: A total of 27 articles were included, encompassing nine current frequencies, four retention times, four treatment frequencies, and two wave types. On the basis of the analysis of parameter association rules, the most closely related parameter combination for clinical TENS in the treatment of cancer pain was a current frequency of 2/100 Hz, a treatment frequency of once a day, a retention time of 30 min, and the dilatational wave. Moreover, the study involved 22 acupuncture points distributed along 13 meridians. According to the analysis of acupuncture point association rules, Hegu (LI04), Zusanli (ST36), and Sanyinjiao (SP06) were the most closely related acupuncture points and could be used in combination for clinical TENS in cancer pain treatment. Furthermore, cluster analysis was conducted on acupuncture points with a frequency ≥ 5, resulting in three categories: the first category included Sanyinjiao (SP06), Zusanli (ST36), Hegu (LI04), Jiaji point, and Neiguan (PC06); the second category included Ashi point; and the third category included Back shu point.
CONCLUSION: In the treatment of cancer pain using TENS, it is recommended to use a current frequency of 2/100 Hz, a treatment frequency of once a day, a retention time of 30 min, and the dilatational wave. The electrode positions were primarily selected from Ashi point, Back shu point, Sanyinjiao (SP06), Zusanli (ST36), Hegu (LI04), Jiaji point, and Neiguan (PC06) to achieve the best analgesic effect.

Keywords:  Cancer; Cancer pain; Data mining; Parameters; Transcutaneous electrical nerve stimulation

DOI:  https://doi.org/10.1007/s40122-023-00549-3
Neurosci Lett. 2023 Aug 10. pii: S0304-3940(23)00375-0. [Epub ahead of print] 137416

Mini-Review: Enteric glia of the tumor microenvironment: An affair of corruption.

Chloe L Mariant, Gregory Bacola, Laurianne Van Landeghem.

  The tumor microenvironment corresponds to a complex mixture of bioactive products released by local and recruited cells whose normal functions have been "corrupted" by cues originating from the tumor, mostly to favor cancer growth, dissemination and resistance to therapies. While the immune and the mesenchymal cellular components of the tumor microenvironment in colon cancers have been under intense scrutiny over the last two decades, the influence of the resident neural cells of the gut on colon carcinogenesis has only very recently begun to draw attention. The vast majority of the resident neural cells of the gastrointestinal tract belong to the enteric nervous system and correspond to enteric neurons and enteric glial cells, both of which have been understudied in the context of colon cancer development and progression. In this review, we especially discuss available evidence on enteric glia impact on colon carcinogenesis. To highlight "corrupted" functioning in enteric glial cells of the tumor microenvironment and its repercussion on tumorigenesis, we first review the main regulatory effects of enteric glial cells on the intestinal epithelium in homeostatic conditions and we next present current knowledge on enteric glia influence on colon tumorigenesis. We particularly examine how enteric glial cell heterogeneity and plasticity require further appreciation to better understand the distinct regulatory interactions enteric glial cell subtypes engage with the various cell types of the tumor, and to identify novel biological targets to block enteric glia pro-carcinogenic signaling.

Keywords:  Cancer stem cell; Colon cancer; Enteric glial cell; Intestinal stem cell; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.neulet.2023.137416