bims-netuvo 2025-02-09 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2025–02–09
eleven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Rethinking metastatic brain cancer as a CNS disease.
SLEEP, CIRCADIAN RHYTHMS, AND LUNG CANCER.
Revealing shared molecular drivers of brain metastases from distinct primary tumors.
Hijacking of the nervous system in cancer: mechanism and therapeutic targets.
Primary Malignant Peripheral Nerve Sheath Tumor of the Cauda Equina: A Case Report and Literature Review.
The diagnostic utility of SOX11 Immunohistochemical expression in malignant peripheral nerve sheath tumors and their potential mimickers.
Exploring the biological mechanism and clinical value of perineural invasion in pancreatic cancer.
Pregabalin Combined With Opioids for Managing Neuropathic Pain in Patients With Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Retroperitoneal malignant peripheral nerve sheath tumor treated with laparotomy approach: A case report.
Multiple cutaneous nerve sheath tumours with myxoid differentiation in farmed Russian sturgeons (Acipenser gueldenstaedtii, Brandt and Ratzeburg 1833).
A rare case of asymptomatic retroperitoneal and thigh femoral nerve schwannoma.

Lancet Oncol. 2025 Feb;pii: S1470-2045(24)00430-3. [Epub ahead of print]26(2): e111-e121

Rethinking metastatic brain cancer as a CNS disease.

Jawad Fares, Edgar Petrosyan, Crismita Dmello, Rimas V Lukas, Roger Stupp, Maciej S Lesniak.

Advances in molecular biology, genetics, and epigenetics have refined our understanding of metastatic brain cancer and underscored the need for better classification and targeted approaches. The heterogeneity of brain metastases highlights the differences from their primary source of origin and contributes to therapeutic resistance. Before colonising the brain, tumour cells acquire specialised proficiencies that enable them to capitalise on the unique microenvironment of the brain. The tumour cells further orchestrate key adaptations to adjust to the brain microenvironment by manipulating the blood-brain barrier, evading immune surveillance, rewiring metabolic profiles, and reprogramming astrocytes. These adaptations facilitate tumour survival, growth, and treatment resistance. Recognising metastatic brain cancer as a distinctive CNS disease, rather than an extension of the primary cancer, would support the development of rational approaches that target its molecular and genetic features and improve research funding in this area. Here, we delve into the distinct genetic and phenotypic characteristics of metastatic brain cancer, and reflect on how a change in the perception of this disease could accelerate the development of more effective therapies and drive continued progress in the field of neuro-oncology.

DOI: https://doi.org/10.1016/S1470-2045(24)00430-3
Semin Respir Crit Care Med. 2025 Feb 03.

SLEEP, CIRCADIAN RHYTHMS, AND LUNG CANCER.

Daniel Cooper, Isaac Lopez, Tetyana Kendzerska.

Lung cancer is the leading cause of cancer-related mortality worldwide, with the prevalence of the disease continually rising. Therefore, identifying disease-modifying risk factors is critical, with increasing recognition of the impact of sleep quality/sleep disorders. This narrative review summarizes the evidence on the role of five domains of sleep on lung cancer incidence and progression: (i) sleep quality/duration, (ii) sleep disordered breathing, (iii) circadian rhythm disturbances, (iv) sleep-related movement disorders and (v) personal, environmental and social factors that modulate each of these associations. Epidemiological evidence supports reduced sleep duration, increased sleep duration, poor sleep quality, insomnia, obstructive sleep apnea, evening chronotype, peripheral limb movements in sleep, and less robustly for night shift work and restless leg syndrome to be associated with increased risk of lung cancer development, with potential impacts on cancer survival outcomes. Proposed mechanisms underlying the biological plausibility of these epidemiological associations are also explored, with common theories relating to immune dysregulation, metabolic alterations, reductions in melatonin, sympathetic overactivation, increased reactive oxygen species, production of protumorigenic exosomes and inflammation. We also summarized potential treatments addressing impaired sleep quality/sleep disorders and their ability to attenuate the risk of lung cancer and cancer survival. While evidence on reversibility is inconsistent, there are trends toward positive outcomes. Future research should focus on clinical trials to confirm cause and effect relationships, large epidemiologic studies for incidence/prognosis, clarification on the relative efficacy of treatment modalities, and more in vivo animal models to establish the molecular mechanisms underlying these relationships.

DOI: https://doi.org/10.1055/a-2531-1059
Brain Res. 2025 Jan 31. pii: S0006-8993(25)00014-9. [Epub ahead of print] 149456

Revealing shared molecular drivers of brain metastases from distinct primary tumors.

Carlos Alberto de Carvalho Fraga, Leandro Tiburske, Gabriel Victor Lucena da Silva, Adriana Simizo, Mauro Cesar Cafundó Morais, Ana Kelly da Silva Fernandes Duarte, Henry David Mogollón García, Thiago Dominguez Crespo Hirata, Helder I Nakaya.

  Brain metastasis is the most common type of brain cancer, associated with significant neurological dysfunction and a poor prognosis. We investigated the transcriptome of 128,421 single-cells of 36 brain metastases, originating from a variety of primary tumors, including melanoma, breast, lung, ovarian, colorectal, and renal cancers. Our aim was to identify common molecular factors across these tumors, shedding light on key interactions that facilitate tumor establishment in the brain. We specifically focused on the dynamics of the blood-tumor barrier and its effects on endothelial cells, pericytes, and astrocytes. Our analysis decoded complex cell-cell communications, emphasizing the crucial role of astrocytes in the tumor microenvironment (TME). This provided insights into how these interactions impact the permeability of the blood-tumor barrier and contribute to the development of brain metastases. We identified the VEGFA, SEMA3, and SPP1 pathways as key regulators in brain metastasis, affecting vascular permeability and cellular dynamics. Spatial transcriptome analysis confirmed our findings and linked these pathways to TME enrichment. The pronounced expression of VEGFA by cancer cells suggests a significant activation of angiogenic pathways, influencing vascular responses and the intricate architecture of brain tissue. The interplay of these signaling pathways underlines the complexity of molecular interactions that define the microenvironment of brain metastases.

Keywords:  Brain metastasis; Human metastasis; Metastatic niche; Metastatic program; Metastatic tumor cells; Metastatic tumors; Single cell; Spatial profiling

DOI:  https://doi.org/10.1016/j.brainres.2025.149456
Mol Cancer. 2025 Feb 06. 24(1): 44

Hijacking of the nervous system in cancer: mechanism and therapeutic targets.

Yu Zhang, Qili Liao, Xuyang Wen, Jiayan Fan, Tifei Yuan, Xuemei Tong, Renbing Jia, Peiwei Chai, Xianqun Fan.

  The activity of neurons in the vicinity of tumors is linked to a spectrum of cellular mechanisms, including the facilitation of tumor cell proliferation, synapse formation, angiogenesis, and macrophage polarization. This review consolidates the current understanding of neuro-oncological regulation, underscoring the nuanced interplay between neurological and oncological processes (termed as Cancer-Neuroscience). First, we elucidated how the nervous system accelerates tumor growth, metastasis, and the tumor microenvironment both directly and indirectly through the action of signaling molecules. Importantly, neural activity is also implicated in modulating the efficacy of therapeutic interventions, including immunotherapy. On the contrary, the nervous system potentially has a suppressive effect on tumorigenesis, further underscoring a dual-edged role of neurons in cancer progression. Consequently, targeting specific signaling molecules within neuro-oncological regulatory pathways could potentially suppress tumor development. Future research is poised to explore the intricate mechanisms governing neuro-tumor interactions more deeply, while concurrently refining treatment strategies for tumors by targeting the crosstalk between cancer and neurons.

Keywords:  Cancer; Nervous system; Neurotransmitters; Neurotrophic factors; Therapeutic implications; Tumor microenvironment

DOI:  https://doi.org/10.1186/s12943-025-02246-5
Cureus. 2025 Jan;17(1): e77096

Primary Malignant Peripheral Nerve Sheath Tumor of the Cauda Equina: A Case Report and Literature Review.

Hoai Tp Dinh, Vu H Nguyen, Dung Tm Nguyen, Minh T Nguyen, Yoko Kato.

  Primary malignant peripheral nerve sheath tumors (MPNSTs) arising within the cauda equina are exceptionally rare, with only 24 cases documented in English-language literature. Due to its infrequency and aggressive behavior, no standardized treatment approach has been established. This report presents a case of primary MPNST of the cauda equina, accompanied by a comprehensive literature review, aiming to elucidate the management strategies and prognosis of this uncommon yet highly malignant tumor. A 62-year-old male was diagnosed with primary intradural MPNST and underwent gross total resection (GTR) with laminectomy along with adjunctive high-energy radiotherapy. Concurrently, we analyze existing literature concerning intradural MPNSTs. Surgical resection remains the mainstay of MPNST management, although its efficacy is limited by high recurrence rates. Despite aggressive treatment modalities, including radiotherapy and chemotherapy, primary intradural MPNSTs exhibit a propensity for leptomeningeal and systemic dissemination, contributing to a dismal overall prognosis. Notably, outcomes appear to be graver compared to MPNSTs in other anatomical locations. Primary intradural MPNSTs represent a rare and formidable clinical challenge characterized by poor prognostic outcomes. While surgical excision supplemented by adjuvant radiotherapy may offer some benefit, the need for effective targeted therapies associated with neurofibromatosis type 1 (NF1) needs to be studied more to delineate optimal treatment strategies and improve patient outcomes.

Keywords:  cauda equina; gross total resection; malignant tumor; peripheral nerve sheath tumor; radiotherapy

DOI:  https://doi.org/10.7759/cureus.77096
Ann Diagn Pathol. 2025 Jan 29. pii: S1092-9134(25)00012-7. [Epub ahead of print]75 152447

The diagnostic utility of SOX11 Immunohistochemical expression in malignant peripheral nerve sheath tumors and their potential mimickers.

Elif Tasar Kapakli, Melike Pekmezci, Kubra Katipoglu, Figen Soylemezoglu, Gokhan Gedikoglu, Tarık Tihan, Kemal Kosemehmetoglu.

  Malignant peripheral nerve sheath tumor (MPNST) comprises 5-10 % of all soft tissue sarcomas, and their diagnosis may be challenging given the absence of robust immunohistochemical and molecular signatures. SOX11 expression has previously been shown to be present in a small subset of MPNST. In the present study, we evaluated a group of MPNST for SOX11 expression by immunohistochemistry. We similarly assessed a group of benign and malignant spindle cell tumors that are in the differential diagnosis of MPNST, to more expansively establish the specificity of the antibody. In total, 59 MPNSTs, 27 synovial sarcomas, 19 leiomyosarcomas, 19 rhabdomyosarcomas, 19 solitary fibrous tumors, 4 clear cell sarcomas of soft tissue, 19 malignant melanomas, 22 schwannomas (11 classical, 11 cellular), 9 neurofibromas (4 plexiform, 2 atypical, and 3 classical) and 9 nodular fasciitis were included. SOX11 was strongly positive in 41 of 59 MPNSTs (67 %), 16 of 27 synovial sarcomas (59 %), 11 of 19 rhabdomyosarcomas (58 %), 1 of 4 clear cell sarcomas (25 %), and 5 of 9 nodular fasciitis (56 %). In contrast, neurofibromas(n=11)), schwannomas (n=22), leiomyosarcomas (n=22), and solitary fibrous tumors (n=19) were either negative or showed only weak and focal expression for SOX11. The sensitivity and specificity of strong SOX11 expression in differentiating MPNST from its mimickers were 70 % and 73 %, respectively. In conclusion, the diagnostic utility of SOX11 expression for MPNST is limited, but the absence of significant SOX11 expression in benign/atypical nerve sheath tumors is interesting and deserves further investigation.

Keywords:  Mesenchymal tumors; Nerve sheath tumors; SOX11 8; Sarcoma

DOI:  https://doi.org/10.1016/j.anndiagpath.2025.152447
Cancer Lett. 2025 Jan 31. pii: S0304-3835(25)00079-5. [Epub ahead of print]613 217515

Exploring the biological mechanism and clinical value of perineural invasion in pancreatic cancer.

Hao Yuan, Yufeng Zhang, Fengyuan Liu, Yang Wu, Xumin Huang, Xinjian Liu, Luyang Jiang, Bin Xiao, Yi Zhu, Qun Chen, Pengfei Wu, Kuirong Jiang.

  Pancreatic cancer (PC) is an extremely aggressive malignancy, with a 5-year survival rate of only 13 %. Perineural invasion (PNI) is a hallmark pathological feature of PC and is observed in almost all cases. Accordingly, PC ranks highly among solid tumors in terms of PNI incidence. The interaction between PC and the nervous system plays a pivotal role in tumor growth and metastasis. In PC, PNI is a key driver of local tumor progression, distant metastasis, and poor prognosis. Clarification of tumor-nerve crosstalk and the underlying molecular mechanisms is needed to facilitate the development of new therapeutic strategies to slow PC progression and alleviate PNI-associated symptoms. In this review, we present a comprehensive overview of the manifestations and characteristics of PNI in PC, summarize the molecular networks that regulate PNI, examine the relationship between PNI and the tumor microenvironment, and discuss the current research challenges and future directions in this critical area.

Keywords:  Cancer innervation; Clinical value; Molecular mechanism; Pancreatic cancer; Perineural invasion

DOI:  https://doi.org/10.1016/j.canlet.2025.217515
Pain Physician. 2025 Jan;28(1): 1-10

Pregabalin Combined With Opioids for Managing Neuropathic Pain in Patients With Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Chuanbing Wen, Maoying Wang, Maotong Liu, Chenyu Zhu, Jinlong Zhao, Qing Jiang, RuRong Wang, Jun Li, Li Song.

BACKGROUND: Cancer-related neuropathic pain significantly affects patients' quality of life. Despite existing treatments, pain control remains inadequate for many of these patients. There is a lack of strong evidence for the efficacy of the combination of pregabalin, which is often used to treat neuropathic pain, and opioids for treating cancer-related neuropathic pain.
OBJECTIVE: This study aimed to evaluate the analgesic effects and safety of pregabalin combined with opioids for managing cancer-related neuropathic pain through high-quality evidence analysis.
STUDY DESIGN: A systematic review and meta-analysis of pregabalin combined with opioids for cancer-related neuropathic pain.
METHODS: We systematically searched the PubMed, Web of Science, Embase, Cochrane Library and Cochrane Central Register of Controlled Trials databases from their inception through October 5, 2023. Two reviewers independently selected studies and extracted articles that met the inclusion and exclusion criteria. Quality assessments of the included studies were performed using the modified Cochrane Collaboration tool; data analysis was performed using RevMan 5.4 (The Nordic Cochrane Centre for The Cochrane Collaboration).
RESULTS: A total of 8 studies were included in our qualitative synthesis, and 6 studies were included in the meta-analysis (6 studies with 757 patients, including 342 in the experimental group and 415 in the control group). The results showed a significant difference between the pregabalin combined with opioids group and the opioids alone group in terms of Numeric Rating Scale (NRS-11) pain scores (weighted mean difference [WMD] = -1.00; 95% CI, -1.29 to -0.70; P < 0.001). However, no significant difference in the NRS-11 score was observed between the pregabalin combined with opioids group and active comparator combined with opioids group (WMD = -0.47; 95% CI, -1.05 to 0.11; P = 0.11). There was a significant difference between the pregabalin combined with opioids group and the active comparator combined with opioids group in terms of extra morphine milligram equivalents (relative risk [RR] = 0.37; 95% CI, 0.20 to 0.70; P = 0.002). No significant difference was observed in quality of life (WMD = -2.01; 95% CI, -5.29 to 1.27; P = 0.23). In general, the frequency of adverse events in the pregabalin combined with opioids group was greater than that in the opioids alone group, but the frequency of adverse events between the pregabalin combined with opioids group and the active comparator combined with opioids group was unclear.
LIMITATIONS: The limited number of articles and sample size are the limitations of this meta-analysis.
CONCLUSIONS: Pregabalin combined with opioids reduces cancer-related neuropathic pain but increases dizziness, somnolence, and peripheral edema, thus supporting its use in the clinic for treating cancer-related neuropathic pain. However, further high-quality randomized controlled trials are needed to confirm these findings.

Keywords: cancer pain; meta-analysis; systematic review ; Pregabalin
Int J Surg Case Rep. 2025 Feb 01. pii: S2210-2612(25)00184-1. [Epub ahead of print]128 110998

Retroperitoneal malignant peripheral nerve sheath tumor treated with laparotomy approach: A case report.

Intan Andaru, Wahjoe Djatisoesanto, Karinda Triharyu Caesari Putri.

   INTRODUCTION: Malignant peripheral nerve sheath tumors (MPNST) are sporadic neoplasms that present significant diagnostic challenges, particularly in retroperitoneal locations. While these aggressive tumors most commonly occur in the head, neck, and upper extremities, retroperitoneal cases represent a mere 1 % of all instances. This case study examines a specific instance of retroperitoneal MPNST diagnosed and treated through laparotomy, with the primary objective of enhancing medical professionals' understanding of this uncommon tumor's diagnostic complexities, treatment approaches, and potential prognostic implications. By highlighting such a rare clinical scenario, the research seeks to raise awareness among clinicians about the nuanced considerations required when encountering these challenging and infrequent malignancies in unusual anatomical regions.
CASE PRESENTATION: During a medical investigation of abdominal pain in a 44-year-old female patient, advanced imaging revealed a complex mass located in the left adrenal gland. Computed tomography scans demonstrated significant anatomical involvement, with the tumor compressing adjacent structures, including the pancreas and spleen superiorly, the left kidney and renal vasculature inferiorly, and positioned adjacent to the abdominal aorta. Surgical intervention was undertaken with the objective of complete tumor removal, successfully achieving unambiguous surgical margins. Subsequent immunohistochemical analysis confirmed the diagnosis of an MPNST, providing critical insights into the nature of the patient's complex medical condition.
DISCUSSION: MPNST represents a complex and challenging neoplasm characterized by its highly invasive and rapidly progressing nature, originating from neural tissue. The diagnostic process for MPNST is intricate, primarily due to the absence of definitive histological criteria and a distinctive immune profile. Critical diagnostic challenges emerge from the significant morphological similarities between MPNST and other tumors, such as fibrosarcomas and leiomyosarcomas. In this specific case, pathological anatomy initially suggested a liposarcoma lesion; however, immunohistochemistry testing revealed a negative Desmin result, effectively eliminating the liposarcoma diagnosis and underscoring the nuanced complexity of accurate tumor classification.
CONCLUSION: This case report highlights the diagnostic difficulty in identifying divergent differentiation in sarcomas, using MPNST and liposarcoma as examples.

Keywords:  Laparotomy; MPNST; Malignant; Retroperitoneal tumor

DOI:  https://doi.org/10.1016/j.ijscr.2025.110998
Vet Res Commun. 2025 Feb 01. 49(2): 95

Multiple cutaneous nerve sheath tumours with myxoid differentiation in farmed Russian sturgeons (Acipenser gueldenstaedtii, Brandt and Ratzeburg 1833).

Luciana Mandrioli, Ginevra Brocca, Samuele Zamparo, Massimo Orioles, Maria Morini, Luana Cortinovis, Eleonora Fiocchi, Maral Anjomanibenisi, Anna Toffan, Tobia Pretto, Ranieri Verin.

  Sturgeon species are well-suited for aquaculture because of their favourable characteristics, including robustness, suitability for farming in facilities unsuitable for other fish species, and adaptability to diverse farming conditions. The Russian sturgeon (Acipenser gueldenstaedtii, Brandt and Ratzeburg 1833) is one of the most prominent farmed species; however, like other aquaculture species, it is susceptible to significant losses from bacterial and viral diseases. Beyond infectious causes, there are few reports documenting conditions that produce cutaneous masses in Russian sturgeons. This study presents a multidisciplinary investigation of six farmed Russian sturgeons exhibiting discrete, multiple cutaneous masses. Bacteriological analysis of tissue samples revealed the presence of Morganella morganii and Aeromonas veronii biovar sobria, identified as opportunistic bacteria. Virological assays targeting the principal viruses affecting sturgeon, Acipenser iridovirus and Acipenser herpesvirus, yielded negative results. Ultrastructural analysis with direct negative staining revealed no evidence of biological agents. Histologically, the dermal masses were well-demarcated, expansile, and moderately cellular, consisting of spindle-to-stellate neoplastic cells that were multifocally periodic acid-Schiff-positive and embedded in abundant alcianophilic ground substance. Immunohistochemistry with the S-100 antibody confirmed cytoplasmic staining of the neoplastic cells. A final diagnosis of cutaneous nerve sheath tumour with myxoid differentiation was made, replicating findings from a similar tumour in rainbow trout. To the best of our knowledge, this represents the first description of multiple cutaneous nerve sheath tumours in sturgeon species. The potential factors contributing to the development of this neoplastic condition are discussed.

Keywords:   Acipenser gueldenstaedtii ; Cutaneous tumours; Fish neoplasms; Russian sturgeon

DOI:  https://doi.org/10.1007/s11259-025-10662-7
Radiol Case Rep. 2025 Apr;20(4): 1915-1919

A rare case of asymptomatic retroperitoneal and thigh femoral nerve schwannoma.

Jurjana Novoselac, Luka Simetić, Damir Jemendžić, Darija Mužinić, Ivana Jurca.

  We present a rare case of an asymptomatic extensive tumor in the retroperitoneum and thigh, which has not been published in the scientific literature so far. During the preventive examination, in an otherwise healthy 29-years old man, a tumor mass in the lower left abdominal quadrant was observed on ultrasound. A computed tomography scan and magnetic resonance imaging revealed a large, lobulated, multiseptated retroperitoneal mass stretching from the level of the lower left kidney pole to the distal third of the left thigh. Positron emission tomography/ computed tomography showed weak metabolically active mass with low probability of malignancy, and radiological differential diagnosis included lymphangioma, less likely lymphoma and as least likely sarcoma. Due to the assumed liquid content of the tumor, no preoperative biopsy was performed. A demanding and long-lasting operation was performed on Department of abdominal surgery at Clinical Hospital Merkur. The tumor was removed completely along with most part of the femoral nerve. Pathohistological analysis showed a benign tumor of the nerve sheath- schwannoma. A novel aspect in the presentation of this clinical entity is the extensiveness of the neoplasm to multiple regions without symptoms. According to the available literature, only 2 similar case reports are described, which were symptomatic.

Keywords:  Femoral Nerve; Neoplasms; Neurilemmoma (Schwannoma); Preventive health services; Retroperitoneal Space; Upper Leg

DOI:  https://doi.org/10.1016/j.radcr.2025.01.024