bims-netuvo 2024-03-17 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2024–03–17
sixteen papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Multiple cancer cell types release LIF and Gal3 to hijack neural signals.
Clinical significance of location of perineural cancer invasion detected on prostate needle core biopsy.
Cholangiocarcinoma Malignant Traits Are Promoted by Schwann Cells through TGFβ Signaling in a Model of Perineural Invasion.
Discrimination of benign, atypical, and malignant peripheral nerve sheath tumors in neurofibromatosis type 1 using diffusion-weighted MRI.
Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning.
Video-assisted thoracic surgery for an endobronchial ancient schwannoma obstructing the left main bronchus.
The NF1+/- Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant Transformation.
Laser Interstitial Thermal Therapy as a Treatment Option for Malignant Peripheral Nerve Sheath Tumor Metastases to the Brain: A Case Report.
Inhibition of GABAergic neurons in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice.
p53 modulates kinase inhibitor resistance and lineage plasticity in NF1-related MPNSTs.
Retrograde tracing of breast cancer-associated sensory neurons.
Ligand-gated ion channels as potential biomarkers for ADT-mediated cognitive decline in prostate cancer patients.
[Surgically Resected Cases of Mediastinal Ganglioneuroma Detected in Adults].
High-frequency ultrasound imaging findings in the diagnosis of segmental schwannomatosis of the ulnar nerve: case report and literature review.
DACIT: Device for Axon - Cancer cell Interaction Testing in 2D and 3D.
Characteristics of Early Pancreatic Cancer: Comparison between Stage 1A and Stage 1B Pancreatic Cancer in Multicenter Clinical Data Warehouse Study.

Cell Res. 2024 Mar 11.

Multiple cancer cell types release LIF and Gal3 to hijack neural signals.

Qun Xu, Ying Cao, Fanni Kong, Jiaqi Liu, Xin Chen, Yifei Zhao, Chin-Hui Lai, Xin Zhou, Hao Hu, Wei Fu, Jian Chen, Jing Yang.

Neural signals can significantly influence cancer prognosis. However, how cancer cells may proactively modulate the nervous system to benefit their own survival is incompletely understood. In this study, we report an overlapping pattern of brain responses, including that in the paraventricular nucleus of the hypothalamus, in multiple mouse models of peripheral cancers. A multi-omic screening then identifies leukemia inhibitory factor (LIF) and galectin-3 (Gal3) as the key cytokines released by these cancer cell types to trigger brain activation. Importantly, increased plasma levels of these two cytokines are observed in patients with different cancers. We further demonstrate that pharmacologic or genetic blockage of cancer cell-derived LIF or Gal3 signaling abolishes the brain responses and strongly inhibits tumor growth. In addition, ablation of peripheral sympathetic actions can similarly restore antitumor immunity. These results have elucidated a novel, shared mechanism of multiple cancer cell types hijacking the nervous system to promote tumor progression.

DOI: https://doi.org/10.1038/s41422-024-00946-z
Virchows Arch. 2024 Mar 15.

Clinical significance of location of perineural cancer invasion detected on prostate needle core biopsy.

Benjamin G Gertsen, Yuki Teramoto, Ying Wang, Toyonori Tsuzuki, Hiroshi Miyamoto.

  The clinical impact of site-specific perineural invasion (PNI) in prostate cancer remains poorly understood. We compared radical prostatectomy findings and oncologic outcomes in 434 patients with single-site PNI on systematic sextant biopsy. PNI was present in the right apex (n = 62; 14%), right mid (n = 70; 16%), right base (n = 89; 21%), left apex (n = 64; 15%), left mid (n = 58; 13%), and left base (n = 91; 21%). There were no significant differences in biopsy or prostatectomy findings, when comparing apex vs. mid vs. base PNI. Univariate analysis revealed that apex-localized PNI was associated with a significantly higher risk of progression, compared with base (P = 0.037) or mid/base (P = 0.024) PNI. Multivariable analysis showed that apex-localized PNI was an independent risk factor for progression (hazard ratio 2.049, P = 0.002). Among biopsies demonstrating PNI at one sextant site, apex-localized PNI is independently associated with poorer prognosis, though not worse histopathologic features on prostatectomy, compared with mid or base PNI.

Keywords:  Perineural invasion; Prognosis; Prostate biopsy; Prostate cancer; Radical prostatectomy

DOI:  https://doi.org/10.1007/s00428-024-03779-8
Cells. 2024 Feb 20. pii: 366. [Epub ahead of print]13(5):

Cholangiocarcinoma Malignant Traits Are Promoted by Schwann Cells through TGFβ Signaling in a Model of Perineural Invasion.

Valerio de Franchis, Simonetta Petrungaro, Elisa Pizzichini, Serena Camerini, Marialuisa Casella, Francesca Somma, Enrico Mandolini, Guido Carpino, Diletta Overi, Vincenzo Cardinale, Antonio Facchiano, Antonio Filippini, Eugenio Gaudio, Cinzia Fabrizi, Claudia Giampietri.

  The term cholangiocarcinoma (CCA) defines a class of epithelial malignancies originating from bile ducts. Although it has been demonstrated that CCA patients with perineural invasion (PNI) have a worse prognosis, the biological features of this phenomenon are yet unclear. Our data show that in human intrahepatic CCA specimens with documented PNI, nerve-infiltrating CCA cells display positivity of the epithelial marker cytokeratin 7, lower with respect to the rest of the tumor mass. In an in vitro 3D model, CCA cells move towards a peripheral nerve explant allowing contact with Schwann cells (SCs) emerging from the nerve. Here, we show that SCs produce soluble factors that favor the migration, invasion, survival and proliferation of CCA cells in vitro. This effect is accompanied by a cadherin switch, suggestive of an epithelial-mesenchymal transition. The influence of SCs in promoting the ability of CCA cells to migrate and invade the extracellular matrix is hampered by a specific TGFβ receptor 1 (TGFBR1) antagonist. Differential proteomic data indicate that the exposure of CCA cells to SC secreted factors induces the upregulation of key oncogenes and the concomitant downregulation of some tumor suppressors. Taken together, these data concur in identifying SCs as possible promoters of a more aggressive CCA phenotype, ascribing a central role to TGFβ signaling in regulating this process.

Keywords:  EMT; Schwann cells; TGFβ; bile duct cancer

DOI:  https://doi.org/10.3390/cells13050366
Neurooncol Adv. 2024 Jan-Dec;6(1):6(1): vdae021

Discrimination of benign, atypical, and malignant peripheral nerve sheath tumors in neurofibromatosis type 1 using diffusion-weighted MRI.

Inka Ristow, Michael G Kaul, Maria Stark, Antonia Zapf, Christoph Riedel, Alexander Lenz, Victor F Mautner, Said Farschtschi, Ivayla Apostolova, Gerhard Adam, Peter Bannas, Johannes Salamon, Lennart Well.

   Background: Neurofibromatosis type 1 (NF1) is associated with the development of benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumors. Recently described atypical neurofibromas (ANF) are considered pre-malignant precursor lesions to MPNSTs. Previous studies indicate that diffusion-weighted magnetic resonance imaging (DW-MRI) can reliably discriminate MPNSTs from BPNSTs. We therefore investigated the diagnostic accuracy of DW-MRI for the discrimination of benign, atypical, and malignant peripheral nerve sheath tumors.
Methods: In this prospective explorative single-center phase II diagnostic study, 44 NF1 patients (23 male; 30.1 ± 11.8 years) underwent DW-MRI (b-values 0-800 s/mm²) at 3T. Two radiologists independently assessed mean and minimum apparent diffusion coefficients (ADCmean/min) in areas of largest tumor diameters and ADCdark in areas of lowest signal intensity by manual contouring of the tumor margins of 60 BPNSTs, 13 ANFs, and 21 MPNSTs. Follow-up of ≥ 24 months (BPNSTs) or histopathological evaluation (ANFs + MPNSTs) served as diagnostic reference standard. Diagnostic ADC-based cut-off values for discrimination of the three tumor groups were chosen to yield the highest possible specificity while maintaining a clinically acceptable sensitivity.
Results: ADC values of pre-malignant ANFs clustered between BPNSTs and MPNSTs. Best BPNST vs. ANF + MPNST discrimination was obtained using ADCdark at a cut-off value of 1.6 × 10-3 mm2/s (85.3% sensitivity, 93.3% specificity), corresponding to an AUC of 94.3% (95% confidence interval: 85.2-98.0). Regarding BPNST + ANF vs. MPNST, best discrimination was obtained using an ADCdark cut-off value of 1.4 × 10-3 mm2/s (83.3% sensitivity, 94.5% specificity).
Conclusions: DW-MRI using ADCdark allows specific and noninvasive discrimination of benign, atypical, and malignant nerve sheath tumors in NF1.

Keywords:  DWI; MRI; apparent diffusion coefficient; malignant peripheral nerve sheath tumor; neurofibromatosis type 1

DOI:  https://doi.org/10.1093/noajnl/vdae021
World J Gastroenterol. 2024 Feb 14. 30(6): 542-555

Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning.

Hui-Ting Ge, Jian-Wu Chen, Li-Li Wang, Tian-Xiu Zou, Bin Zheng, Yuan-Fen Liu, Yun-Jing Xue, Wei-Wen Lin.

   BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.
AIM: To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.
METHODS: This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC).
RESULTS: In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05).
CONCLUSION: The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.

Keywords:  Gastric cancer; Lymphovascular invasion; Perineural invasion; Spectral computed tomography

DOI:  https://doi.org/10.3748/wjg.v30.i6.542
J Surg Case Rep. 2024 Mar;2024(3): rjae140

Video-assisted thoracic surgery for an endobronchial ancient schwannoma obstructing the left main bronchus.

Jiyeon Kang, Yeon Soo Kim, Ji-Ye Kim.

  A schwannoma is a tumor that arises from the Schwann cells of the peripheral nerves. Primary pulmonary schwannomas are extremely rare, although they can occur anywhere in the body. Symptoms of endobronchial schwannoma vary depending upon the extent of bronchi blockage by the tumor. Schwannoma is a benign tumor. However, there is a risk of recurrence if a lesion that has developed extraluminal growth is incompletely resected. Here, a 76-year-old female patient presented with dyspnea and cough. An endobronchial tumor was identified originating from the left lower lobe bronchus and had collapsed the left lower lobe and grown to block most of the left main bronchus. Video-assisted thoracic surgery was performed to resect the left lower lobe. The tumor was diagnosed as an ancient schwannoma.

Keywords:  bronchoscopy; endobronchial ancient schwannoma; video-assisted thoracic surgery

DOI:  https://doi.org/10.1093/jscr/rjae140
Cancers (Basel). 2024 Feb 29. pii: 994. [Epub ahead of print]16(5):

The NF1+/- Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant Transformation.

Emily E White, Steven D Rhodes.

  Neurofibromatosis type 1 (NF1) is a common genetic disorder resulting in the development of both benign and malignant tumors of the peripheral nervous system. NF1 is caused by germline pathogenic variants or deletions of the NF1 tumor suppressor gene, which encodes the protein neurofibromin that functions as negative regulator of p21 RAS. Loss of NF1 heterozygosity in Schwann cells (SCs), the cells of origin for these nerve sheath-derived tumors, leads to the formation of plexiform neurofibromas (PNF)-benign yet complex neoplasms involving multiple nerve fascicles and comprised of a myriad of infiltrating stromal and immune cells. PNF development and progression are shaped by dynamic interactions between SCs and immune cells, including mast cells, macrophages, and T cells. In this review, we explore the current state of the field and critical knowledge gaps regarding the role of NF1(Nf1) haploinsufficiency on immune cell function, as well as the putative impact of Schwann cell lineage states on immune cell recruitment and function within the tumor field. Furthermore, we review emerging evidence suggesting a dueling role of Nf1+/- immune cells along the neurofibroma to MPNST continuum, on one hand propitiating PNF initiation, while on the other, potentially impeding the malignant transformation of plexiform and atypical neurofibroma precursor lesions. Finally, we underscore the potential implications of these discoveries and advocate for further research directed at illuminating the contributions of various immune cells subsets in discrete stages of tumor initiation, progression, and malignant transformation to facilitate the discovery and translation of innovative diagnostic and therapeutic approaches to transform risk-adapted care.

Keywords:  Schwann cells; T cells; atypical neurofibroma; biomarkers; immune microenvironment; immunotherapy; macrophages; malignant peripheral nerve sheath tumor; mast cells; neurofibromatosis type 1 (NF1); plexiform neurofibroma

DOI:  https://doi.org/10.3390/cancers16050994
Cureus. 2024 Feb;16(2): e53855

Laser Interstitial Thermal Therapy as a Treatment Option for Malignant Peripheral Nerve Sheath Tumor Metastases to the Brain: A Case Report.

Annie Pico, Isabel L Bauer, Kristin Nosova, Ashley Kern, Robert Bina.

  We present the unique case of a 60-year-old female with neurofibromatosis type 1 (NF1) who underwent laser interstitial thermal therapy (LITT) for metastatic malignant peripheral nerve sheath tumor (MPNST) of the brain. She presented to the emergency room complaining of one week of dysarthria and facial droop. An MRI of the brain demonstrated a homogeneously enhancing left frontal mass; although rare, given her history of pulmonary MPNST, brain invasion was considered likely. No generally accepted guidelines for the treatment of MPNST with cerebral metastases exist; however, LITT was chosen due to tumor morphology and proximity to eloquent brain structures. She did not experience any new or worsening neurological deficits post-operatively. Post-ablation MRI showed white matter edema surrounding the lesion, which is consistent with previously reported cases. This case illustrates the use of LITT for cytoreduction for rare brain metastases located near eloquent brain structures.

Keywords:  laser interstitial thermal therapy; malignant peripheral nerve sheath tumor; malignant peripheral nerve sheath tumors; peripheral nerve disorders; stereotactic laser ablation

DOI:  https://doi.org/10.7759/cureus.53855
J Gastrointest Oncol. 2024 Feb 29. 15(1): 458-467

Inhibition of GABAergic neurons in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice.

Ning-Ning Ji, Zhi-Yan Li, Shuang Cao, Bei Pei, Chen-Yu Jin, Yi-Fan Li, Peng Mao, Hong Jiang, Bi-Fa Fan, Ming Xia.

   Background: For patients with pancreatic cancer, visceral pain is a debilitating symptom that significantly compromises their quality of life. Unfortunately, the lack of effective treatment options can be attributed to our limited understanding of the neural circuitry underlying this phenomenon. The primary objective of this study is to elucidate the fundamental mechanisms governing visceral pain induced by pancreatic cancer in murine models.
Methods: A mouse model of pancreatic cancer visceral pain was established in C57BL/6N mice through the intrapancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were employed to evaluate visceral pain, whereas the in vitro electrophysiological patch-clamp technique was utilized to record the electrophysiological activity of GABAergic neurons. Specific neuron ablation and chemogenetics methods were employed to investigate the involvement of GABAergic neurons in pancreatic cancer-induced visceral pain.
Results: In vitro electrophysiological results showed that the firing frequency of GABAergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was decreased. Specific destruction of GABAergic neurons in the PVN exacerbated visceral pain induced by pancreatic cancer. Chemogenetics activation of GABAergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer.
Conclusions: GABAergic neurons located in PVN play a crucial role in precipitating visceral pain induced by pancreatic cancer in mice, thereby offering novel insights for identifying effective targets to treat pancreatic cancer-related visceral pain.

Keywords:  GABAergic neurons; mice; paraventricular nucleus of the hypothalamus (PVN); visceral pain induced by pancreatic cancer

DOI:  https://doi.org/10.21037/jgo-24-50
Oncogene. 2024 Mar 13.

p53 modulates kinase inhibitor resistance and lineage plasticity in NF1-related MPNSTs.

Jamie L Grit, Lauren E McGee, Elizabeth A Tovar, Curt J Essenburg, Emily Wolfrum, Ian Beddows, Kaitlin Williams, Rachael T C Sheridan, Joshua L Schipper, Marie Adams, Menusha Arumugam, Thomas Vander Woude, Sharavana Gurunathan, Jeffrey M Field, Julia Wulfkuhle, Emanuel F Petricoin, Carrie R Graveel, Matthew R Steensma.

Malignant peripheral nerve sheath tumors (MPNSTs) are chemotherapy resistant sarcomas that are a leading cause of death in neurofibromatosis type 1 (NF1). Although NF1-related MPNSTs derive from neural crest cell origin, they also exhibit intratumoral heterogeneity. TP53 mutations are associated with significantly decreased survival in MPNSTs, however the mechanisms underlying TP53-mediated therapy responses are unclear in the context of NF1-deficiency. We evaluated the role of two commonly altered genes, MET and TP53, in kinome reprograming and cellular differentiation in preclinical MPNST mouse models. We previously showed that MET amplification occurs early in human MPNST progression and that Trp53 loss abrogated MET-addiction resulting in MET inhibitor resistance. Here we demonstrate a novel mechanism of therapy resistance whereby p53 alters MET stability, localization, and downstream signaling leading to kinome reprogramming and lineage plasticity. Trp53 loss also resulted in a shift from RAS/ERK to AKT signaling and enhanced sensitivity to MEK and mTOR inhibition. In response to MET, MEK and mTOR inhibition, we observed broad and heterogeneous activation of key differentiation genes in Trp53-deficient lines suggesting Trp53 loss also impacts lineage plasticity in MPNSTs. These results demonstrate the mechanisms by which p53 loss alters MET dependency and therapy resistance in MPNSTS through kinome reprogramming and phenotypic flexibility.

DOI: https://doi.org/10.1038/s41388-024-03000-9
bioRxiv. 2024 Mar 01. pii: 2024.02.26.582088. [Epub ahead of print]

Retrograde tracing of breast cancer-associated sensory neurons.

Svetllana Kallogjerovic, Inés Velázquez-Quesada, Rutva Hadap, Bojana Gligorijevic.

Breast cancer is one of the leading causes of mortality among women. The tumor microenvironment, consisting of host cells and extracellular matrix, has been increasingly studied for its interplay with cancer cells, and the resulting effect on tumor progression. While the breast is one of the most innervated organs in the body, the role of neurons, and specifically sensory neurons, has been understudied, mostly for technical reasons. One of the reasons is the anatomy of sensory neurons: sensory neuron somas are located in the spine, and their axons can extend longer than a meter across the body to provide innervation in the breast. Next, neurons are challenging to culture, and there are no cell lines adequately representing the diversity of sensory neurons. Finally, sensory neurons are responsible for transporting several different types of signals to the brain, and there are many different subtypes of sensory neurons. The subtypes of sensory neurons which innervate and interact with breast tumors are unknown. To establish the tools for labeling and subtyping neurons that interact with breast cancer cells, we utilized two retrograde tracer's standards in neuroscience, wheat-germ agglutinin (WGA) and cholera toxin subunit B (CTB). In vitro , we employed primary sensory neurons isolated from mouse dorsal root ganglia, cultured in a custom-built microfluidic device DACIT, that mimics the anatomical compartmentalization of the sensory neuron's soma and axons. In vivo , we utilized both syngeneic and transgenic mouse models of mammary carcinoma. We show that CTB and WGA trace different but overlapping sensory neuronal subpopulations: while WGA is more efficient in labeling CGRP+ neurons, CTB is superior in labeling the NF200+ neurons. Surprisingly, both tracers are also taken up by a significant population of breast cancer cells, both in vitro and in vivo . In summary, we have established methodologies for retrograde tracing of sensory neurons interacting with breast cancer cells. Our tools will be useful for future studies of breast tumor innervation, and development of therapies targeting breast cancer-associated neuron subpopulations of sensory neurons.

DOI: https://doi.org/10.1101/2024.02.26.582088
Mol Carcinog. 2024 Mar 14.

Ligand-gated ion channels as potential biomarkers for ADT-mediated cognitive decline in prostate cancer patients.

Shiv Verma, Vaibhav Singh, VijayKrishna Nagampalli, Lee E Ponsky, Chiang-Shan R Li, Herta Chao, Sanjay Gupta.

  Men with prostate cancer are at increased risk of developing cognitive decline by the use of second-generation androgen signaling inhibitors. To date, reliable and sensitive biomarkers that could distinguish men at high risk of cognitive dysfunction under androgen deprivation therapy (ADT) have not been characterized. We used high-throughput transcriptional profiling utilizing human prostate cancer cell culture models mimicking ADT, biomarker selection using minimal common oncology data elements-cytoscape, and bioinformatic analyses employing Advaita® iPathwayGuide and DisGeNET for identification of disease-related gene associations. Validation analysis of genes was performed on brain neuronal and glial cells by quantitative real-time polymerase chain reaction assay. Our systematic analysis of androgen deprivation-associated genes involved multiple biological processes, including neuroactive ligand-receptor interaction, axon guidance, cytokine-cytokine receptor interaction, and metabolic and cancer signaling pathways. Genes associated with neuroreceptor ligand interaction, including gamma-aminobutyric acid (GABA) A and B receptors and nuclear core proteins, were identified as top upstream regulators. Functional enrichment and protein-protein interaction network analysis highlighted the role of ligand-gated ion channels (LGICs) and their receptors in cognitive dysfunction. Gene-disease association assigned forgetfulness, intellectual disability, visuospatial deficit, bipolar disorder, and other neurocognitive impairment with upregulation of type-1 angiotensin II receptor, brain-derived neurotrophic factor, GABA type B receptor subunit 2 (GABBR2), GABRA3, GABRA5, GABRB1, glycine receptor beta, glutamate ionotropic receptor N-methyl-D-aspartate receptor (NMDA) type subunit 1, glutamate ionotropic receptor NMDA type subunit 2D, 5-hydroxytryptamine receptor 1D, interferon beta 1, and nuclear receptor subfamily 3 group C member 1 as top differentially expressed genes. Validation studies of brain glial cells, neurons, and patients on ADT demonstrated the association of these genes with cognitive decline. Our findings highlight LGICs as potential biomarkers for ADT-mediated cognitive decline. Further validation of these biomarkers may lead to future practical clinical use.

Keywords:  androgen deprivation therapy; biomarkers; brain deficits; cognitive decline; prostate cancer

DOI:  https://doi.org/10.1002/mc.23708
Kyobu Geka. 2024 Feb;77(2): 115-120

[Surgically Resected Cases of Mediastinal Ganglioneuroma Detected in Adults].

Masayo Nishida, Mikito Suzuki, Makoto Hirai, Tohohiro Imoto, Reiko Shimizu, Masahiko Harada, Tsunekazu Hishima, Hirotoshi Horio.

A ganglioneuroma is a rare, benign, neurogenic tumor originating from the sympathetic ganglion. Mediastinal ganglioneuroma are mostly detected in children, typically around 10 years of age, and are rarely identified in adults. Herein, we report two surgically resected cases of mediastinal ganglioneuroma in adults. In Case 1, a 53-year-old man, without any symptom, underwent a computed tomography, revealing a 3.2 cm well-defined paravertebral superior mediastinal tumor with long craniocaudal axis. In case 2, a 29-year-old woman presented with newly-developed ptosis and a history of left-sided facial hypohidrosis since the age of 10. Chest computed tomography (CT) revealed a 7.8 cm well-defined paravertebral superior mediastinal tumor with long craniocaudal axis. Both patients were initially suspected to have neurogenic tumors, particularly schwannomas. They underwent mediastinal tumor resections, requiring sympathetic nerve trunk dissection. Pathological examination confirmed the diagnosis of ganglioneuromas in both cases. Mediastinal ganglioneuroma must be differentiated from schwannoma, the most common neurogenic tumor in adults. Unlike schwannoma, ganglioneuroma cannot be enucleated, therefore attention should be focused on complications associated with sympathetic nerve trunk dissection, such as Horner's syndrome, hyperhidrosis, and arrhythmia. Identifying this rare entity and its characteristic imaging aids in preoperative differentiation, strategizing surgical approaches, and predicting complications.
Skeletal Radiol. 2024 Mar 11.

High-frequency ultrasound imaging findings in the diagnosis of segmental schwannomatosis of the ulnar nerve: case report and literature review.

Shuang Li, Jingwen Han, Xiaoping Zhang, Yunfeng Qi, Jie Du, Lirong Zhao.

  Schwannomatosis is characterized by the development of multiple schwannomas without evidence of vestibular tumors. Segmental schwannomatosis is defined as being limited to one limb or five or fewer contiguous segments of the spine. We report a case of a 20-year-old male with the painful masses of the left upper extremity with associated numbness and paresthesia in the ulnar nerve distribution. The high-frequency ultrasound showed that the ulnar nerve fascicles were enlarged and expanded with beadlike growth. The patient underwent surgery twice and all the tumors were pathologically confirmed to be schwannomas. Together, the medical history, imaging, and pathology findings indicated the diagnosis of segmental schwannomatosis. By the imaging diagnostic tools, MRI is the most commonly used in assistance with diagnosis of segmental schwannomatosis while high-frequency ultrasonography is rare. In this paper, we discuss the value of high-frequency ultrasonography in the diagnosis of this rare disease. This case report provides a deeper understanding of segmental schwannomatosis and may help improve the accuracy of preoperative diagnosis.

Keywords:  Diagnosis; High-frequency ultrasound; Segmental schwannomatosis; Ulnar nerve

DOI:  https://doi.org/10.1007/s00256-024-04645-z
bioRxiv. 2024 Mar 01. pii: 2024.02.26.582218. [Epub ahead of print]

DACIT: Device for Axon - Cancer cell Interaction Testing in 2D and 3D.

Ines Velazquez-Quesada, Kara Allison, Vahid Alizadeh, Natasha Hesketh, Gareth Thomas, Erkan Tuzel, Bojana Gligorijevic.

In this protocol, we describe steps to design, fabricate and use the Device for Axon and Cancer cell Interaction Testing (DACIT) in 2D and in 3D. In the first section, we detail steps to generate the mask, the master and the smooth-on mold. Next, we describe the step-by-step protocol for fabricating the DACIT, loading sensory neurons and cancer cells in 2D or 3D. We compare axonogenesis using PC-12 cell line and primary embryonic or adult sensory neurons, demonstrating the superior neurite growth in primary cells. We demonstrate DACIT can be used to compartmentalize neuronal soma and axons and expose them to different conditions, or to form a temporary gradient of neurotransmitter. Finally, we show that DACIT can be used to measure spheroid invasion in 3D in the presence of axons.

DOI: https://doi.org/10.1101/2024.02.26.582218
Cancers (Basel). 2024 Feb 26. pii: 944. [Epub ahead of print]16(5):

Characteristics of Early Pancreatic Cancer: Comparison between Stage 1A and Stage 1B Pancreatic Cancer in Multicenter Clinical Data Warehouse Study.

Hyo Suk Kim, Young Hoon Choi, Jae Sin Lee, Ik Hyun Jo, Sung Woo Ko, Kyu Hyun Paik, Hyun Ho Choi, Han Hee Lee, Yeon Soo Lim, Chang Nyol Paik, In Seok Lee, Jae Hyuck Chang.

   BACKGROUND: Little is known about the characteristics of early pancreatic cancer. We aimed to identify the characteristics, clues for early detection, and prognostic factors for early pancreatic cancer by analyzing a large number of patients with stage 1 pancreatic cancer.
METHODS: A clinical data warehouse that includes databases of all the medical records of eight academic institutions was used to select and analyze patients with pancreatic cancer that had been diagnosed from January 2010 to May 2023.
RESULTS: In total, 257 stage 1 pancreatic cancer patients were included. There were 134 men (52%), and the average age was 67.2 ± 9.9 years. Compared to patients with stage 1B pancreatic cancer (2-4 cm), patients with stage 1A pancreatic cancer (≤2 cm) had more tumors in the body and tail than in the head (p = 0.028), more new-onset diabetes and less old diabetes (p = 0.010), less jaundice (p = 0.020), more follow-up of IPMN (intraductal papillary mucinous neoplasm, p = 0.029), and more histories of acute pancreatitis (p = 0.013). The pathological findings showed that stage 1A pancreatic cancer involved more IPMNs (p < 0.001) and lower pancreatic intraepithelial neoplasia (p = 0.004). IPMN was present in all 13 pancreatic tumors that were smaller than 1 cm. In multivariate analysis, positive resection margin (odds ratio [OR] 1.536, p = 0.040), venous invasion (OR 1.710, p = 0.010), and perineural invasion (OR 1.968, p = 0.002) were found to be risk factors affecting disease-free survival, while old diabetes (odds ratio [OS] 1.981, p = 0.003) and perineural invasion (OR 2.270, p = 0.003) were found to be risk factors affecting overall survival.
CONCLUSIONS: IPMN is closely associated with early pancreatic cancer and may provide an opportunity for early detection. The presence of perineural invasion was a crucial prognostic factor for both overall and disease-free survival in patients with stage 1 pancreatic cancer.

Keywords:  early detection of cancer; pancreatic cancer; pancreatic intraductal neoplasm; prognosis; survival

DOI:  https://doi.org/10.3390/cancers16050944