bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2024–12–22
ten papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Investigation of the correlation between AGRN expression and perineural invasion in colon cancer.
  2. 68Ga-PSMA PET/CT-Based Model Predicts Perineural Invasion of Prostate Cancer with Whole-Mount Sections.
  3. Capsaicin-induced Ca2+ overload and ablation of TRPV1-expressing axonal terminals for comfortable tumor immunotherapy.
  4. Preoperative prediction of microvascular/nerve invasion in locally advanced gastric cancer by differentiation and enhanced CT features.
  5. Exploring Shared Targets in Cancer Immunotherapy and Cancer-Induced Bone Pain: Insights from Preclinical Studies.
  6. Genetics of Constant and Severe Pain in the NAPS2 Cohort of Recurrent Acute and Chronic Pancreatitis Patients.
  7. Lung Cancer with Brain Metastasis-Treatment Strategies and Molecular Characteristics.
  8. Recurrent Ulnar Nerve Schwannoma in the Cubital Tunnel Elbow: A Rare Presentation and Surgical Management.
  9. Axillary Peripheral Nerve Schwannoma: A Rare Occurrence in the Torso.
  10. Differential diagnosis of submucosal gastric tumors: gastric schwannomas misdiagnosed as GISTs.
  1. Front Mol Biosci. 2024 ;11 1510478
    Investigation of the correlation between AGRN expression and perineural invasion in colon cancer.
    Lei Chen, Haijia Zhang, Kaiyue Gao, Fanqi Meng, Funing Yang, Jiannan Li, Lijie Wang, Jiandong Tai.
       Background and Purpose: Colon cancer is one of the most common gastrointestinal malignancies. According to the traditional view, the primary modes of transmission include direct dissemination, hematogenous metastasis, and lymph node metastasis. In recent years, the role of perineural invasion (PNI) in the spread and metastasis of tumors has received immense attention. However, there are still relatively few reports on the potential mechanisms and biomarkers of PNI occurrence and development in colon cancer.
    Method: We identified genes linked to the onset and progression of PNI in colon cancer using bioinformatics tools and extensive databases. Gene function enrichment analysis was used to explore the potential roles of these genes in tumor proliferation, invasion, and PNI. A collection of postoperative pathological specimens from colon cancer patients who underwent surgery, related clinicopathological data, and immunohistochemistry were used to validate AGRN expression in PNI tissues.
    Results: Bioinformatics analysis revealed that AGRN is overexpressed in colon cancer tissues and correlates with poor patient prognosis. The findings from gene association and enrichment studies indicate that AGRN and its associated genes may play a role in PNI development and progression in colon cancer by simultaneously enhancing tumor cell invasion and neural cell growth. Immunohistochemical analysis of clinical samples confirmed that AGRN expression is elevated in colon cancer tissues with PNI.
    Conclusion: We found that AGRN is significantly overexpressed in colon cancer tissues exhibiting PNI and is linked to poor patient survival. AGRN and its related genes may contribute to PNI by promoting tumor cell invasion and neural cell growth. Hence, AGRN may play a crucial role in the initiation and progression of PNI in colon cancer.
    Keywords:  AGRN; bioinformatics; colon cancer; immunohistochemistry; perineural invasion
    DOI:  https://doi.org/10.3389/fmolb.2024.1510478
  2. Mol Imaging Biol. 2024 Dec 16.
    68Ga-PSMA PET/CT-Based Model Predicts Perineural Invasion of Prostate Cancer with Whole-Mount Sections.
    Jie Gao, Yao Fu, Kuiqiang He, Qinfeng Xu, Feng Wang, Hongqian Guo.
       PURPOSE: To develop a novel risk model incorporating 68Ga-PSMA PET/CT parameters for prediction of perineural invasion (PNI) of prostate cancer (PCa).
    METHODS: The study retrospectively enrolled 192 PCa patients with preoperative multiparametric MRI, 68Ga-PSMA PET/CT and radical specimen. Imaging parameters were derived from both mpMRI and PET/CT images. S100 immunohistochemistry staining was conducted to evaluate PNI of PCa. Significant predictors were derived with univariate and multivariate logistic regression analyses, and the PNI-risk nomogram was constructed with significant predictors. Internal discrimination validation was performed with receiver operating characteristic analysis. Calibration curves were plotted, decision curve and clinical impact curve analysis were performed for clinical benefit exploration.
    RESULTS: With the median peritumoral nerve density of 6, patients were stratified as low-PNI group (nerve density < 6, n = 78, 40.6%) and high-PNI group (nerve density ≥ 6, n = 114, 59.4%). Compared with low-PNI PCa, high-PNI PCa harbored significantly larger imaging lesion diameter (P < 0.001), higher PI-RADS score (P = 0.009), higher SUVmax (P < 0.001), larger tumor diameter (P = 0.024) and higher Gleason grade group (P < 0.001). Further, with univariate and multivariate analyses, imaging lesion diameter (OR 2.98, 95% CI 1.73-5.16, P = 0.004) and SUVmax (OR 3.59, 95%CI 2.32-5.55, P < 0.001) and were identified as independent predictors for PNI in PCa, and a PNI-risk nomogram incorporating these two predictors was constructed. The PNI-risk nomogram demonstrated considerable calibration (mean absolute error 0.026) and discrimination (area under the curve = 0.889, sensitivity 73.1%, specificity 97.4%) abilities, harboring net benefits with threshold probabilities range from 0 to 0.80.
    CONCLUSION: 68Ga-PSMA PET/CT-based model could effectively predict the perineural invasion of PCa. These results may help with the decision-making on active surveillance, focal therapy and surgery approach. Additionally, patients suspicious of high-density PNI PCa should receive more radical treatment than low-PNI PCa.
    Keywords:   68Ga-PSMA PET/CT; Nerve; Nomogram; Perineural Invasion; Prostate Cancer
    DOI:  https://doi.org/10.1007/s11307-024-01974-2
  3. Nanoscale. 2024 Dec 17.
    Capsaicin-induced Ca2+ overload and ablation of TRPV1-expressing axonal terminals for comfortable tumor immunotherapy.
    Jian Sun, Deqiang Wang, Yiying Wei, Danyang Wang, Zhengkun Ji, Wanru Sun, Xin Wang, Pingyu Wang, Nicola Paccione Basmadji, Eider Larrarte, José Luis Pedraz, Murugan Ramalingam, Shuyang Xie, Ranran Wang.
      As a common malignancy symptom, cancer pain significantly affects patients' quality of life. Approximately 60%-90% of patients with advanced cancer experience debilitating pain. Therefore, a comprehensive treatment system that combines cancer pain suppression and tumor treatment could provide significant benefits for these patients. Here, we designed a manganese oxide (MnO2)/Bovine serum albumin (BSA)/polydopamine (PDA) composite nanoplatform internally loaded with capsaicin for cancer pain suppression and immunotherapy. MBD&C nanoparticles (NPs) can ablate tumor-innervated sensory nerve fibers via Transient receptor potential vanilloid 1 (TRPV1) channels, thereby reducing the pain caused by various inflammatory mediators. The ablation of TRPV1+ nerve terminals can also decrease the secretion of calcitonin gene-related peptide (CGRP) and substance P (SP) in sensory nerve fibers, thus reducing the tumor pain and inhibit tumor progression. MBD&C can promote calcium influx by activating overexpressed TRPV1 channels on the tumor membrane surface, thereby achieving cancer immunotherapy induced by endogenous Ca2+ overloading. In addition, MnO2 NPs can alleviate tumor hypoxia and mitigate the immunosuppressive tumor microenvironment (TME). Ultimately, this treatment system with dual capabilities of inhibiting tumor growth and relieving cancer pain makes comfortable tumor therapy feasible and paves the way for the development of patient-centered approaches to cancer treatment in the future.
    DOI:  https://doi.org/10.1039/d4nr04454a
  4. Medicine (Baltimore). 2024 Dec 13. 103(50): e40816
    Preoperative prediction of microvascular/nerve invasion in locally advanced gastric cancer by differentiation and enhanced CT features.
    Xiu-Chun Ren, Pan Liang.
      The purpose of the article is to determine whether differentiation and enhanced CT features can preoperatively predict microvascular/nerve invasion in locally advanced gastric cancer. Retrospective analysis of the CT and pathological data of 325 patients with locally advanced gastric cancer confirmed by pathology in our hospital from July 2011 to August 2023. The patient's age, gender, tumor location, T stage, N stage, TNM stage, differentiation, Lauren classification, as well as tumor thickness, tumor longest diameter, plain CT value, arterial CT value, venous CT value, arterial phase enhancement rate, and venous phase enhancement rate were assessed. This study included a total of 325 patients with locally advanced gastric cancer and 189 patients (58.15%) with microvascular/nerve invasion. The results of the univariate analysis showed that gender, location, T stage, N stage, TNM stage, differentiation, Lauren classification, tumor thickness, and longest diameter of the tumor were associated with microvascular/nerve invasion (P < .05). Multivariate analysis suggested that TNM stage and differentiation were independent risk factors for microvascular/nerve invasion. The receiver operating characteristic analysis showed that the diagnostic efficacy of the combined parameter of TNM stage and differentiation was better than that of the single parameter, in which area under the curve, sensitivity, and specificity were 0.819 (95%CI: 0.770-0.867), 66.7%, and 83.8%, respectively. Differentiation and enhanced CT are helpful in predicting whether microvascular/nerve invasion occurs in locally advanced gastric cancer before operation, especially the combined parameters of TNM stage and differentiation.
    DOI:  https://doi.org/10.1097/MD.0000000000040816
  5. Cancer Lett. 2024 Dec 15. pii: S0304-3835(24)00794-8. [Epub ahead of print] 217399
    Exploring Shared Targets in Cancer Immunotherapy and Cancer-Induced Bone Pain: Insights from Preclinical Studies.
    Ruofan Zhang, Yachen Yang, Xiang Li, Chunmeng Jiao, Mengping Lou, Wenli Mi, Qi-Liang Mao-Ying, Yuxia Chu, Yanqing Wang.
      Cancer casts a profound shadow on global health, with pain emerging as one of the dominant and severe complications, particularly in advanced stages. The effective management of cancer-induced pain remains an unmet need. Emerging preclinical evidence suggests that targets related to tumor immunotherapy may also modulate cancer-related pain pathways, thus offering a promising therapeutic direction. This review, focusing on more than ten molecular targets that link cancer immunotherapy and cancer-induced bone pain, underscores their potential to tackle both aspects in the context of comprehensive cancer care. Emphasizing factors such as types of cancer, drug administration methods, and sex differences in the analgesic efficacy of immunotherapeutic agents provides neuroscientific insights into personalized pain management for patients with cancer.
    Keywords:  Cancer immunotherapy; Cancer neuroscience; Cancer-induced bone pain; Tumor neurobiology
    DOI:  https://doi.org/10.1016/j.canlet.2024.217399
  6. J Pain. 2024 Dec 12. pii: S1526-5900(24)00732-6. [Epub ahead of print] 104754
    Genetics of Constant and Severe Pain in the NAPS2 Cohort of Recurrent Acute and Chronic Pancreatitis Patients.
    NAPS2⁎ study group
      Recurrent acute and chronic pancreatitis (RAP, CP) are complex, progressive inflammatory diseases with variable pain experiences impacting patient function and quality of life. The genetic variants and pain pathways in patients contributing to most severe pain experiences are unknown. We used previously genotyped individuals with RAP/CP from the North American Pancreatitis Study II (NAPS2) of European Ancestry for nested genome-wide associated study (GWAS) for pain-severity, chronicity, or both. Lead variants from GWAS were determined using FUMA. Loci with p<1e-5 were identified for post-hoc candidate identification. Transcriptome-wide association studies (TWAS) identified loci in cis and trans to the lead variants. Serum from phenotyped individuals with CP from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies (PROCEED) was assessed for BDNF levels using Meso Scale Discovery Immunoassay. We identified four pain systems defined by candidate genes: 1) Pancreas-associated injury/stress mitigation genes include: REG gene cluster, CTRC, NEURL3 and HSF22. 2) Neural development and axon guidance tracing genes include: SNPO, RGMA, MAML1 and DOK6 (part of the RET complex). 3) Genes linked to psychiatric stress disorders include TMEM65, RBFOX1, and ZNF385D. 4) Genes in the dorsal horn pain-modulating BDNF/neuropathic pathway included SYNPR, NTF3 and RBFOX1. In an independent cohort BDNF was significantly elevated in patients with constant-severe pain. Extension and expansion of this exploratory study may identify pathway- and mechanism-dependent targets for individualized pain treatments in CP patients. PERSPECTIVE: Pain is the most distressing and debilitating feature of chronic pancreatitis. Yet many patients with chronic pancreatitis have little or no pain. The North American Pancreatitis Study II (NAPS2) includes over 1250 pancreatitis patients of all progressive stages with all clinical and phenotypic characteristics carefully recorded. Pain did not correlate well with disease stage, inflammation, fibrosis or other features. Here we spit the patients into groups with the most severe pain and/or chronic pain syndromes and compared them genetically with patients reporting mild or minimal pain. Although some genetic variants associated with pain were expressed in cells (1) of the pancreas, most genetic variants were linked to genes expressed in the nervous system cells associated with (2) neural development and axon guidance (as needed for the descending inhibition pathway), (3) psychiatric stress disorders, and (4) cells regulating sensory nerves associated with BDNF and neuropathic pain. Similar and overlapping genetic variants in systems 2 -4 are also seen in pain syndromes form other organs. The implications for treating pancreatic pain are great in that we can no longer focus on just the pancreas. Furthermore, new treatments designed for pain disorders in other tissues may be effective in some patient with pain syndromes from the pancreas. Further research is needed to replicate and extend these observations so that new, genetics-guided rational treatments can be developed and delivered.
    Keywords:  Chronic Pain; Genetics; Inflammation; Neuralgia; Pancreatitis
    DOI:  https://doi.org/10.1016/j.jpain.2024.104754
  7. J Clin Med. 2024 Dec 03. pii: 7371. [Epub ahead of print]13(23):
    Lung Cancer with Brain Metastasis-Treatment Strategies and Molecular Characteristics.
    Shuai Wang, Matan Uriel, Haiying Cheng.
      Lung cancer is a leading cause of brain metastases (BMs), with 10-20% of patients with non-small cell lung cancer (NSCLC) presenting with BMs at diagnosis and 25-50% developing them over the course of their disease. Historically, BMs have posed significant therapeutic challenges, partly due to the blood brain barrier (BBB), which restricts drug penetration to the central nervous system. Consequently, BMs were initially managed with local treatments, including surgical resection, stereotactic radiosurgery, and whole brain radiation therapy. In recent years, however, systemic treatments for BMs have advanced significantly, particularly with the development of molecularly-targeted therapies and immunotherapies. The discovery of driver mutations and the development of novel tyrosine kinase inhibitors (TKIs) have yielded encouraging intracranial responses in NSCLC patients with actionable genetic alterations (e.g., EGFR, ALK, ROS1). Genomic profiling has also suggested genetic heterogeneity between BMs and primary sites. Immunotherapies, alone or in combination with other treatments, have demonstrated promising results in NSCLC with BMs, although most clinical trials have included only selected patients with asymptomatic or previously treated BMs. In this review, we discuss the molecular and immune characteristics of NSCLC with BMs, analyze intracranial efficacy findings from clinical trials, and explore treatment strategies for lung cancer patients with BMs.
    Keywords:  brain metastases; immunotherapy; lung cancer; targeted therapy
    DOI:  https://doi.org/10.3390/jcm13237371
  8. Cureus. 2024 Nov;16(11): e73631
    Recurrent Ulnar Nerve Schwannoma in the Cubital Tunnel Elbow: A Rare Presentation and Surgical Management.
    Pankaj Kabra, Mende Vikram Kumar Yadav, Shravan Peddamadyam, Sai Praneeth Bathineedi, Kovuri Yamini.
      Schwannoma is a benign tumor arising from Schwann cells of peripheral nerves. Although recurrence is rare, this case report highlights a unique instance of recurrent ulnar nerve schwannoma in a 76-year-old construction worker, emphasizing the complexities of surgical management. The patient presented to our orthopedic clinic with persistent pain and tingling in the medial aspect of his left forearm and hand for the past two years. His medical history included bilateral ulnar nerve schwannoma excision at the cubital tunnel level 20 years prior. Examination revealed a firm, non-tender swelling measuring 5 × 5 cm on the medial side of the left distal arm, with neurological assessment indicating reduced sensation in the little finger and medial half of the ring finger, as well as intrinsic hand muscle weakness. His preoperative Disabilities of the Arm, Shoulder, and Hand (DASH) score was 65, reflecting substantial functional limitations. Preoperative nerve conduction studies confirmed ulnar nerve damage, and MRI indicated a tumor originating from the left ulnar nerve. Given the tumor's increasing size, surgical excision was done. The procedure involved careful dissection around the elbow to isolate the ulnar nerve, significantly affected by fibrosis from prior surgeries. We performed macro neurolysis, which decompresses larger segments of the nerve, and micro neurolysis, which allows for precise intervention on specific segments, to effectively address the challenges presented by the scar tissue. Anterior transposition of the ulnar nerve was conducted to place it in an unscarred area, reducing compression and promoting nerve function. The postoperative biopsy confirmed a benign schwannoma characterized by localized Antoni A and Antoni B areas. Six months post surgery, the patient reported complete resolution of symptoms, with grip strength improving to approximately 95% of normal and a postoperative DASH score of 25. Follow-up assessments showed enhanced nerve function, with no signs of tumor recurrence over two years. This case underscores the challenges of managing recurrent ulnar nerve schwannoma and emphasizes the critical role of surgical intervention in preserving nerve function and improving patient outcomes. The successful management of this recurrence highlights the importance of meticulous surgical technique and thorough follow-up in ensuring long-term patient well-being.
    Keywords:  complications; diagnostic imaging; intraneural fibrosis; long-term follow-up; recurrence factors; recurrent schwannoma; surgical difficulties; surgical excision; ulnar nerve
    DOI:  https://doi.org/10.7759/cureus.73631
  9. Cureus. 2024 Nov;16(11): e73622
    Axillary Peripheral Nerve Schwannoma: A Rare Occurrence in the Torso.
    Ahmed Inayath Syed, Sachin Patil, Sneha Zakkir.
      A schwannoma is a benign, solitary, noninvasive, and encapsulated tumor that originates from Schwann cells of the peripheral nerve sheath commonly found in the head and neck. A rare case of a benign schwannoma in the axillary region of a 34-year-old male patient is presented here accompanied by a discussion on the known entities of peripheral nerve schwannoma as well as the clinical and radiological findings coupled with treatment techniques. The patient presented with a left axillary mass of seven years gradually progressing in size which is associated with pain in the left arm. There were no neurological deficits on examination. Ultrasound and soft tissue MRI were performed followed by fine-needle aspiration cytology (FNAC), and a decision was made to take the patient up for an excisional biopsy. Histopathology revealed a tumor composed of hyper- (Antoni A) and hypocellular (Antoni B) areas, while immunohistochemistry was positive for the S-100 protein, thus confirming the diagnosis of left axillary peripheral nerve schwannoma. With such nonspecific presentation and the added challenge of its rarity, an axillary schwannoma may be easily missed and mismanaged. Surgical excision and biopsy are recommended with an aim of preserving neurological function.
    Keywords:  axillary schwanomma; benign peripheral nerve sheath tumor; brachial plexus; brachial plexus schwannoma; excisional biopsy
    DOI:  https://doi.org/10.7759/cureus.73622
  10. J Surg Case Rep. 2024 Dec;2024(12): rjae793
    Differential diagnosis of submucosal gastric tumors: gastric schwannomas misdiagnosed as GISTs.
    Mutlu Unver, Suleyman Cağlar Ertekin, Eyüp Kebapcı, Mustafa Olmez, Erhan Ergin, Safak Ozturk, Erkan Sahin, Ragıp Ortac.
      Schwannomas commonly occur in the head and neck region but are rarely seen in the gastrointestinal tract; the stomach and small intestine are the most commonly involved sites. These tumors are usually misdiagnosed as gastrointestinal stromal tumors (GISTs) before histopathological confirmation due to radiological similarity. GI schwannomas show positivity for S100 protein and vimentin but are negative for CD 117 and CD 34, which helps in differentiating the tumor from GISTs. Case 1: a 70-year-old woman was referred to our hospital by complaints of abdominal pain and discomfort. Upper GI endoscopy demonstrated a protruding lesion at the lesser curvature of the gastric body, and fine-needle aspiration biopsy showed chronic inflammation without malignancy. Since the lesion was suspected to be GIST, this patient had surgery, and a gastric schwannoma was resected successfully. Case 2: a 66-year-old female with anemia and abdominal discomfort was found to have a submucosal elevated mass at the greater curvature of the antrum. Fine needle aspiration biopsy was suggestive of a spindle cell tumor resembling GIST. The patient underwent subtotal gastrectomy with Roux-en-Y reconstruction. Histopathology confirmed schwannoma. It is necessary to differentiate gastric schwannomas from other submucosal tumors of the stomach, especially GISTs. Surgical complete resection of schwannomas usually has a good prognosis with a low probability of recurrence. Though rare, gastric schwannomas should be included in the differential diagnosis of submucosal gastric tumors because the correct identification of this tumor type helps in proper management and evasion of unnecessary extensive surgery.
    Keywords:  differential diagnosis; gastric schwannoma; gastrointestinal stromal tumor (GIST); surgical resection
    DOI:  https://doi.org/10.1093/jscr/rjae793
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