bims-netuvo 2024-12-29 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2024–12–29
thirteen papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Nervous system contributions to small cell lung cancer: Lessons from diverse oncological studies.
Nervous system in colorectal cancer.
Liver Cancer Neuroscience: Regulating Liver Tumors via Selective Hepatic Vagotomy.
NGF-mediated crosstalk: unraveling the influence of metabolic deregulation on the interplay between neural and pancreatic cancer cells and its impact on patient outcomes.
Characterization of a Cancer-Induced Bone Pain Model for Use as a Model of Cancer Cachexia.
Primary pleural schwannoma: a rare case report.
Novel MRI signs for differentiating neurogenic and non-neurogenic peripheral nerve Tumors: Insights from Contrast-Enhanced magnetic resonance neurography.
Peripheral, central, and chemotherapy-induced neuropathic changes in pancreatic cancer.
Preoperative clinical and contrasted-enhanced CT features to predict perineural invasion in gallbladder carcinoma: focus on clinical T3-4 stage.
Interventional treatment of right lower lobe bronchial schwannoma under bronchoscopy: A case report and literature review.
The diagnosis and treatment of the epithelioid sarcomas involving the peripheral nerves.
Peripheral Neuropathy Instruments for Individuals with Cancer: A COSMIN-Based Systematic Review of Measurement Properties.
N-acetylcysteine prevents cisplatin-induced cognitive impairments in an ovarian cancer rat model.

Biochim Biophys Acta Rev Cancer. 2024 Dec 24. pii: S0304-419X(24)00183-5. [Epub ahead of print] 189252

Nervous system contributions to small cell lung cancer: Lessons from diverse oncological studies.

Shuangsi Liao, Kai Kang, Zhuoran Yao, You Lu.

  The nervous system plays a vital role throughout the entire lifecycle and it may regulate the formation, development and metastasis of tumors. Small cell lung cancer is a typical neuroendocrine tumor, and it is naturally equipped with neurotropism. In this review, we firstly summarize current preclinical and clinical evidence to demonstrate the reciprocal crosstalk among the nervous system, tumor, and tumor microenvironment in various ways, including neurotransmitter-receptor pathways, innervations of nerve fibers, different types of synapse formation by neurons, astrocytes, and cancer cells, neoneurogenesis. Futherly, we emphasize how the nervous system interacts with small cell lung cancer and discuss the limitations of current research methods for examining the interactions. We propose that integrating neuroscience, development biology, and tumor biology can be a promising direction to provide new insights into development and metastasis of small cell lung cancer and raise some novel treatment strategies.

Keywords:  Brian metastasis; Innervation; Nervous system; Neurotransmitter; Small cell lung cancer (SCLC); Tumor microenvironment (TME)

DOI:  https://doi.org/10.1016/j.bbcan.2024.189252
Cancer Lett. 2024 Dec 24. pii: S0304-3835(24)00826-7. [Epub ahead of print] 217431

Nervous system in colorectal cancer.

Chunjie Xu, Chunhui Jiang, Yuan Tian, Ye Liu, Hao Zhang, Zeyu Xiang, Hanbing Xue, Lei Gu, Qing Xu.

  A malignant tumor is a complex systemic disease involving the nervous system, which regulates nerve signals. Cancer neuroscience is a field that explores the interactions between tumors and the nervous system. The gastrointestinal tract is a typical peripheral organ with abundant neuroregulation and is regulated by the peripheral, enteric, and central nervous systems (PNS, ENS, and CNS, respectively). The physiological functions of the gastrointestinal tract are maintained via complex neuromodulation. Neuroregulatory imbalance is the primary cause of gastrointestinal diseases, including colorectal cancer (CRC). In CRC, there is a direct interaction between the nervous system and tumor cells. Moreover, this tumor-nerve interaction can indirectly regulate the tumor microenvironment, including the microbiota, immunity, and metabolism. In addition to the lower nerve centers, the stress response, emotion, and cognition represented by the higher nerve centers also participate in the occurrence and progression of CRC. Herein, we review some basic knowledge regarding cancer neuroscience and elucidate the mechanism underlying tumor-nerve interactions in CRC.

Keywords:  central nervous system; colorectal neoplasms; gastrointestinal diseases; thoracic nerves; tumor microenvironment

DOI:  https://doi.org/10.1016/j.canlet.2024.217431
Methods Protoc. 2024 Dec 11. pii: 99. [Epub ahead of print]7(6):

Liver Cancer Neuroscience: Regulating Liver Tumors via Selective Hepatic Vagotomy.

Kylynda C Bauer, Shadin Ghabra, Chi Ma, Lee Chedester, Tim F Greten.

  Both the prevalence and mortality of liver cancers continue to rise. Early surgical interventions, including liver transplantation or resection, remain the only curative treatment. Nerves in the periphery influence tumor growth within visceral organs. Emerging cancer neuroscience efforts linked parasympathetic vagus nerves with tumor pathology, underscoring the value of vagal nerve denervation methods within cancer mouse models. Here, we describe a selective hepatic vagotomy that largely maintains non-liver parasympathetic innervation in mice. To address vagal interactions in hepatic tumor pathology, we provide an adapted methodology utilizing an established liver metastatic model. We anticipate that this methodology will expand the burgeoning field of cancer neuroscience, enabling the study of the neuroimmune, neurometabolic, and/or nerve-microbiota interactions shaping liver cancer progression and treatment.

Keywords:  A20; hepatic vagotomy; liver cancer; metastases; parasympathetic nervous system; vagus

DOI:  https://doi.org/10.3390/mps7060099
Front Pharmacol. 2024 ;15 1499414

NGF-mediated crosstalk: unraveling the influence of metabolic deregulation on the interplay between neural and pancreatic cancer cells and its impact on patient outcomes.

Francesca Trentini, Virginia Agnetti, Martina Manini, Elisa Giovannetti, Ingrid Garajová.

  Neural invasion is one of the most common routes of invasion in pancreatic cancer and it is responsible for the high rate of tumor recurrence after surgery and the pain generation associated with pancreatic cancer. Several molecules implicated in neural invasion are also responsible for pain onset including NGF belonging to the family of neutrophins. NGF released by cancer cells can sensitize sensory nerves which in turn results in severe pain. NGF receptors, TrkA and P75NTR, are expressed on both PDAC cells and nerves, strongly suggesting their role in neural invasion. The crosstalk between the nervous system and cancer cells has emerged as an important regulator of pancreatic cancer and its microenvironment. Nerve cells influence the pancreatic tumor microenvironment and these interactions are important for cancer metabolism reprogramming and tumor progression. In this review, we summarized the current knowledge on the interaction between nerves and pancreatic cancer cells and its impact on cancer metabolism.

Keywords:  NGF; metabolism; neural invasion; pain; pancreatic cancer

DOI:  https://doi.org/10.3389/fphar.2024.1499414
Curr Issues Mol Biol. 2024 Nov 23. 46(12): 13364-13382

Characterization of a Cancer-Induced Bone Pain Model for Use as a Model of Cancer Cachexia.

Takuya Hasegawa, Kohichi Kawahara, Koji Sato, Yoshihisa Asano, Takehiko Maeda.

  Cancer cachexia is a debilitating syndrome characterized by progressive weight loss, muscle wasting, and systemic inflammation. Despite the prevalence and severe consequences of cancer cachexia, effective treatments for this syndrome remain elusive. Therefore, there is a greater need for well-characterized animal models to identify novel therapeutic targets. Certain manifestations of cachexia, such as pain and depression, have been extensively studied using animal models of cancer-induced bone pain (CIBP). In contrast, other aspects of cachexia have received less attention in these models. To address this issue, we established the CIBP model by injecting Lewis lung carcinoma into the intramedullary cavity of the femur, observed cachexia-related symptoms, and demonstrated the utility of this model as a preclinical platform to study cancer cachexia. This model accurately recapitulates key features of cancer cachexia, including weight loss, muscle atrophy, adipose tissue depletion, CIBP, and anxiety. These findings suggest that psychological factors, in addition to physiological and metabolic factors, play significant roles in cancer cachexia development. Our model offers a valuable resource for investigating the underlying mechanisms of cancer cachexia and for developing innovative therapeutic strategies that target physical and psychological components.

Keywords:  animal model; cancer cachexia; nutritional impact symptoms

DOI:  https://doi.org/10.3390/cimb46120797
J Med Life. 2024 Oct;17(10): 953-955

Primary pleural schwannoma: a rare case report.

Moaaz Amir, Salwa Sheikh.

  Schwannomas are peripheral nerve sheath tumors that rarely arise from autonomic nerves of the pleural lining. Most often, they present as slow-growing tumors and are asymptomatic. Herein, we describe the case of an elderly male patient who presented with severe chest pain. An initial chest X-ray detected a suspicious lung lesion. Further examination with a positron emission tomography-computed tomography (PET-CT) scan revealed a hypermetabolic mass in the base of the left pleura. A core needle biopsy of the lesion showed features consistent with a benign pleural schwannoma on histopathological assessment. It is crucial for clinicians and radiologists to recognize this unusual presentation to properly diagnose and appropriately treat patients with this type of tumor, as malignant lesions-whether primary or metastatic-are always part of the differential diagnosis in such cases.

Keywords:  benign peripheral nerve sheath tumor; pleural schwannoma; schwannoma

DOI:  https://doi.org/10.25122/jml-2024-0308
Eur J Radiol. 2024 Dec 18. pii: S0720-048X(24)00610-7. [Epub ahead of print]183 111894

Novel MRI signs for differentiating neurogenic and non-neurogenic peripheral nerve Tumors: Insights from Contrast-Enhanced magnetic resonance neurography.

Wenjun Wu, Yuhong Ding, Yu Su, Youzhi Wang, Tingting Liu, Zhiqing Zhang, Dingxi Liu, Chungao Li, Chuansheng Zheng, Lixia Wang.

   OBJECTS: To investigate the specific manifestations of neurogenic and non-neurogenic tumors involving peripheral nerves on contrast-enhanced magnetic resonance neurography (CE-MRN) and explore the potential of CE-MRN in aiding differential diagnosis.
MATERIALS AND METHODS: Twenty-nine patients with neurogenic tumors and 23 with non-neurogenic tumors involving peripheral nerves were enrolled in this study. Both routine MRI and CE-MRN scanning were performed on all subjects. The location, pattern of involvement, classical MRI signs, and novel CE-MRN signs of nerve involvement were evaluated and compared between the two groups. The novel CE-MRN signs included "Enhanced target sign", "Nerve effacing sign", "Nerve wrapping sign", "Nerve compressing sign", "Nerve tail sign", and morphological changes of nerves. Diagnostic confidence in identifying nerve involvement and lesion conspicuity were assessed and compared between routine MRI and CE-MRN.
RESULTS: The majority of neurogenic tumors were schwannoma (79.3 %) and involved a single nerve (75.9 %), whereas the majority of non-neurogenic tumors were malignant tumors (78.3 %) and involved multiple nerves (78.3 %) (P < 0.001). In terms of classical MRI signs, neurogenic tumors exhibited a significantly higher incidence of the "Tail sign" (75.9 % vs 13 %), "Dumbbell sign" (31 % vs 4.3 %), "Target sign" (51.7 % vs 8.7 %), and "Split fat sign" (55.2 % vs 4.3 %), while showing a lower incidence of the "Effacement of fat plane" (3.4 % vs 60.9 %) compared to non-neurogenic tumors (all p < 0.05). Regarding novel CE-MRN signs, neurogenic tumors demonstrated a significantly higher incidence of the "Enhanced target sign" (65.6 % vs 13 %) and the "Nerve tail sign" (100 % vs 13 %), while exhibiting a lower incidence of the "Nerve effacing sign" (0 % vs 52.2 %) and the "Nerve wrapping sign" (0 % vs 17.4 %) compared to non-neurogenic tumors (all p < 0.05). CE-MRN yielded significantly higher diagnostic confidence scores (2.87 ± 0.35 vs 1.75 ± 0.84), but lower lesion conspicuity scores (2.35 ± 0.71 vs 2.92 ± 0.27) compared to routine MRI (all P < 0.001).
CONCLUSION: CE-MRN is a valuable imaging modality for the identification of tumor-related peripheral nerve involvement, as it offers supplementary indicators and enhances diagnostic confidence.

Keywords:  Contrast-enhanced magnetic resonance neurography; Magnetic resonance imaging; Peripheral nerve; Tumor

DOI:  https://doi.org/10.1016/j.ejrad.2024.111894
Trends Neurosci. 2024 Dec 26. pii: S0166-2236(24)00242-X. [Epub ahead of print]

Peripheral, central, and chemotherapy-induced neuropathic changes in pancreatic cancer.

Luju Jiang, Shuqi Cai, Zheqi Weng, Shan Zhang, Shu-Heng Jiang.

  In pancreatic cancer, significant alterations occur in the local nervous system, including axonogenesis, neural remodeling, perineural invasion, and perineural neuritis. Pancreatic cancer can impact the central nervous system (CNS) through cancer cell-intrinsic factors or systemic factors, particularly in the context of cancer cachexia. These peripheral and central neuropathic changes exert substantial influence on cancer initiation and progression. Moreover, chemotherapy-induced neuropathy is common in pancreatic cancer, causing peripheral nerve damage and cognitive dysfunction. Targeting the crosstalk between pancreatic cancer and the nervous system, either peripherally or centrally, holds promise in cancer treatment, pain relief, and improved quality of life. Here, we summarize recent findings on the molecular mechanisms behind these neuropathic changes in pancreatic cancer and discuss potential intervention strategies.

Keywords:  brain–cancer interactions; cancer neuroscience; cognitive impairment; nerve dependence; neural invasion; tumor innervation

DOI:  https://doi.org/10.1016/j.tins.2024.11.008
Abdom Radiol (NY). 2024 Dec 27.

Preoperative clinical and contrasted-enhanced CT features to predict perineural invasion in gallbladder carcinoma: focus on clinical T3-4 stage.

Lu Chen, Yang Zhou, Xun Xu, Hui Zhang, Xuan Xiao, Chang-Xian Li, Wei You, Hai-Bin Shi, Xi-Sheng Liu, Fei-Yun Wu, Xiang-Cheng Li, Fei-Peng Zhu.

   PURPOSE: To investigate the utility of combining clinical and contrasted-enhanced tomography (CECT) parameters for the preoperative evaluation of perineural invasion (PNI) in gallbladder carcinoma (GBC).
METHODS: A total of 134 patients with GBC (male/female, 52/82; age, 64.4 ± 9.7 years) were divided into PNI-positive (n = 63) and PNI-negative groups (n = 71). Clinical characteristics (demographic information, liver function indicators and tumor markers) and CECT parameters (tumor type, tumor size, gallbladder stone, invasion of gallbladder neck/cystic duct, clinical T stage and N stage) were collected and compared between two groups. Binary logistic regression analysis, receiver operating characteristic curves analyses and Delong test were used in further statistical analyses in clinical T3-4 stage (cT3-4) GBC patients. Overall survival (OS) rates after surgery were compared between PNI-negative group and PNI-positive group of cT3-4 GBC patients.
RESULTS: The majority of GBC patients with PNI were classified as cT3-4 (61/63, 96.8%), while only 3.2% (2/63) of PNI-positive cases were identified at cT1-2. Among cT3-4 GBC, OS was significantly lower in the PNI-positive group than the PNI-negative group after surgery (HR,1.661; 95% CI, 1.044-2.643; P = 0.032). Gender and gallbladder neck/cystic duct invasion were independent predictive factors for cT3-4 GBC patients with PNI. A combination of gender and gallbladder neck/cystic duct invasion showed the best diagnostic performance than that of individual parameters (all P < 0.05).
CONCLUSIONS: Preoperative T staging using CECT enables the initial assessment of PNI status in GBC patients. A combination of gender and gallbladder neck/cystic duct invasion may effectively predict PNI in GBC, particularly in cT3-4 GBC.

Keywords:  Clinical T3-4 stage; Contrasted-enhanced CT; Gallbladder carcinoma; Perineural invasion

DOI:  https://doi.org/10.1007/s00261-024-04782-y
Sci Prog. 2024 Oct-Dec;107(4):107(4): 368504241305911

Interventional treatment of right lower lobe bronchial schwannoma under bronchoscopy: A case report and literature review.

Xiyue Li, Ximiao Yu, Ruiqi Luo, Xun Wang.

  Bronchial schwannoma is a rare benign tumor traditionally managed through surgical resection. This case report describes a 69-year-old Chinese woman with an asymptomatic bronchial schwannoma incidentally discovered during routine health check-up. Computed tomography (CT) and bronchoscopy revealed a broad-based mass (27 mm × 16 mm) at the right lower lobe bronchus, causing complete obstruction of the dorsal segment and severe stenosis (>80%) of the basal segment. Histopathological and immunohistochemical analyses confirmed the diagnosis of schwannoma. The patient underwent a single-session multimodal bronchoscopic treatment combining cryotherapy, high-frequency electrocoagulation, and laser therapy, with minimal bleeding (<5 ml). Post-intervention evaluation showed a fully patent right lower lobe bronchus, and at 8-month follow-up, CT confirmed complete resolution without tumor recurrence. This case demonstrates that carefully planned bronchoscopic intervention can effectively manage selected cases of bronchial schwannoma while preserving lung function and minimizing procedural risks.

Keywords:  Bronchial schwannoma; bronchoscope; cryotherapy; electrocoagulation; interventional treatment; laser therapy

DOI:  https://doi.org/10.1177/00368504241305911
Sci Rep. 2024 Dec 28. 14(1): 31096

The diagnosis and treatment of the epithelioid sarcomas involving the peripheral nerves.

Xiaotian Jia, Chaoqun Yang, Lin Chen, Cong Yu, Tadashi Kondo.

  Epithelioid sarcomas are rare soft tissue tumors and have possibility to involve the peripheral nerve and present as sensory and motor disorders. The symptoms are similar to those of nerve compression diseases. This situation is extremely rare in clinic and was only reported as several case reports in literature. It can be easily ignored and misdiagnosed in clinic and may bring out severe outcomes. From January 2003 to December 2017, a retrospective analysis of ten patients with epithelioid sarcomas which involved the peripheral nerves was made. The medical data, detailed clinical courses and the follow-up results were stated. In these cases, the tumors invaded the median nerve, ulnar nerve, radial nerve, brachial plexus, sciatic nerve and presented as relative symptoms. Early diagnosis and treatment are the keys to better prognosis. We recommended high-resolution ultrasound as a standard diagnostic tool for nerve compression syndromes not only reveal the morphological structure of the peripheral nerve, but also discover the tumor involving the nerve. Adequate surgical methods including wide resection and lymph node dissection if necessary. The manners of functional reconstruction need to be applied flexibly by the doctors. Postoperative rehabilitation is important for functional recovery. We want to share our experiences in the diagnosis and treatment to overcome this particular condition.

Keywords:  Epithelioid sarcoma; Functional reconstruction; High-resolution ultrasound; Misdiagnosis; Nerve compression diseases; Peripheral nerve

DOI:  https://doi.org/10.1038/s41598-024-82357-z
Curr Oncol. 2024 Dec 06. 31(12): 7828-7851

Peripheral Neuropathy Instruments for Individuals with Cancer: A COSMIN-Based Systematic Review of Measurement Properties.

Silvia Belloni, Arianna Magon, Chiara Giacon, Francesca Savioni, Gianluca Conte, Rosario Caruso, Cristina Arrigoni.

  Although the literature on patient-reported outcomes (PROMs) continues to expand, challenges persist in selecting reliable and valid instruments for assessing peripheral neuropathy (PN) in patients with cancer. This systematic review aimed to identify all validated self-report PN scales and critically appraise their measurement properties. This review was conducted using the COSMIN methodology for PROMs and the PRISMA statement. Five databases were searched from inception to August 2024, identifying 46 eligible studies and 16 PROMs. Evidence quality ranged from "very low" to "moderate", with notable inconsistencies in the content and structural validity phases of most instruments. Instruments such as the Chemotherapy-induced peripheral neuropathy assessment tool and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity demonstrated moderate quality and potential utility in clinical practice, while others, including the Location-based assessment of sensory symptoms in cancer and the Measure of Ovarian Symptoms and Treatment, had insufficient evidence to support their use. Importantly, all PROMs focused on chemotherapy-induced peripheral neuropathy, highlighting a significant gap in instruments addressing other PN causes, such as radiotherapy or tumor-related nerve damage. Further research should prioritize developing and validating instruments for distinct cancer populations, ensuring robust psychometric properties and clinical applicability.

Keywords:  PROMs; cancer; instruments; patient-reported outcome measure; peripheral neuropathy; reliability; validity

DOI:  https://doi.org/10.3390/curroncol31120577
Cancer Lett. 2024 Dec 18. pii: S0304-3835(24)00800-0. [Epub ahead of print] 217405

N-acetylcysteine prevents cisplatin-induced cognitive impairments in an ovarian cancer rat model.

Naomi Lomeli, Diana C Pearre, Javier Lepe, Donovan A Argueta, Mya A Arellano, Joni L Ricks-Oddie, Kalpna Gupta, Daniela A Bota.

  Cancer-related cognitive impairment (CRCI) is prevalent among cancer patients. A critical disparity in the CRCI field is that most pre-clinical studies have been conducted on young cancer-free male rodents, although CRCI predominantly affects breast cancer and ovarian cancer women survivors. Since oxidative stress is widely implicated in the development of CRCI, we developed an ovarian cancer xenograft rat model of CRCI in Cr:NIH-RNU female rats to examine whether administration of the antioxidant N-acetylcysteine (NAC) prevents cisplatin-induced CRCI without altering its anti-cancer efficacy. In vitro, delayed treatment with NAC (10 h) following cisplatin treatment in the human ovarian cancer cell line SKOV3.ip1 did not decrease cisplatin's anti-cancer efficacy while mitigating hippocampal dendritic branching damage and neuronal apoptosis. Rats received subcutaneous and intraperitoneal implantation of SKOV3.ip1 cells. Rats received one cisplatin (5 mg/kg) injection every two weeks for a total of four cycles, with or without NAC (250 mg/kg/day), given for five consecutive days during cisplatin treatment. NAC was administered 10 hours after cisplatin, based on our in vitro data. Cognitive testing was performed six to seven weeks after treatment cessation. In vivo, cognitive impairments were observed in tumor-bearing rats in the vehicle and cisplatin-treatment groups, while delayed NAC prevented cognitive impairments. Delayed NAC administration did not affect cisplatin-induced tumor volume reduction. Our study supports using NAC to mitigate cisplatin-induced CRCI through the novel development of an ovarian cancer rodent model. This study highlights the importance of developing clinically relevant tumor-bearing models to elucidate the underlying mechanisms associated with CRCI, which will aid in identifying potential therapeutic agents for preventing CRCI.

Keywords:  PSD-95; cancer-related cognitive impairments (CRCI; chemo-brain); cisplatin; glutathione; hippocampal neurons; n-acetylcysteine; neurotoxicity; ovarian cancer

DOI:  https://doi.org/10.1016/j.canlet.2024.217405