bims-netuvo 2024-04-28 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2024–04–28
ten papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Adrenergic microenvironment driven by cancer-associated Schwann cells contributes to chemoresistance in patients with lung cancer.
Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy.
A Novel In Vitro Pathological Model for Studying Neural Invasion in Non-Melanoma Skin Cancer.
Peripheral Nerve Sheath Tumor: A Diagnostic and Therapeutic Challenge.
Expression of Calcitonin Gene-Related Peptide and Calcitonin Receptor-like Receptor in Colorectal Adenocarcinoma.
Concomitant treatment of ureteral calculi and ipsilateral pelvic sciatic nerve schwannoma with transperitoneal laparoscopic approach: A case report.
Malignant transformation of vestibular schwannoma after radiation therapy.
Decorin suppresses stemness and migration potential of malignant peripheral nerve sheath tumor through inhibiting epidermal growth factor receptor signaling.
Rare retroperitoneal giant sacral schwannoma: A case report.
A light in the darkness: sodium fluorescein-assisted peripheral nerve sheath tumors resection - a comprehensive systematic review and single-arm meta-analysis.

Cancer Sci. 2024 Apr 27.

Adrenergic microenvironment driven by cancer-associated Schwann cells contributes to chemoresistance in patients with lung cancer.

Yusuke Otani, Haruyoshi Katayama, Yidan Zhu, Rongsheng Huang, Takafumi Shigehira, Kazuhiko Shien, Ken Suzawa, Hiromasa Yamamoto, Tadahiko Shien, Shinichi Toyooka, Atsushi Fujimura.

  Doublecortin (DCX)-positive neural progenitor-like cells are purported components of the cancer microenvironment. The number of DCX-positive cells in tissues reportedly correlates with cancer progression; however, little is known about the mechanism by which these cells affect cancer progression. Here we demonstrated that DCX-positive cells, which are found in all major histological subtypes of lung cancer, are cancer-associated Schwann cells (CAS) and contribute to the chemoresistance of lung cancer cells by establishing an adrenergic microenvironment. Mechanistically, the activation of the Hippo transducer YAP/TAZ was involved in the acquisition of new traits of CAS and DCX positivity. We further revealed that CAS express catecholamine-synthesizing enzymes and synthesize adrenaline, which potentiates the chemoresistance of lung cancer cells through the activation of YAP/TAZ. Our findings shed light on CAS, which drive the formation of an adrenergic microenvironment by the reciprocal regulation of YAP/TAZ in lung cancer tissues.

Keywords:  YAP/TAZ; adrenaline; cancer‐associated Schwann cells; doublecortin; microenvironment

DOI:  https://doi.org/10.1111/cas.16164
Front Mol Neurosci. 2024 ;17 1345811

Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy.

Xinyu Chen, Yumeng Gan, Ngan Pan Bennett Au, Chi Him Eddie Ma.

  Chemotherapy-induced peripheral neuropathy (CIPN) is the most common off-target adverse effects caused by various chemotherapeutic agents, such as cisplatin, oxaliplatin, paclitaxel, vincristine and bortezomib. CIPN is characterized by a substantial loss of primary afferent sensory axonal fibers leading to sensory disturbances in patients. An estimated of 19-85% of patients developed CIPN during the course of chemotherapy. The lack of preventive measures and limited treatment options often require a dose reduction or even early termination of life-saving chemotherapy, impacting treatment efficacy and patient survival. In this Review, we summarized the current understanding on the pathogenesis of CIPN. One prominent change induced by chemotherapeutic agents involves the disruption of neuronal cytoskeletal architecture and axonal transport dynamics largely influenced by the interference of microtubule stability in peripheral neurons. Due to an ineffective blood-nerve barrier in our peripheral nervous system, exposure to some chemotherapeutic agents causes mitochondrial swelling in peripheral nerves, which lead to the opening of mitochondrial permeability transition pore and cytochrome c release resulting in degeneration of primary afferent sensory fibers. The exacerbated nociceptive signaling and pain transmission in CIPN patients is often linked the increased neuronal excitability largely due to the elevated expression of various ion channels in the dorsal root ganglion neurons. Another important contributing factor of CIPN is the neuroinflammation caused by an increased infiltration of immune cells and production of inflammatory cytokines. In the central nervous system, chemotherapeutic agents also induce neuronal hyperexcitability in the spinal dorsal horn and anterior cingulate cortex leading to the development of central sensitization that causes CIPN. Emerging evidence suggests that the change in the composition and diversity of gut microbiota (dysbiosis) could have direct impact on the development and progression of CIPN. Collectively, all these aspects contribute to the pathogenesis of CIPN. Recent advances in RNA-sequencing offer solid platform for in silico drug screening which enable the identification of novel therapeutic agents or repurpose existing drugs to alleviate CIPN, holding immense promises for enhancing the quality of life for cancer patients who undergo chemotherapy and improve their overall treatment outcomes.

Keywords:  chemotherapy-induced peripheral neuropathy; cold allodynia; dorsal root ganglion; intraepidermal nerve fibers; mechanical allodynia

DOI:  https://doi.org/10.3389/fnmol.2024.1345811
Gels. 2024 Apr 08. pii: 252. [Epub ahead of print]10(4):

A Novel In Vitro Pathological Model for Studying Neural Invasion in Non-Melanoma Skin Cancer.

Paula Ávila-Fernández, Miguel Etayo-Escanilla, David Sánchez-Porras, Cristina Blanco-Elices, Fernando Campos, Víctor Carriel, Óscar Darío García-García, Jesús Chato-Astrain.

  Neural Invasion (NI) is a key pathological feature of cancer in the colonization of distant tissues, and its underlying biological mechanisms are still scarcely known. The complex interactions between nerve and tumor cells, along with the stroma, make it difficult to reproduce this pathology in effective study models, which in turn has limited the understanding of NI pathogenesis. In this study, we have designed a three-dimensional model of NI squamous cell carcinoma combining human epidermoid carcinoma cells (hECCs) with a complete peripheral nerve segment encapsulated in a fibrine-agarose hydrogel. We recreated two vital processes of NI: a pre-invasive NI model in which hECCs were seeded on the top of the nerve-enriched stroma, and an invasive NI model in which cancer cells were immersed with the nerve in the hydrogel. Histological, histochemical and immunohistochemical analyses were performed to validate the model. Results showed that the integration of fibrin-agarose advanced hydrogel with a complete nerve structure and hECCs successfully generated an environment in which tumor cells and nerve components coexisted. Moreover, this model correctly preserved components of the neural extracellular matrix as well as allowing the proliferation and migration of cells embedded in hydrogel. All these results suggest the suitability of the model for the study of the mechanisms underlaying NI.

Keywords:  advanced hydrogel models; cancer neural invasion; head and neck squamous cell carcinoma; tissue engineering

DOI:  https://doi.org/10.3390/gels10040252
Cureus. 2024 Mar;16(3): e56601

Peripheral Nerve Sheath Tumor: A Diagnostic and Therapeutic Challenge.

Deviprasad Sulli, Chandni Shankar, Shruti G Raikar.

   INTRODUCTION: Peripheral nerve tumors are a group of rare soft tissue tumors of neuro-ectodermal origin. Although the majority of them are benign in nature, up to 10% can be malignant. The symptoms depend on the site, size, and structures compressed by the tumor.
AIM: To highlight the heterogeneity of signs and symptoms and their presentations, which has often made it difficult for the attending physician to accurately diagnose and direct the patient toward appropriate treatment.
METHODS: Eight patients treated at our tertiary care hospital between 2015 and 2022 were included in this study. They were evaluated in detail. Treatment was surgical. The patients underwent complete excision of the tumor under magnification to help preserve the adjacent neurovascular bundle. All patients were followed up post-operatively to document the status of their symptoms.
RESULTS: The average duration prior to referral to our hospital was 13 months. Seven subjects had pain at presentation, one had neurological deficit. Seven also complained of swelling. Five of the eight lesions were schwannoma, two neurofibroma and one showed malignant histology. Post-operatively, Hoffman Tinel signs improved in all six subjects. five of the seven subjects were completely pain-free, and the other two had a reduction in symptoms.
CONCLUSIONS: Early diagnosis and referral to a specialist center are needed to achieve satisfactory outcomes while treating peripheral nerve tumors. Proliferative lesions should be treated surgically in specialist centers by experienced doctors with appropriate skills and equipment for microsurgical procedures to ensure full recovery.

Keywords:  hoffman tinel sign; neurilemmoma; neurofibroma; peripheral nerve sheath tumors; schwannoma

DOI:  https://doi.org/10.7759/cureus.56601
Int J Mol Sci. 2024 Apr 18. pii: 4461. [Epub ahead of print]25(8):

Expression of Calcitonin Gene-Related Peptide and Calcitonin Receptor-like Receptor in Colorectal Adenocarcinoma.

Robert-Emmanuel Șerban, Mioara-Desdemona Stepan, Dan Nicolae Florescu, Mihail-Virgil Boldeanu, Mirela-Marinela Florescu, Mircea-Sebastian Șerbănescu, Mihaela Ionescu, Liliana Streba, Nicoleta-Alice-Marinela Drăgoescu, Pavel Christopher, Vasile-Cosmin Obleagă, Cristian Constantin, Cristin Constantin Vere.

  Colorectal cancer is one of the most widespread types of cancer that still causes many deaths worldwide. The development of new diagnostic and prognostic markers, as well as new therapeutic methods, is necessary. The calcitonin gene-related peptide (CGRP) neuropeptide alongside its receptor calcitonin receptor-like receptor (CRLR) could represent future biomarkers and a potential therapeutic target. Increased levels of CGRP have been demonstrated in thyroid, prostate, lung, and breast cancers and may also have a role in colorectal cancer. At the tumor level, it acts through different mechanisms, such as the angiogenesis, migration, and proliferation of tumor cells. The aim of this study was to measure the level of CGRP in colorectal cancer patients' serum by enzyme-linked immunosorbent assay (ELISA) and determine the level of CGRP and CRLR at the tumor level after histopathological (HP) and immunohistochemical (IHC) analysis, and then to correlate them with the TNM stage and with different tumoral characteristics. A total of 54 patients with newly diagnosed colorectal adenocarcinoma were evaluated. We showed that serum levels of CGRP, as well as CGRP and CRLR tumor level expression, correlate with the TNM stage, with local tumor extension, the presence of lymph node metastasis, and distant metastasis, and also with the tumor differentiation degree. CGRP is present in colorectal cancer from the incipient TNM stage, with levels increasing with the stage, and can be used as a diagnostic and prognostic marker and may also represent a potentially new therapeutic target.

Keywords:  calcitonin gene-related peptide; calcitonin receptor-like receptor; colorectal adenocarcinoma

DOI:  https://doi.org/10.3390/ijms25084461
World J Clin Cases. 2024 Apr 16. 12(11): 1947-1953

Concomitant treatment of ureteral calculi and ipsilateral pelvic sciatic nerve schwannoma with transperitoneal laparoscopic approach: A case report.

Yang Xiong, Jin Li, Han-Jie Yang.

   BACKGROUND: Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells. Of the different types of schwannomas, pelvic sciatic nerve schwannoma is extremely rare. Definite preoperative diagnosis of pelvic schwannomas is difficult, and surgical resection is the gold standard for its definite diagnosis and treatment.
CASE SUMMARY: We present a case of pelvic schwannoma arising from the sciatic nerve that was detected in a 40-year-old man who underwent computed tomography for intermittent right lower back pain caused exclusively by a right ureteral calculus. Subsequently, successful transperitoneal laparoscopic surgery was performed for the intact removal of the stone and en bloc resection of the schwannoma. The total operative time was 125 min, and the estimated blood loss was inconspicuous. The surgical procedure was uneventful. The patient was discharged on postoperative day 5 with the simultaneous removal of the urinary catheter. However, the patient presented with motor and sensory disorders of the right lower limb, caused by partial damage to the right sciatic nerve. No tumor recurrence was observed at the postoperative appointment.
CONCLUSION: Histopathological examination of the specimen confirmed the diagnosis of a schwannoma. Thus, laparoscopic surgery is safe and feasible for concomitant extirpation of pelvic schwannomas and other pelvic and abdominal diseases that require surgical treatment.

Keywords:  Case report; Laparoscopy; Pelvic neoplasms; Schwannoma; Sciatic nerve; Ureteral calculi

DOI:  https://doi.org/10.12998/wjcc.v12.i11.1947
Radiol Case Rep. 2024 Jul;19(7): 2654-2662

Malignant transformation of vestibular schwannoma after radiation therapy.

Anastasia Drakos, Augusto Goncalves Filho, John Woulfe, Paulo Puac Polanco, Eduardo Portela de Oliveira.

  Stereotactic radiosurgery (SRS) is an effective treatment for vestibular schwannomas, offering high rates of tumor control and low neurological risks. Long-term complications of SRS are not fully understood, with several cases of malignant transformation reported in the literature. We report the case of a 50-year-old female with no prior history of neurofibromatosis who presented in 2013 with MRI evidence of a benign vestibular schwannoma. Despite treatment with CyberKnife SRS, she presented 6 years later with new onset neurologic symptoms. Further investigation showed stable lesion size with increasing vasogenic edema and a new area of enhancement in the brainstem, suspicious for malignant transformation. Subsequent treatment with partial craniectomy and histopathologic analysis was consistent with a malignant peripheral nerve sheath tumor diagnosis. Our case adds to a series of 24 similar cases in the literature, details of which have been summarized in our study. Overall, findings support the need for lifelong surveillance following SRS treatment of benign vestibular schwannomas. Patients should be educated on the potential risk of this complication, and clinicians must maintain a high level of suspicion for potential radiation-induced malignancy during the patient's clinical course.

Keywords:  CyberKnife; Gamma Knife; Malignant peripheral nerve sheath tumor; Stereotactic radiosurgery; Vestibular schwannoma

DOI:  https://doi.org/10.1016/j.radcr.2024.03.033
Biochim Biophys Acta Mol Basis Dis. 2024 Apr 21. pii: S0925-4439(24)00170-4. [Epub ahead of print] 167181

Decorin suppresses stemness and migration potential of malignant peripheral nerve sheath tumor through inhibiting epidermal growth factor receptor signaling.

Xiaotian Jia, Lin Chen, Cong Yu.

  Cancer stem cells (CSCs) play pivotal roles in the growth, invasion, metastasis, chemo-resistance in malignant peripheral nerve sheath tumor (MPNST). The current characterization of CSCs in MPNST is not complete. Decorin is a critical regulator of microenvironment, but its expression and function in CSCs of MPNST has not been studied. In the current study, Decorin levels and its relationship with lung and liver metastasis were determined in clinical specimens. Decorin expression in CD133-positive or CD44-positive CSCs was analyzed by RT-qPCR on cytospun MPNST cells after flow cytometry-based cell sorting. Decorin-positive cells were separated from Decorin-negative cells in transfected MPNST cell lines using a designed plasmid expressing red fluorescent protein (RFP) under a Decorin promoter. Tumor sphere formation, tumor growth, cell invasion, cell migration, and the resistance to chemotherapy-induced apoptosis were determined on Decorin-positive versus Decorin-negative MPNST cells. In vivo tumor growth was analyzed in mice receiving subcutaneous transplantation of Decorin-positive versus Decorin-negative MPNSTs. We found that Decorin levels were significantly downregulated in MPNST specimens, compared to non-tumorous adjacent tissue. Significantly lower Decorin levels were detected in MPNSTs with lung or liver metastasis compared to those without. Poorer patient survival was detected in Decorin-low MPNST, compared to Decorin-high subjects. More Decorin-negative cells were detected in CD133-positive MPNST cells than CD133-negative MPNST cells, and in CD44-positive MPNST cells than in CD44-negative MPNST cells. Compared to Decorin-positive MPNST cells, Decorin-negative MPNST cells generated significantly more tumor spheres in culture, were more invasive and migratory, and were more resistant to chemotherapy-induced apoptosis, likely due to the inhibition of epidermal growth factor receptor signaling by Decorin. Decorin-negative MPNST cells grew significantly larger tumor in vivo. Thus, depletion of Decorin may occur in CSCs in MPNSTs, serving possibly as a new therapeutic target.

Keywords:  Cancer metastasis; Cancer stem cells (CSCs); Decorin; Malignant peripheral nerve sheath tumor (MPNST); Stemness

DOI:  https://doi.org/10.1016/j.bbadis.2024.167181
Oncol Lett. 2024 Jun;27(6): 261

Rare retroperitoneal giant sacral schwannoma: A case report.

Shunchang Zhou, Shenyi Wan, Liang Li, Wei Dong, Xuhui Ma, Haibo Chu, Yuxu Zhong.

  Schwannomas localized in the sacrum are relatively infrequent, accounting for 1-5% of all spinal axis schwannomas; they present with vague symptoms or are symptomless, so often grow to a considerable size before detection. Sacral schwannomas occasionally present with enormous dimensions, and these tumors are termed giant sacral schwannomas. However, their surgical removal is challenging owing to an abundant vascularity. The present study retrospectively analyzed the clinical and follow-up data of a patient with a giant sacral schwannoma. The patient experienced numbness in the left buttock and lower extremity, with radiating pain in the sole of the foot that had persisted for 3 years. A presacral mass was found by computed tomography examination 6 months after the stool had become thin. A tumor resection was performed using the anterior abdominal approach. A schwannoma was diagnosed by postoperative pathology. The postoperative course was uneventful, with the complete resolution of symptoms during the 21-month clinical follow-up. Overall, the present study reports the case of a giant sacral schwannoma with pelvic pain that was resected without complications and also discusses its successful management. Additionally, the study presents a systematic review of the literature. We consider that the surgical treatment of giant sacral schwannomas with piecemeal subtotal excision can achieve good outcomes, avoiding unnecessary neurological deficits.

Keywords:  operation; pre-sacral; sacral schwannoma

DOI:  https://doi.org/10.3892/ol.2024.14394
Neurosurg Rev. 2024 Apr 23. 47(1): 181

A light in the darkness: sodium fluorescein-assisted peripheral nerve sheath tumors resection - a comprehensive systematic review and single-arm meta-analysis.

Gabriel Verly, Thiffany Delfino, Leonardo de Barros Oliveira, Sávio Batista, Marcelo Porto Sousa, Rodrigo Schevz, Marcio Yuri Ferreira, Raphael Bertani.

  The treatment for peripheral nerve sheath tumors (PNSTs) is based on surgical excision and the primary goal is to improve symptoms whilst preserving neurological function. In order to improve this technique, surgeons may use sodium fluorescein (SF) to help visualize the neoplasm and, consequently, facilitate its removal. Aiming to assess the efficacy of this emerging surgical strategy, we conducted a systematic review and single-arm meta-analysis. We conducted a systematic search on the PubMed, Embase, and Web of Science databases, following the PRISMA guidelines. Studies without outcomes of interest, case series with less than four patients, letters, comments, technical notes, editorials, reviews, and basic research papers were excluded. The outcomes considered for this study were: the number of tumors that achieved total resection, subtotal resection, or near total resection, the approach/technique utilized by the surgeon, SF-related complications, and total complications. Five studies, with a total of 175 individuals, were included in our survey. Notably, 70% of the neoplasms presented by the patients were schwannomas. Considering extracranial lesions, we found a proportion of 96% (95% CI: 88 - 100%) in total resection, 0% (95% CI: 0-1%) in near total resection, and 4% (95% CI: 0-12%) in subtotal resection, all linked to an amount of 185 analyzed PNSTs. Furthermore, a proportion of 1% (95% CI: 0 - 2%) in SF-related complications was spotted among 183 patients. Finally, total complications analysis accounted for 11% (95% CI: 0 - 25%) among 183 individuals. We concluded that SF-assisted resection of PNSTs is a suitable and relatively safe technique, linked to minimum complications, of which the majority was not associated with the chemical compound itself. Future research is necessary to increase the number of patients available in the current literature and, therefore, enhance future analyses.

Keywords:  Fluorescein; Neurosurgery; Peripheral nerve; Resection; Schwannoma; Tumor

DOI:  https://doi.org/10.1007/s10143-024-02414-z