bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2024–04–14
eleven papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute
  1. Peripheral cancer remodeling of central neural system.
  2. The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer.
  3. Pharmacogenomic synthetic lethal screens reveal hidden vulnerabilities and new therapeutic approaches for treatment of NF1-associated tumors.
  4. Conditionally replicative adenovirus as a therapy for malignant peripheral nerve sheath tumors.
  5. Case report: Solitary mass of the sciatic nerve confirmed as a primary extranodal manifestation of diffuse large B-cell lymphoma in a geriatric patient.
  6. [Penile cancer with perineural invasion is more prone to postoperative recurrence].
  7. Double role of depression in gastric cancer: As a causative factor and as consequence.
  8. Robot-assisted minimally invasive bronchial resection with primary anastomosis for schwannoma arising from left main bronchus: a case report.
  9. Do beta-blockers reduce negative intrusive thoughts and anxiety in cancer survivors? - An emulated trial.
  10. Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases.
  11. Using Nerve Blocks for Addressing Radiation-Induced Pain During Pelvic Cancer Treatment.
  1. Cell Res. 2024 Apr 12.
    Peripheral cancer remodeling of central neural system.
    Gray Umbach, Shawn L Hervey-Jumper.
      
    DOI:  https://doi.org/10.1038/s41422-024-00960-1
  2. BMC Cancer. 2024 Apr 08. 24(1): 433
    The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer.
    Hao Chen, Chao Wang, Zexian Chen, Tianze Huang, Yanyun Lin, Junguo Chen, Bin Zhang, Xiaosheng He.
       BACKGROUND: Perineural invasion (PNI) is the invasion of nerves by cancer cells and is associated with poor survival in stage II colorectal cancer. However, PNI can be further subdivided according to the depth of invasion, and the depth of PNI has not been clearly linked to prognosis.
    METHOD: This study aimed to assess the prognostic value of different depths of PNI in stage II colorectal cancer. We defined PNI in the submucosal plexus and myenteric plexus as superficial perineural invasion (sup-PNI) and PNI in the subserous plexus as deep perineural invasion (deep-PNI). Patients were divided into three groups based on the depth of PNI: sup-PNI, deep-PNI and non-PNI. Then, univariate and multivariate Cox regression analyses were conducted to evaluate the role of PNI in the prognosis of stage II colorectal cancer.
    RESULTS: This study enrolled 3508 patients with stage II colorectal cancer who underwent resection for primary colorectal lesions between January 2013 and September 2019. Clinicopathological features, including elevated carcinoembryonic antigen (CEA) levels, T4 stage, poor differentiation, deficient DNA mismatch repair (dMMR), and vascular invasion, were correlated with deep-PNI. Multivariate analyses revealed that deep-PNI was associated with worse overall survival (OS; hazard ratio [HR], 3.546; 95% confidence interval [CI], 2.307-5.449; P < 0.001) and disease-free survival (DFS; HR, 2.921; 95% CI, 2.032-4.198; P < 0.001), compared with non-PNI. Conversely, no significant difference in OS or DFS was observed between the sup-PNI and non-PNI groups in multivariate analyses.
    CONCLUSIONS: The study demonstrated that the depth of PNI was an independent prognostic factor for patients with stage II colorectal cancer, and patients with deep PNI had a worse prognosis. Thus, patients with PNI require further subdivision according to the depth of invasion.
    Keywords:  Colorectal cancer; Perineural invasion; Survival
    DOI:  https://doi.org/10.1186/s12885-024-12206-9
  3. bioRxiv. 2024 Mar 25. pii: 2024.03.25.585959. [Epub ahead of print]
    Pharmacogenomic synthetic lethal screens reveal hidden vulnerabilities and new therapeutic approaches for treatment of NF1-associated tumors.
    Kyle B Williams, Alex T Larsson, Bryant J Keller, Katherine E Chaney, Rory L Williams, Minu M Bhunia, Garrett M Draper, Tyler A Jubenville, Sue K Rathe, Christopher L Moertel, Nancy Ratner, David A Largaespada.
      Neurofibromatosis Type 1 (NF1) is a common cancer predisposition syndrome, caused by heterozygous loss of function mutations in the tumor suppressor gene NF1 . Individuals with NF1 develop benign tumors of the peripheral nervous system (neurofibromas), originating from the Schwann cell linage after somatic loss of the wild type NF1 allele, some of which progress further to malignant peripheral nerve sheath tumors (MPNST). There is only one FDA approved targeted therapy for symptomatic plexiform neurofibromas and none approved for MPNST. The genetic basis of NF1 syndrome makes associated tumors ideal for using synthetic drug sensitivity approaches to uncover therapeutic vulnerabilities. We developed a drug discovery pipeline to identify therapeutics for NF1-related tumors using isogeneic pairs of NF1- proficient and deficient immortalized human Schwann cells. We utilized these in a large-scale high throughput screen (HTS) for drugs that preferentially kill NF1 -deficient cells, through which we identified 23 compounds capable of killing NF1- deficient Schwann cells with selectivity. Multiple hits from this screen clustered into classes defined by method of action. Four clinically interesting drugs from these classes were tested in vivo using both a genetically engineered mouse model of high-grade peripheral nerve sheath tumors and human MPNST xenografts. All drugs tested showed single agent efficacy in these models as well as significant synergy when used in combination with the MEK inhibitor selumetinib. This HTS platform yielded novel therapeutically relevant compounds for the treatment of NF1-associated tumors and can serve as a tool to rapidly evaluate new compounds and combinations in the future.
    DOI:  https://doi.org/10.1101/2024.03.25.585959
  4. Mol Ther Oncol. 2024 Jun 20. 32(2): 200783
    Conditionally replicative adenovirus as a therapy for malignant peripheral nerve sheath tumors.
    Julia A Nikrad, Robert T Galvin, Mackenzie M Sheehy, Ethan L Novacek, Kari L Jacobsen, Stanislas M A S Corbière, Pauline J Beckmann, Tyler A Jubenville, Masato Yamamoto, David A Largaespada.
      Oncolytic adenoviruses (Ads) stand out as a promising strategy for the targeted infection and lysis of tumor cells, with well-established clinical utility across various malignancies. This study delves into the therapeutic potential of oncolytic Ads in the context of neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNSTs). Specifically, we evaluate conditionally replicative adenoviruses (CRAds) driven by the cyclooxygenase 2 (COX2) promoter, as selective agents against MPNSTs, demonstrating their preferential targeting of MPNST cells compared with non-malignant Schwann cell control. COX2-driven CRAds, particularly those with modified fiber-knobs exhibit superior binding affinity toward MPNST cells and demonstrate efficient and preferential replication and lysis of MPNST cells, with minimal impact on non-malignant control cells. In vivo experiments involving intratumoral CRAd injections in immunocompromised mice with human MPNST xenografts significantly extend survival and reduce tumor growth rate compared with controls. Moreover, in immunocompetent mouse models with MPNST-like allografts, CRAd injections induce a robust infiltration of CD8+ T cells into the tumor microenvironment (TME), indicating the potential to promote a pro-inflammatory response. These findings underscore oncolytic Ads as promising, selective, and minimally toxic agents for MPNST therapy, warranting further exploration.
    Keywords:  MT: Regular Issue; conditionally replicative adenovirus (CRAd); cyclooxygenase 2 (COX2); malignant peripheral nerve sheath tumor (MPNST); neurofibromatosis type 1 (NF1); oncolytic adenovirus
    DOI:  https://doi.org/10.1016/j.omton.2024.200783
  5. Front Oncol. 2024 ;14 1354073
    Case report: Solitary mass of the sciatic nerve confirmed as a primary extranodal manifestation of diffuse large B-cell lymphoma in a geriatric patient.
    Hannes Becker, Antonio Vogelsberg, Daniel Feucht, Arne Estler, Deniz Tafrali, Jens Schittenhelm, Jakob Milla, Sylvia Kurz, Falko Fend, Marcos Tatagiba, Martin U Schuhmann, Helene Hurth.
       Background: Neoplastic lesions affecting peripheral nerves are rare in the general population and, most often, are benign peripheral nerve sheath tumors. However, a minority of lesions represent high-grade malignancies associated with a poor prognosis, such as malignant peripheral nerve sheath tumors (MPNSTs). Very rarely, these tumors represent peripheral non-nerve sheath tumors (PNNSTs), such as hematological neoplasms that impair nerve function. These can be hard to distinguish from MPNSTs and other lesions arising from the nerve itself. In the present case report, we describe a rare case of direct infiltration of nerves by tumor cells of a hematological neoplasm.
    Methods: We report the case of a 90-year-old woman with acute onset of right-sided foot palsy, sensory loss, and pain, caused by an extensive solitary mass of the sciatic nerve in the thigh. We present and discuss the clinical presentation, multimodal diagnostic procedures, and treatment.
    Results: MRI of the right thigh and the caudal pelvis revealed a contrast-enhancing lesion infiltrating the sciatic nerve. Additionally performed staging imaging was non-revealing. After multidisciplinary discussion in the neuro-oncology tumor board, a MPNST was suspected and the patient underwent radical tumor resection. However, final histopathology revealed a diffuse large B-cell lymphoma (DLBCL). The patient received adjuvant palliative local radiotherapy which led to acceptable symptom control.
    Conclusion: Rare PNNSTs, including extranodal manifestations of DLBCL can have similar clinical and radiological diagnostical features as PNSTs. Comprehensive diagnostic workup of contrast-enhancing lesions affecting peripheral nerves including MRI and metabolic imaging are recommended. Discussion in interdisciplinary tumor boards facilitates finding individual treatment approaches.
    Keywords:  B-cell lymphoma; extranodal manifestation; peripheral nerves; peripheral non nerve sheath tumor; sciatic nerve
    DOI:  https://doi.org/10.3389/fonc.2024.1354073
  6. Zhonghua Nan Ke Xue. 2023 Apr;29(4): 337-341
    [Penile cancer with perineural invasion is more prone to postoperative recurrence].
    Yue-Fu Han, Xin-Hua Yao, Ji-Wang Deng, Bin Lai, Yong-Mao Zeng, Lian Peng, Zi-Jian Tang, Chen Wang, Jun-Wei Li.
       OBJECTIVE: To explore the correlation between perineural invasion and postoperative recurrence in patients surgically treated for penile cancer.
    METHODS: We conducted a retrospective analysis of the clinical data on 18 penile cancer patients surgically treated in our hospital from January 2018 to December 2021, 8 with postoperative recurrence (the recurrence group) and the other 10 without (the non-recurrence control group). We compared the two groups of patients in the age of onset, tumor-node-metastasis (TNM) stages, American Joint Committee on Cancer (AJCC) prognosis stages, surgical methods, perineural invasion and recurrence time. We analyzed the differences in postoperative recurrence using the Kaplan Meier plotted survival curve and in independent risk factors in predicting postoperative recurrence using the ROC curve.
    RESULTS: Compared with the non-recurrence controls, the patients in the recurrence group had a significantly older age of onset (P=0.0411) and severer perineural invasion (P<0.001), and those with perineural invasion had a shorter recurrence time (P<0.001), which was an independent risk factor for postoperative recurrence. The areas under the ROC curves for perineural invasion and age were 0.885 and 0.213, respectively.
    CONCLUSION: Penile cancer with perineural invasion is more prone to and perineural invasion is an independent risk factor for postoperative recurrence of the malignancy.
    Keywords:   penile cancer; perineural invasion; partial penile resection; radical penile resection; recurrence
  7. World J Gastroenterol. 2024 Mar 14. 30(10): 1266-1269
    Double role of depression in gastric cancer: As a causative factor and as consequence.
    Grigorios Christodoulidis, Koumarelas Konstantinos-Eleftherios, Kouliou Marina-Nektaria.
      In this editorial we comment on the article "Hotspots and frontiers of the relationship between gastric cancer and depression: A bibliometric study". Gastric cancer (GC) is a common malignancy in the digestive system with increased mortality and morbidity rates globally. Standard treatments, such as gastrectomy, negatively impact patients' quality of life and beyond the physical strain, GC patients face psychological challenges, including anxiety and depression. The prevalence of depression can be as high as 57%, among gastrointestinal cancer patients. Due to the advancements in treatment effectiveness and increased 5-year overall survival rates, attention has shifted to managing psychological effects. However, the significance of managing the depression doesn't lie solely in the need for a better psychological status. Depression leads to chronic stress activating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, leading release of catecholamines inducing tumor proliferation, migration, and metastasis, contributing to GC progression. The dysregulation of neurotransmitters and the involvement of various signaling pathways underscore the complex interplay between depression and GC. Comprehensive strategies are required to address the psychological aspects of GC, including region-specific interventions and increased monitoring for depression. Understanding the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex disease. In this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.
    Keywords:  Anxiety; Chronic stress; Depression; Gastric cancer; Pathogenesis of gastric cancer
    DOI:  https://doi.org/10.3748/wjg.v30.i10.1266
  8. Transl Lung Cancer Res. 2024 Mar 29. 13(3): 654-665
    Robot-assisted minimally invasive bronchial resection with primary anastomosis for schwannoma arising from left main bronchus: a case report.
    Yan Yan, Runsen Jin, Xiaoyan Chen, Yajie Zhang, Hecheng Li.
       Background: Tracheobronchial schwannomas are extremely rare, which account for lower than 0.2% in all pulmonary tumors. In large part because of the rarity and insufficient reported clinical details, tracheobronchial schwannoma lacks guidelines or expert consensus for diagnosis and treatment, and the delay in diagnosis can range from months to years. The main treatment option is surgery. Endoscopic intervention can also be selected. An increasing number of thoracic surgery cases were performed on the robotic platforms in recent years. With their assistance, surgeons can accomplish the high technique required surgical procedures with ease.
    Case Description: In this case, a 48-year-old female had a history of shortness of breath for more than 1 year. The chest computed tomography (CT) and bronchoscopy examination revealed a new growth of nodule in the left main bronchus. The nodule was considered a schwannoma by transbronchial biopsy, which was removed by robot-assisted bronchial resection with primary anastomosis. The application of Da Vinci Si robotic surgical system benefited the process of this surgery. Pathology and immunohistochemistry results confirmed the diagnosis of schwannomas. The patient tolerated the treatment without any complications. No sign of recurrence was discovered at present, 6 months after the intervention.
    Conclusions: We reported the first sleeve resection for bronchial schwannoma using Da Vinci robotic surgical system. The clinical details of tracheobronchial schwannoma should be revealed more specifically to achieve more systematic diagnosis and treatment.
    Keywords:  Schwannomas; case report; primary tracheobronchial tumor; robot-assisted surgery
    DOI:  https://doi.org/10.21037/tlcr-23-819
  9. BMC Cancer. 2024 Apr 11. 24(1): 447
    Do beta-blockers reduce negative intrusive thoughts and anxiety in cancer survivors? - An emulated trial.
    Carolina Ehrencrona, Ying Li, Eva Angenete, Eva Haglind, Stefan Franzén, Anna Grimby-Ekman, David Bock.
       BACKGROUND: High rates of negative intrusive thoughts have been reported among cancer patients. Prevalent users of beta-blocker therapy have reported lower levels of cancer related intrusive thoughts than non-user. The aim of this study is to investigate if initiation of beta-blocker therapy reduces the prevalence and severity of intrusive thoughts (co-primary endpoints) and the prevalence of anxiety, depressed mood, and low quality of life (secondary endpoints) in cancer survivors.
    METHODS: Data on patient-reported outcomes from three cohort studies of Swedish patients diagnosed with colon, prostate or rectal cancer were combined with data on beta-blocker prescriptions retrieved from the Swedish Prescribed Drug Register. Two randomized controlled trials were emulated. Trial 1 had follow-up 1 year after diagnosis, trial 2 had follow-up 2 years after diagnosis, baseline in both trials was 12 months before follow-up. Those who initiated beta-blocker therapy between baseline and follow-up was assigned Active group, those who did not was assigned Control group. All endpoints were analysed using Bayesian ordered logistic regression.
    RESULTS: Trial 1 consisted of Active group, n = 59, and Control group, n = 3936. Trial 2 consisted of Active group, n = 87, and Control group, n = 3132. The majority of participants were men, 83% in trial 1 and 94% in trial 2. The prevalence and severity of intrusive thoughts were lower in the Active group in trial 1, but no significant differences between groups were found in either trial. The prevalence of depressed mood, worse quality of life and periods of anxiety were higher in the Active group in both trials with significant differences for quality of life in trial 1 and anxiety in trial 2.
    CONCLUSIONS: The emulated trials demonstrated no evidence of a protective effect of beta-blocker therapy against intrusive thoughts. The Active group had reduced quality of life and elevated anxiety compared to the Control group.
    TRIAL REGISTRATION: The three cohort studies were registered at isrctn.com/clinicaltrials.gov (ISRCTN06393679, NCT02530593 and NCT01477229).
    Keywords:  Adrenergic beta-antagonists; Cancer survivors; Colorectal cancer; Intrusive thoughts; Prostate cancer; Psychological Distress; Quality of life; Trial emulation
    DOI:  https://doi.org/10.1186/s12885-024-12236-3
  10. J Nanobiotechnology. 2024 Apr 08. 22(1): 159
    Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases.
    Jun Jiang, Yuan Lu, Jie Chu, Xiao Zhang, Chao Xu, Shaojie Liu, Zhuo Wan, Jiawei Wang, Lu Zhang, Kui Liu, Zhenhua Liu, Angang Yang, Xinling Ren, Rui Zhang.
      Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM.
    Keywords:  Blood-brain barrier; Brain metastasis; Drug delivery; Engineered exosomes; Lung cancer
    DOI:  https://doi.org/10.1186/s12951-024-02414-7
  11. JAMA Oncol. 2024 Apr 11.
    Using Nerve Blocks for Addressing Radiation-Induced Pain During Pelvic Cancer Treatment.
    Jolinta Y Lin, Jill S Remick, Vinita Singh.
      
    DOI:  https://doi.org/10.1001/jamaoncol.2024.0304
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