bims-netuvo 2024-01-28 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2024–01–28
eight papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Innervation density and types of nerves in prostate cancer.
Influence of Lymphatic, Microvascular and Perineural Invasion on Oncological Outcome in Patients with Neuroendocrine Tumors of the Small Intestine.
Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors.
Hybrid peripheral nerve sheath tumours: MRI features with pathological correlation in 24 cases.
Cancer-mediated axonal guidance of sensory neurons in a microelectrode-based innervation MPS.
Repurposing beta-blockers for combinatory cancer treatment: effects on conventional and immune therapies.
Ancient schwannoma in the right iliac fossa: A case report and review of literature.
Causal effect of beta-blockers on the risk of lung cancer: a Mendelian randomization study.

Neoplasma. 2023 Dec;pii: 231116N593. [Epub ahead of print]70(6): 787-795

Innervation density and types of nerves in prostate cancer.

Filip Blasko, Lucia Krivosikova, Pavel Babal, Jan Breza, Branislav Trebaticky, Roman Kuruc, Boris Mravec, Pavol Janega.

Innervation of cancerous tissue represents an important pathway enabling the nervous system to influence the processes associated with the initiation, progression, and metastasis of a neoplastic process. In the context of prostate cancer, several papers report the presence of innervation and its modulating effect on the cancer prognosis. However, most of the data are experimental, with limited information on human prostate cancer innervation. Morphometric analysis of archival prostate specimen immunohistochemistry with neural markers PGP9.5 and S100 showed a significant decrease of nerve density in the prostate cancer (n=44) compared to the normal prostate tissue (n=18) and benign prostatic hyperplasia (n=28). Sympathetic nerves were detected with TH, parasympathetic with VAChT, and sensory nerves with SP and CGRP protein detection. Dual immunofluorescence revealed numerous sympathetic nerves in normal prostate and benign prostatic hyperplasia, especially in the peripheral parts. Only a few parasympathetic nerves were found between the glands and in the peripheral parts of the prostate and benign hyperplasia. Sporadic positivity for sensory innervation was present only in approximately 1/10 of nerve fibers, especially in the larger nerves. The pattern of innervation in prostate cancer was analogous to that in normal prostate gland and benign prostatic hyperplasia but there was a significantly lower amount of all nerve types, especially in high-grade carcinoma cases. Although not significant, there was a tendency of decreasing innervation density with increasing Gleason score. Regarding the low density of nerves in prostate carcinoma, the significantly lower PCNA counts in nerves of the cancer specimens cannot be ascribed to lower proliferation activity. Our data confirmed the lower nerve density in the prostate cancer compared to the benign prostate tissue. We could not approve an increased nerve proliferation activity in prostate cancer. All nerve types, most the sympathetic, less the parasympathetic, and the sensory nerves, are present in prostate cancer. The highest nerve density at the periphery of the cancer tissue implies this to be the result of an expansive tumor growth. It is evident that the results of experimental prostate cancer models can be applied to human pathology only to a certain extent. The relation between the range of innervation and the biology of prostate cancer is very complex and will require more detailed information to be applied in therapeutic solutions.

DOI: https://doi.org/10.4149/neo_2023_231116N593
Cancers (Basel). 2024 Jan 11. pii: 305. [Epub ahead of print]16(2):

Influence of Lymphatic, Microvascular and Perineural Invasion on Oncological Outcome in Patients with Neuroendocrine Tumors of the Small Intestine.

Frederike Butz, Agata Dukaczewska, Catarina Alisa Kunze, Janina Maren Krömer, Lisa Reinhard, Henning Jann, Uli Fehrenbach, Charlotte Friederieke Müller-Debus, Tatiana Skachko, Johann Pratschke, Peter E Goretzki, Martina T Mogl, Eva Maria Dobrindt.

  For the histopathological work-up of resected neuroendocrine tumors of the small intestine (siNET), the determination of lymphatic (LI), microvascular (VI) and perineural (PnI) invasion is recommended. Their association with poorer prognosis has already been demonstrated in many tumor entities. However, the influence of LI, VI and PnI in siNET has not been sufficiently described yet. A retrospective analysis of all patients treated for siNET at the ENETS Center of Excellence Charité-Universitätsmedizin Berlin, from 2010 to 2020 was performed (n = 510). Patients who did not undergo primary resection or had G3 tumors were excluded. In the entire cohort (n = 161), patients with LI, VI and PnI status had more distant metastases (48.0% vs. 71.4%, p = 0.005; 47.1% vs. 84.4%, p < 0.001; 34.2% vs. 84.7%, p < 0.001) and had lower rates of curative surgery (58.0% vs. 21.0%, p < 0.001; 48.3% vs. 16.7%, p < 0.001; 68.4% vs. 14.3%, p < 0.001). Progression-free survival was significantly reduced in patients with LI, VI or PnI compared to patients without. This was also demonstrated in patients who underwent curative surgery. Lymphatic, vascular and perineural invasion were associated with disease progression and recurrence in patients with siNET, and these should therefore be included in postoperative treatment considerations.

Keywords:  lymphatic invasion; microvascular invasion; oncological outcome; perineural invasion; small-intestinal neuroendocrine tumors

DOI:  https://doi.org/10.3390/cancers16020305
Cancer Sci. 2024 Jan 26.

Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors.

Haruyoshi Katayama, Atsushi Fujimura, Rongsheng Huang, Yusuke Otani, Takuto Itano, Tomohiro Fujiwara, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki.

  Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through β2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST.

Keywords:  Schwann cell; benserazide; cancer stem cell; catecholamine synthase; malignant peripheral nerve sheath tumor; vesicular monoamine transporter

DOI:  https://doi.org/10.1111/cas.16077
Br J Radiol. 2024 Jan 23. 97(1153): 126-134

Hybrid peripheral nerve sheath tumours: MRI features with pathological correlation in 24 cases.

Saurabh Singh, Paul Choong, Mohamed Ali, Daniel Lindsay, Asif Saifuddin.

   OBJECTIVES: To describe the MRI features of histologically proven hybrid peripheral nerve sheath tumours (HPNST).
METHODS: A retrospective analysis of the MRI features of 24 histologically proven cases of HPNST over 7 years. Demographic data obtained from clinical records included age, gender, and date of diagnosis. Two readers independently assessed MRI studies and assessed the following features: involvement of a major nerve, intramuscular location, lesion morphology, entering nerve sign, exiting nerve sign, target sign, fascicular sign, split fat sign, and ancient change (cystic change). Inter-observer agreement was assessed with Cohen's kappa coefficient. Histological diagnosis was based on either image-guided needle biopsy or resection histology.
RESULTS: The study included 9 males and 15 females with mean age 50 years (range: 24-78 years). Nine tumours (35%) involved a major nerve including spinal roots (5), radial (1), median (1), tibial (1), and axillary (1), while 5 (21%) tumours were intramuscular. The mean tumour size was 4.2 cm (standard deviation of 2.4 cm). The frequency of MRI features was as follows: lobular contour (71%; 17/24), ancient change (38%; 9/24), fascicular sign (17%; 4/24), entering nerve sign (21%; 5/24), exiting nerve sign (13%; 3/24), target sign (13%; 3/24), and split fat sign (8%; 2/24). Inter-observer agreement was high, ranging from 0.7 to 0.83.
CONCLUSIONS: HPNST infrequently demonstrate the classical MRI signs of benign peripheral nerve sheath tumours, but commonly have a lobular morphology and can show ancient/cystic change.
ADVANCES IN KNOWLEDGE: This is the first study in the literature analysing the MRI features of histologically proven HPNST. HPNST infrequently shows the classical MRI signs that would be expected with benign peripheral nerve sheath tumours although commonly have a lobular morphology and show cystic change.

Keywords:  hybrid nerve sheath tumour; magnetic resonance imaging; nerve sheath neoplasms; neurilemmoma; neurofibroma; perineurioma; schwannoma

DOI:  https://doi.org/10.1093/bjr/tqad001
Biofabrication. 2024 Jan 23.

Cancer-mediated axonal guidance of sensory neurons in a microelectrode-based innervation MPS.

Matthijs van der Moolen, Andrea Lovera, Fulya Ersoy, Sacha Mommo, Peter Loskill, Paolo Cesare.

  Despite recent advances in the field of microphysiological systems (MPS), availability of models capable of mimicking the interactions between the nervous system and innervated tissues is still limited. This represents a significant challenge in identifying the underlying processes of various pathological conditions, including neuropathic, cardiovascular and metabolic disorders. In this study, we introduce a compartmentalized 3D coculture system that enables physiologically relevant tissue innervation while recording neuronal excitability. By integrating custom microelectrode arrays into tailored glass chips microfabricated via selective laser-etching, we developed an entirely novel class of innervation MPSs (INV-MPS). This INV-MPS allows for manipulation, visualization, and electrophysiological analysis of individual axons innervating complex 3D tissues. Here, we focused on sensory innervation of 3D tumor tissue as a model case study since cancer-induced pain represents a major unmet medical need. The system was compared with existing nociception models and successfully replicated axonal chemoattraction mediated by nerve growth factor (NGF). Remarkably, in the absence of NGF, 3D cancer spheroids cocultured in the adjacent compartment induced sensory neurons to consistently cross the separating barrier and establish fine innervation. Moreover, we observed that crossing sensory fibers could be chemically excited by distal application of known pain-inducing agonists only when cocultured with cancer cells. To our knowledge, this is the first system showcasing morphological and electrophysiological analysis of 3D-innervated tumor tissue in vitro, paving the way for a plethora of studies into innervation-related diseases and improving our understanding of underlying pathophysiology.

Keywords:  Cancer; Dorsal root ganglia; Microelectrode array; Microphysiological System; Pain

DOI:  https://doi.org/10.1088/1758-5090/ad218a
Front Pharmacol. 2023 ;14 1325050

Repurposing beta-blockers for combinatory cancer treatment: effects on conventional and immune therapies.

Rachel Massalee, Xuefang Cao.

  Beta-adrenergic receptor signaling regulates cellular processes associated with facilitating tumor cell proliferation and dampening anti-tumor immune response. These cellular processes may lead to compromised tumor control and cancer progression. Based on this ramification, Beta-blockers (BBs) have emerged as a potential treatment by inhibiting beta-adrenergic receptor signaling. This review aimed to investigate the relationship between the use of BBs and tumor progression and treatment response. Therefore, the authors explored several aspects: the potential synergistic relationship of BBs with chemotherapy and immunotherapy in enhancing the effectiveness of chemotherapeutic and immunotherapeutic treatments and their role in boosting endogenous immunity. Further, this review explores the distinctions between the major types of BBs: Non-selective Beta Blockers (NSBBs) and Selective Beta Blockers (SBBs), and their contributions to combinatory cancer treatment. In this review, we presented a perspective interpretation of research findings and future directions. Overall, this review discusses the potential and challenge that BBs present in improving the effectiveness and outcome of cancer treatment.

Keywords:  beta blockers; chemotherapy; immunotherapy; non selective beta blockers; selective beta blocker

DOI:  https://doi.org/10.3389/fphar.2023.1325050
Radiol Case Rep. 2024 Mar;19(3): 1195-1199

Ancient schwannoma in the right iliac fossa: A case report and review of literature.

Marwan Alaswad, Tariq Saleh, Fatima Alaidaros, Abdullah Al Otry, Ayman Z Azzam, Tarek M Amin.

  Ancient schwannomas are a rare variation of schwannomas, with the distinction being based on histopathological examination of the excised specimen. On histopathological examination, ancient schwannomas exhibit degenerative changes such as calcification, hyalinization, and cystic necrosis, along with S100 positivity. Complete surgical excision is the mainstay treatment for ancient schwannomas and carries a favorable prognosis. Recurrence is the most common complication, often arising from incomplete surgical excision. Herein, we present a case of a 41-year-old male who presented to our center as a case of a retroperitoneal mass for further investigations and diagnostic workup. Imaging showed a retroperitoneal mass in the right iliac fossa. We proceeded with ultrasound guided needle biopsy, and examination of the specimen confirmed the diagnosis of ancient schwannoma. Subsequently, the patient underwent surgery, and complete surgical excision was achieved. On follow-up 3-months later, the patient is doing well, and no signs of recurrence were found.

Keywords:  Ancient schwannoma; Iliac fossa; Retroperitoneal

DOI:  https://doi.org/10.1016/j.radcr.2023.12.028
J Thorac Dis. 2023 Dec 30. 15(12): 6651-6660

Causal effect of beta-blockers on the risk of lung cancer: a Mendelian randomization study.

Yi Lu, Jiachun Luo, Zhenyu Huo, Fan Ge, Yang Chen, Ying Chen, Qing Zhang, Caichen Li, Jinhui Wang, Jiayu Gan, Ziqiu Cheng, Yangbin Li, Yi Feng, Qiyuan Hu, Jianxing He, Wenhua Liang.

   Background: It remains uncertain whether there is a causal association of the use of beta-blockers (BBs) on lung cancer risk. We used a two-sample Mendelian randomization (MR) approach to identify the causal association of BBs and lung cancer risk.
Methods: Twenty-two BB-related single-nucleotide polymorphisms (SNPs) were obtained from the UK Biobank as the instrumental variables (IVs). Genetic summary data information of lung cancer was extracted from the International Lung Cancer Consortium, with a total of 11,348 cases and 15,861 controls. We adopted the inverse-variance weighted (IVW) approach to conduct the MR analyses. Egger-intercept analysis was further performed as sensitivity analysis for pleiotropy evaluation. Additionally, we investigated whether BBs could causally affect the risk of lung cancer through their pharmacological effects.
Results: The current IVW analysis suggested a decreased lung cancer risk in BB users [odds ratio (OR) =0.83; 95% confidence interval (CI): 0.73-0.95; P<0.01]. Results of Egger-intercept analysis demonstrated that no pleiotropy was found (P=0.94), which suggested the robustness of the causality. However, there was little evidence that pharmacological effects mediate the association between BBs and lung cancer.
Conclusions: The current analysis suggested that BBs could decrease the risk of lung cancer but may be not via its pharmacological effects. Further research is in need for elucidating the underlying mechanisms.

Keywords:  Mendelian randomization (MR); beta-blockers (BBs); lung cancer; risk factors

DOI:  https://doi.org/10.21037/jtd-23-1098