bims-netuvo 2024-11-03 papers

Issue of 2024‒11‒03
six papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Biomedicines. 2024 Oct 14. pii: 2335. [Epub ahead of print]12(10):

Remarks on Selected Morphological Aspects of Cancer Neuroscience: A Microscopic Photo Review.

Ewa Iżycka-Świeszewska, Jacek Gulczyński, Aleksandra Sejda, Joanna Kitlińska, Susana Galli, Wojciech Rogowski, Dawid Sigorski.

BACKGROUND: This short review and pictorial essay presents a morphological insight into cancer neuroscience, which is a complex and dynamic area of the pathobiology of tumors.METHODS: We discuss the different methods and issues connected with structural research on tumor innervation, interactions between neoplastic cells and the nervous system, and dysregulated neural influence on cancer phenotypes.
RESULTS: Perineural invasion (PNI), the most-visible cancer-nerve relation, is briefly presented, focusing on its pathophysiology and structural diversity as well as its clinical significance. The morphological approach to cancer neurobiology further includes the analysis of neural density/axonogenesis, neural network topographic distribution, and composition of fiber types and size. Next, the diverse range of neurotransmitters and neuropeptides and the neuroendocrine differentiation of cancer cells are reviewed. Another morphological area of cancer neuroscience is spatial or quantitative neural-related marker expression analysis through different detection, description, and visualization methods, also on experimental animal or cellular models.
CONCLUSIONS: Morphological studies with systematic methodologies provide a necessary insight into the structure and function of the multifaceted tumor neural microenvironment and in context of possible new therapeutic neural-based oncological solutions.

Keywords: axonogenesis; cancer neuroscience; nerve density; nerve pathology; neural factors; neurotransmitters; perineural invasion

DOI: https://doi.org/10.3390/biomedicines12102335

CNS Neurosci Ther. 2024 Oct;30(10): e70097

Neural Influences on Tumor Progression Within the Central Nervous System.

Wenhao Lv, Yongjie Wang.

For decades, researchers have studied how brain tumors, the immune system, and drugs interact. With the advances in cancer neuroscience, which centers on defining and therapeutically targeting nervous system-cancer interactions, both within the local tumor microenvironment (TME) and on a systemic level, the subtle relationship between neurons and tumors in the central nervous system (CNS) has been deeply studied. Neurons, as the executors of brain functional activities, have been shown to significantly influence the emergence and development of brain tumors, including both primary and metastatic tumors. They engage with tumor cells via chemical or electrical synapses, directly regulating tumors or via intricate coupling networks, and also contribute to the TME through paracrine signaling, secreting proteins that exert regulatory effects. For instance, in a study involving a mouse model of glioblastoma, the authors observed a 42% increase in tumor volume when neuronal activity was stimulated, compared to controls (p < 0.01), indicating a direct correlation between neural activity and tumor growth. These thought-provoking results offer promising new strategies for brain tumor therapies, highlighting the potential of neuronal modulation to curb tumor progression. Future strategies may focus on developing drugs to inhibit or neutralize proteins and other bioactive substances secreted by neurons, break synaptic connections and interactions between infiltrating cells and tumor cells, as well as disrupt electrical coupling within glioma cell networks. By harnessing the insights gained from this research, we aspire to usher in a new era of brain tumor therapies that are both more potent and precise.

Keywords: central nervous system tumors; neuron; oligodendrocyte precursor cell; paracrine signal; synapse

DOI: https://doi.org/10.1111/cns.70097

Sci Rep. 2024 Oct 31. 14(1): 26235

TSPO deficiency promotes the progression of malignant peripheral sheath tumors by regulating the G2/M phase of the cell cycle via CDK1.

Xingnan Zhang, Chenhao Hu, Shengqiao Sun, Chao Guo, Yakun Bu, Zicong Wang, Zewei Liu, Xiaoli Zhang, Dezhi Li, Song Liu.

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell-derived sarcomas that are sporadic or associated with Neurofibromatosis 1 (NF1) gene mutations. Traditional therapies are usually ineffective for treating MPNSTs, so new targets need to be identified for the treatment of MPNSTs. In the present study, the role of the mitochondrial translocator protein (TSPO) in the regulation of cell proliferation and the cell cycle in MPNSTs was investigated. TSPO expression was lower in MPNSTs than in NFs. Loss-of-function experiments revealed that TSPO deficiency promoted MPNST cell growth, migration, and invasion and influenced the cell cycle in vitro and in vivo. In addition, TSPO depletion suppressed cell apoptosis by downregulating the expression of caspase-3, caspase-8, HSP60, p27, p53, and BCL-2 and suppressed the cell cycle by upregulating CDK1, CDK2, CCNB1 and CCNA2. Furthermore, CDK1 was determined to be an upstream target of TSPO-mediated regulation via RNA-seq, qPCR, and Western blotting. Specifically, depletion of CDK1 weakened the effect of TSPO deficiency on cell proliferation and migration. More importantly, CDK1 knockdown induced significant cell cycle arrest in the G2/M phase. In summary, TSPO deficiency regulates the cell cycle in MPNSTs by targeting CDK1, which may be an effective molecular target for prognosis evaluation and treatment.

Keywords: CDK1; Cell cycle; Malignant peripheral nerve sheath tumors (MPNSTs); TSPO

DOI: https://doi.org/10.1038/s41598-024-77933-2

Cancers (Basel). 2024 Oct 12. pii: 3463. [Epub ahead of print]16(20):

Influence of Perineural (Pn), Lymphangio (L) and Vascular (V) Invasion on Survival after Resection of Perihilar Cholangiocarcinoma.

Rabea Margies, Lisa-Katharina Gröger, Beate K Straub, Fabian Bartsch, Hauke Lang.

INTRODUCTION: Perihilar cholangiocarcinoma is a rare malignancy of the biliary tract, for which surgery remains the treatment of choice. However, even after radical resection, the prognosis is poor. In addition to tumor size, depth of invasion and nodal/metastatic status, the TNM classification includes additional parameters such as perineural (Pn), lymphangio (L) and vascular (V) invasion. The prognostic impact of these factors is not yet fully understood. The aim of this study was to investigate the influence of these parameters on overall survival after resection of perihilar cholangiocarcinoma.MATERIAL AND METHODS: Data from all patients who underwent surgical exploration for perihilar cholangiocarcinoma between January 2013 and December 2023 were included into an institutional database. The impact of perineural, lymphangio and vascular invasion on overall survival was analyzed.
RESULTS: Over the 11-year period, a total of 214 patients underwent surgical exploration for perihilar cholangiocarcinoma. Curative intended resection was possible in 168 patients (78.5%). Perineural invasion, lymphangio invasion and vascular invasion were present in 79.2%, in 17.3% and in 14.3% of patients, respectively. Cross tabulation revealed a significant association between the presence of L1 and V1 (p = 0.006). There was also a significant association of Pn1, L1, and V1 with R-status (p = 0.010; p = 0.006 and p ≤ 0.001). While V1 was associated with significantly worse overall survival across the entire cohort, Pn1 alone showed only a tendency towards worse overall survival without reaching statistical significance. In Bismuth type IV, both L1 and V1, but not Pn1, were significantly associated with worse overall survival (p = 0.001; p = 0.017 and p = 0.065).
CONCLUSIONS: Perineural invasion is very common in perihilar cholangiocarcinoma. Although Pn1 was associated with a tendency toward worse survival, it did not reach statistical significance. In contrast, vascular invasion significantly worsened overall survival in the entire cohort, and lymphangio invasion was linked to worse overall survival in Bismuth type IV tumors. The combination of perineural invasion with positivity of more than one additional factor (either L or V) was also associated with worse overall survival. In patients with Bismuth type IV, these pathological markers appeared to have even greater prognostic relevance.

Keywords: liver surgery; lymphangio invasion; overall survival; perihilar cholangiocarcinoma; perineural invasion; vascular invasion

DOI: https://doi.org/10.3390/cancers16203463

J Theor Biol. 2024 Oct 23. pii: S0022-5193(24)00252-2. [Epub ahead of print]595 111967

A continuous approach of modeling tumorigenesis and axons regulation for the pancreatic cancer.

Marie-Jose Chaaya, Sophie Chauvet, Florence Hubert, Fanny Mann, Mathieu Mezache, Pierre Pudlo.

The pancreatic innervation undergoes dynamic remodeling during the development of pancreatic ductal adenocarcinoma (PDAC). Denervation experiments have shown that different types of axons can exert either pro- or anti-tumor effects, but conflicting results exist in the literature, leaving the overall influence of the nervous system on PDAC incompletely understood. To address this gap, we propose a continuous mathematical model of nerve-tumor interactions that allows in silico simulation of denervation at different phases of tumor development. This model takes into account the pro- or anti-tumor properties of different types of axons (sympathetic or sensory) and their distinct remodeling dynamics during PDAC development. We observe a "shift effect" where an initial pro-tumor effect of sympathetic axon denervation is later outweighed by the anti-tumor effect of sensory axon denervation, leading to a transition from an overall protective to a deleterious role of the nervous system on PDAC tumorigenesis. Our model also highlights the importance of the impact of sympathetic axon remodeling dynamics on tumor progression. These findings may guide strategies targeting the nervous system to improve PDAC treatment.

Keywords: Cancer; Dynamical system; In silico denervation; Parameter calibration; Partial differential equations

DOI: https://doi.org/10.1016/j.jtbi.2024.111967

Anesth Analg. 2024 Oct 04.

Anesthetic Techniques and Cancer Outcomes: What Is the Current Evidence?

Mohd S Ramly, Donal J Buggy.

It is almost 2 decades since it was first hypothesized that anesthesia technique might modulate cancer biology and thus potentially influence patients' long-term outcomes after cancer surgery. Since then, research efforts have been directed towards elucidating the potential pharmacological and physiological basis for the effects of anesthetic and perioperative interventions on cancer cell biology. In this review, we summarize current laboratory and clinical data. Taken together, preclinical studies suggest some biologic plausibility that cancer cell function could be influenced. However, available clinical evidence suggests a neutral effect. Observational studies examining cancer outcomes after surgery of curative intent for many cancer types under a variety of anesthetic techniques have reported conflicting results, but warranting prospective randomized clinical trials (RCTs). Given the large patient numbers and long follow-up times required for adequate power, relatively few such RCTs have been completed to date. With the sole exception of peritumoral lidocaine infiltration in breast cancer surgery, these RCTs have indicated a neutral effect of anesthetic technique on long-term oncologic outcomes. Therefore, unless there are significant new findings from a few ongoing trials, future investigation of how perioperative agents interact with tumor genes that influence metastatic potential may be justified. In addition, building multidisciplinary collaboration to optimize perioperative care of cancer patients will be important.

DOI: https://doi.org/10.1213/ANE.0000000000007183