bims-netuvo 2022-11-13 papers

Issue of 2022‒11‒13
seven papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

Cancers (Basel). 2022 Oct 26. pii: 5246. [Epub ahead of print]14(21):

Neural Component of the Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma.

Michał Gola, Aleksandra Sejda, Janusz Godlewski, Małgorzata Cieślak, Anna Starzyńska.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive primary malignancy of the pancreas, with a dismal prognosis and limited treatment options. It possesses a unique tumor microenvironment (TME), generating dense stroma with complex elements cross-talking with each other to promote tumor growth and progression. Diversified neural components makes for not having a full understanding of their influence on its aggressive behavior. The aim of the study was to summarize and integrate the role of nerves in the pancreatic tumor microenvironment. The role of autonomic nerve fibers on PDAC development has been recently studied, which resulted in considering the targeting of sympathetic and parasympathetic pathways as a novel treatment opportunity. Perineural invasion (PNI) is commonly found in PDAC. As the severity of the PNI correlates with a poorer prognosis, new quantification of this phenomenon, distinguishing between perineural and endoneural invasion, could feature in routine pathological examination. The concepts of cancer-related neurogenesis and axonogenesis in PDAC are understudied; so, further research in this field may be warranted. A better understanding of the interdependence between the neural component and cancer cells in the PDAC microenvironment could bring new nerve-oriented treatment options into clinical practice and improve outcomes in patients with pancreatic cancer. In this review, we aim to summarize and integrate the current state of knowledge and future challenges concerning nerve-cancer interactions in PDAC.

Keywords: pancreatic ductal adenocarcinoma; perineural invasion; tumor innervation; tumor microenvironment

DOI: https://doi.org/10.3390/cancers14215246

Brain Sci. 2022 Nov 02. pii: 1486. [Epub ahead of print]12(11):

The Rostral Ventromedial and Lateral Medulla Are the Major Areas Responsive to Lung Cancer Progression among Brainstem Lung-Innervating Nuclei.

Mo Chen, Yingfu Jiao, Yumiao Shi, Saihong Xu, Dan Tang, Sihan Chen, Po Gao, Xindi Zhang, Xiaojing Zhao, Mengmeng Cai, Weifeng Yu, Kangjie Xie.

In recent years, the information crosstalk between the central nervous system and the periphery has been a hot topic, such as the brain-gut axis, brain-lung axis, etc. Among them, some studies have shown that brainstem nuclei activity can significantly affect the progression of peripheral tumor; however, regarding lung cancer, our understanding of the basic characteristics of the lung-innervating brain nuclei responsive to lung cancer progression remains deficient. Therefore, we used the pseudorabies virus for retrograde labeling of nerves to study the neural circuits between the lung and brain. We then established a mouse orthotopic lung cancer model and used the expression of the c-Fos gene in brain regions to characterize activated brain circuits and compared these results with those of the control group. We focused on c-Fos activity in nuclei associated with retrograde tracing regions of the brainstem. We found over 16 nuclei in the whole brain with direct or indirect lung innervation through neural retrograde labeling with the pseudorabies virus. We further revealed that the neuronal activity of the rostral ventrolateral reticular nucleus (RVL), caudal nucleus of Raphe (raphe obscurus nucleus, ROb), Raphe pallidus nucleus (RPa), and ventral gigantocellular reticular nucleus (GiV) in the rostral ventromedial and lateral medulla were significantly changed in an orthotopic lung cancer mouse model by the immunostaining of c-Fos early responsive protein. Thus, the distinctive rostroventral medulla area, functionally closely related to the vagus nerve, likely plays a role in central neural interaction with peripheral lung tumors and deserves future investigation.

Keywords: brainstem nuclei; brain–lung axis; c-Fos; crosstalk; lung cancer; neural circuit; pseudorabies virus; retrograde tracing; vagal core

DOI: https://doi.org/10.3390/brainsci12111486

AJR Am J Roentgenol. 2022 Nov 09.

Association of CT Findings With Perineural Invasion in Gallbladder Cancer: Preliminary Assessment.

Yashi Marodia, Jyoti Kharel, Uma Nahar, Rajender Kumar, Thakur Deen Yadav, Vikas Gupta, Lileshwar Kaman, Chandan Das, Usha Dutta, Pankaj Gupta.

Perineural invasion (PNI) indicates a worse prognosis in patients with gallbladder cancer (GBC). This preliminary retrospective study included 19 patients with GBC who underwent contrast-enhanced CT within 4 weeks before surgical resection. The GBC showed PNI on pathologic assessment in 8/19 patients. On CT, wall-thickening morphology had sensitivity of 75.0% and specificity of 81.8% for PNI; soft tissue stranding around the celiac plexus had sensitivity of 62.5% and specificity of 100.0% for PNI.

DOI: https://doi.org/10.2214/AJR.22.28580

Prog Mol Biol Transl Sci. 2022 ;pii: S1877-1173(22)00064-3. [Epub ahead of print]193(1): 37-63

Adrenergic receptors in breast cancer.

Cecilia Pérez Piñero, Ezequiel Mariano Rivero, Lucía Gargiulo, María Sol Rodríguez, Carlos David Bruque, Ariana Bruzzone, Isabel Alicia Lüthy.

Breast cancer is the most diagnosed malignancy in women worldwide and in the majority of the countries. Breast cancers are classified on the expression of estrogen and progesterone receptor expression and overexpression of human epidermal growth factor receptor 2 (HER2) as luminal, HER2+ and triple negative breast cancer. The intrinsic molecular subtypes match this classification. Cancer diagnosis and treatment cause distress. In both acute and chronic stress, the secreted catecholamines adrenaline and noradrenaline trigger the "fight-or-flight" response. This chapter focuses on the actions of the β2 and α2 adrenergic receptors in several models of breast cancer. The actions of these receptors depend on the model used to investigate them. The β2-adrenergic receptors seem to exert a dual action. They can directly act on the epithelial cells inhibiting cell proliferation and migration/invasion and indirectly upon the immune microenvironment. The proportion of β2 receptors in each compartment could, therefore, lean the scale to an inhibition or to an exacerbation of tumor growth, invasion and metastasis. All the work points to a beneficial or neutral action of β-blockers on breast cancer. With respect to α2-adrenergic receptors, the investigation performed by our group suggest that the α2B and the α2C receptors are linked to enhanced cell proliferation and tumor growth acting through both the epithelial and the stromal (fibroblastic) compartments while α2A could be beneficial for patients. Some adrenergic compounds could be repurposed for breast cancer treatment due to their very low side effects and very well-known pharmacology.

Keywords: Adrenergic receptors; Bioinformatics; Breast cancer; Experimental; Human

DOI: https://doi.org/10.1016/bs.pmbts.2022.06.002

Cancer Discov. 2022 Nov 11. OF1

Nociceptor Neurons Affect Immunosurveillance and Tumor Growth.

Tumor-innervating nociceptor neurons promote CD8+ T-cell exhaustion and tumor growth.

DOI: https://doi.org/10.1158/2159-8290.CD-RW2022-198

Biochem Biophys Res Commun. 2022 Dec 10. pii: S0006-291X(22)01259-1. [Epub ahead of print]633 20-22

Rethinking the visceral innervation --- Peek into the emerging field of molecular dissection of neural signals.

Xulin Li, Liping Wang.

Communication between the nervous system and the viscera, comprising the afferent and efferent pathways, is a fundamental part of maintaining homeostasis. The cellular and molecular properties of the visceral innervation have long been obscure. Emerging techniques applied in neuroscience including single-cell RNA sequencing approaches prove us with powerful tools to tackle the unsolved puzzles. This perspective aims to derive and inspire new insights into the integrative roles of the nervous system based on the latest research progress.

DOI: https://doi.org/10.1016/j.bbrc.2022.09.011

Surg Today. 2022 Nov 11.

A refined prediction of early recurrence combining tumor deposits in patients with resected rectal mucinous adenocarcinoma.

Yanwu Sun, Yu Deng, Meifang Xu, Jingming Zhong, Jianyuan Song, Huiming Lin, Weizhong Jiang, Ying Huang, Pan Chi.

PURPOSE: Early recurrence (ER) of rectal mucinous adenocarcinoma (MAC) has yet to be defined. We therefore explored risk factors for ER and constructed a predictive nomogram.METHOD: A total of 145 rectal MAC patients undergoing radical surgery were included. The minimum P value method was used to determine the optimal cut-off point to discriminate between ER and late recurrence (LR). Risk factors for ER were determined by a logistic regression analysis, and a predictive nomogram was constructed.
RESULTS: A total of 62 (42.8%) patients developed tumor recurrence. The optimal time to define ER was 12 months. A pre-treatment tumor distance from the anal verge ≤ 7 cm, pathological N stage, lymphovascular invasion, tumor deposits, and time to recurrence ≤ 12 months were significantly associated with a poor post-recurrence survival in patients with recurrence. A pre-treatment serum carcinoembryonic antigen (CEA) level > 10 ng/ml, pre-treatment tumor distance from the anal verge ≤ 7 cm, pathological N + stage, perineural invasion, and tumor deposits were identified as independent risk factors associated with ER. A nomogram predicting ER was constructed (C-index 0.870).
CONCLUSION: The pre-treatment serum CEA level, pre-treatment tumor distance from the anal verge, pathological N + stage, perineural invasion, and tumor deposits were significantly predictive of ER for rectal MAC patients.

Keywords: Early recurrence; Mucinous adenocarcinoma; Nomogram; Rectal cancer

DOI: https://doi.org/10.1007/s00595-022-02613-5