bims-netuvo 2023-11-26 papers

Issue of 2023‒11‒26
six papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Dig Liver Dis. 2023 Nov 18. pii: S1590-8658(23)01004-6. [Epub ahead of print]

Analysis of exposome and genetic variability suggests stress as a major contributor for development of pancreatic ductal adenocarcinoma.

Giulia Peduzzi, Alessio Felici, Roberto Pellungrini, Francesca Giorgolo, Riccardo Farinella, Manuel Gentiluomo, Andrea Spinelli, Gabriele Capurso, Anna Monreale, Federico Canzian, Marco Calderisi, Daniele Campa.

BACKGROUND: The current knowledge on pancreatic ductal adenocarcinoma (PDAC) risk factors is limited and no study has comprehensively tested the exposome in combination with the genetic variability in relation to the disease susceptibility.AIM: The aim of this study was to analyze the exposome and its interaction with known genetic susceptibility loci, in relation to PDAC risk.
METHODS: A case-control study nested in UK Biobank cohort was conducted on 816 PDAC cases and 302,645 controls. A total of 347 exposure variables, and a polygenic risk score (PRS) were analyzed through logistic regression. Gene-environment interaction analyses were conducted.
RESULTS: A total of 52 associations under the Bonferroni corrected threshold of p < 1.46 × 10-4 were observed. Known risk factors such as smoking, pancreatitis, diabetes, PRS, heavy alcohol drinking and overweight were replicated in this study. As for novel associations, a clear indication for length and intensity of mobile phone use and the stress-related factors and stressful events with increase of PDAC risk was observed. Although the PRS was associated with PDAC risk (P = 2.09 × 10-9), statistically significant gene-exposome interactions were not identified.
CONCLUSION: In conclusion, our results suggest that a stressful lifestyle and sedentary behaviors may play a major role in PDAC susceptibility independently from the genetic background.

Keywords: Cancer; Gene-environment interaction; Polygenic risk score; SNPs; UK Biobank

DOI: https://doi.org/10.1016/j.dld.2023.10.015

Handb Exp Pharmacol. 2023 Nov 21.

β-Adrenoceptors in Cancer: Old Players and New Perspectives.

Rosario Amato, Martina Lucchesi, Silvia Marracci, Luca Filippi, Massimo Dal Monte.

Distress, or negative stress, is known to considerably increase the incidence of several diseases, including cancer. There is indeed evidence from pre-clinical models that distress causes a catecholaminergic overdrive that, mainly through the activation of β-adrenoceptors (β-ARs), results in cancer cell growth and cancer progression. In addition, clinical studies have evidenced a role of negative stress in cancer progression. Moreover, plenty of data demonstrates that β-blockers have positive effects in reducing the pro-tumorigenic activity of catecholamines, correlating with better outcomes in some type of cancers as evidenced by several clinical trials. Among β-ARs, β2-AR seems to be the main β-AR subtype involved in tumor development and progression. However, there are data indicating that also β1-AR and β3-AR may be involved in certain tumors. In this chapter, we will review current knowledge on the role of the three β-AR isoforms in carcinogenesis as well as in cancer growth and progression, with particular emphasis on recent studies that are opening new avenues in the use of β-ARs as therapeutic targets in treating tumors.

Keywords: Cancer cell proliferation; Carcinogenesis; Catecholamines; Dedifferentiation; Immune-tolerance; Stress; Tumor growth; Tumor infiltration; Tumor microenvironment

DOI: https://doi.org/10.1007/164_2023_701

Biology (Basel). 2023 Nov 11. pii: 1418. [Epub ahead of print]12(11):

Acetylcholine, Another Factor in Breast Cancer.

Juan P Muñoz, Gloria M Calaf.

Acetylcholine (ACh) is a neurotransmitter that regulates multiple functions in the nervous system, and emerging evidence indicates that it could play a role in cancer progression. However, this function is controversial. Previously, we showed that organophosphorus pesticides decreased the levels of the enzyme acetylcholinesterase in vivo, increasing ACh serum levels and the formation of tumors in the mammary glands of rats. Furthermore, we showed that ACh exposure in breast cancer cell lines induced overexpression of estrogen receptor alpha (ERα), a key protein described as the master regulator in breast cancer. Therefore, here, we hypothesize that ACh alters the ERα activity through a ligand-independent mechanism. The results here reveal that the physiological concentration of ACh leads to the release of Ca+2 and the activity of MAPK/ERK and PI3K/Akt pathways. These changes are associated with an induction of p-ERα and its recruitment to the nucleus. However, ACh fails to induce overexpression of estrogen-responsive genes, suggesting a different activation mechanism than that of 17ß-estradiol. Finally, ACh promotes the viability of breast cancer cell lines in an ERα-dependent manner and induces the overexpression of some EMT markers. In summary, our results show that ACh promotes breast cancer cell proliferation and ERα activity, possibly in a ligand-independent manner, suggesting its putative role in breast cancer progression.

Keywords: acetylcholine; breast cancer; estrogen receptor alpha; estrogens; muscarinic receptor

DOI: https://doi.org/10.3390/biology12111418

J Breast Cancer. 2023 Nov 17.

Nipple Schwannoma: A Case Report and Literature Review on Nipple Mass.

Ye Ju Kang, Ok Hee Woo, Aeree Kim.

Schwannomas are slow-growing benign tumors originating from the Schwann cells of the peripheral nerve sheaths. Herein, we report the first documented case of a schwannoma presenting as a painful nipple mass in a 32-year-old woman. This mass initially developed six years ago following a period of breastfeeding. Breast magnetic resonance imaging (MRI) scans revealed an iso-intense mass, with an approximate size of 2.2 cm, on a T1-weighted image (T1WI) with internal cystic changes. The mass exhibited heterogeneously delayed enhancement and restricted diffusion. Surgical excision was performed, and the diagnosis of cutaneous plexiform nipple schwannoma was confirmed histopathologically. A literature review revealed that the MRI findings of the nipple mass in our case were consistent with the common features of a schwannoma.

Keywords: Breast; Magnetic Resonance Imaging; Neurilemmoma; Nipple

DOI: https://doi.org/10.4048/jbc.2023.26.e48

BMJ Case Rep. 2023 Nov 24. pii: e256900. [Epub ahead of print]16(11):

Epithelioid malignant peripheral nerve sheath tumour of the ulnar nerve around the elbow: a diagnostic and therapeutic challenge.

Ashwath M Acharya, Anil K Bhat, Mithun Pai G, Ekanki Bansal.

Epithelioid malignant peripheral nerve sheath tumour (EMPNST) is a rare histological subtype of malignant peripheral nerve sheath tumour (MPNST), accounting for 5% to 17% of MPNSTs. The clinical and MRI findings of EMPNST mimic those of nerve abscesses, similar to the presentation in Hansen's disease. We present one such case with this kind of diagnostic dilemma. Intraoperative findings suggest a tumour changed the course of management subsequently. The development of neurological deficits postoperatively after tumour resection was a reconstructive challenge. To provide motor power and sensation through a procedure that provides a complete functional outcome for a young patient, distal nerve transfers were chosen. This provided an improvement in the quality of life and hastened the neurological recovery of the involved limb. Level of evidence: V.

Keywords: pain (neurology); pathology; peripheral nerve disease

DOI: https://doi.org/10.1136/bcr-2023-256900

Medicine (Baltimore). 2023 Nov 17. 102(46): e35891

A practical nomogram included hyperlipidemia for predicting lymph node metastasis in patients with superficial esophageal squamous cell carcinoma.

Jing Wang, Xiangji Liu, Tao Mao, Zitong Xu, Hanqing Li, Xiaoyu Li, Xuan Zhou, Yuning Chu, Minghan Ren, Zibin Tian.

To select an optimal treatment, it is crucial to evaluate the risk of lymph node metastasis (LNM) in patients with superficial esophageal squamous cell carcinoma (SESCC). The research aimed to explore more risk factors than before and construct a practical nomogram to predict LNM in patients with SESCC. We retrospectively reviewed 1080 patients diagnosed with esophageal cancer who underwent esophagectomy with lymphadenectomy between January 2013 and October 2021 at the Affiliated Hospital of Qingdao University. The clinical parameters, endoscopic features, and pathological characteristics of the 123 patients that were finally enrolled in this study were collected. The independent risk factors for LNM were determined using univariate and multivariate analyses. Using these factors, a nomogram was constructed to predict LNM. LNM was observed in 21 patients. Univariate analysis showed that the absence or presence of hypertriglyceridemia, tumor location, lesion size, macroscopic type, invasion depth, differentiation, absence or presence of lymphovascular invasion (LVI), and perineural invasion were significantly associated with LNM. According to the multivariate analysis, hypertriglyceridemia, tumors located in the lower thoracic esophagus, lesion size > 20 mm, submucosal invasion, and LVI were independent risk factors for LNM. A nomogram was established using these 5 factors. It showed good calibration and discrimination. Hypertriglyceridemia, tumors located in the lower thoracic esophagus, lesion size > 20 mm, submucosal invasion, and LVI were independent risk factors for LNM. A nomogram was constructed using these 5 factors. This model can help clinicians assess the risk of LNM in patients with SESCC for optimal treatment selection.

DOI: https://doi.org/10.1097/MD.0000000000035891